Adult-onset Rheumatoid Arthritis Research Articles

Childhood-onset rheumatoid arthritis at a tertiary hospital in Senegal, West Africa

BackgroundChildhood-onset rheumatoid arthritis (CORA), known as rheumatoid factor (RF)-positive juvenile idiopathic arthritis is a type of juvenile idiopathic arthritis that shares the same genetic factors and clinical features as adult-onset rheumatoid arthritis. In Africa, CORA hasn’t been the subject of a specific study.ObjectivesThe aim of this study is to describe the clinical features, disease activity, functional disability, and treatment of CORA at diagnosis in Senegal and compare the findings to other CORA populations.MethodsWe conducted a mixed cohort study by reviewing the medical records of patients diagnosed with CORA with an age of symptom onset < 18 years according to the 2019 PRINTO provisional criteria for RF-positive JIA from January 2020 to December 2022 at rheumatology department of Aristide Le Dantec Hospital in Dakar, Senegal. We collected demographic, clinical, paraclinical and therapeutic data. Disease activity score was assessed by DAS28-ESR and DAS28-CRP. Functional disability was assessed using Health Assessment Questionnaire (HAQ) or Childhood HAQ.ResultsA total of 21 patients were included. Eighteen (85.7%) were Females. The mean age at symptom onset was 13.0 ± 3.0 years, and at diagnosis was 16.4 ± 4.2 years. Morning stiffness, joint swelling, and joint deformities were found in 20, 18 and 13 patients respectively. Four patients had a family history of rheumatoid arthritis. Five patients had extra-articular involvement such as rheumatoid nodules. Two patients had interstitial lung disease. The biological inflammatory syndrome was found in 90% of cases. 16 of 21 (76.2%) patients had positive RF, and 18 of 20 (90%) patients had positive Anti-CCP. Seven of 12 (58.3%) patients had positive anti-nuclear antibodies. The mean DAS28-ESR was 5.7 ± 1.0. Fifteen (71.4%) patients had high disease activity (DAS28-ESR > 5.1). The mean DAS28-CRP was 5.4 ± 1.1. The median HAQ was 2.12 with a mean HAQ of 1.9. Nineteen (90.5%) patients were treated with methotrexate, while 17 (81%) had a combination of methotrexate and hydroxychloroquine. Oral prednisone was used in 17 (81%) cases. Non-steroidal anti-inflammatory drugs were used in 4 cases (19%). After 6 months of treatment, mean DAS28-CRP was 2.9.ConclusionIn our study, CORA mainly affects 13-year-old girls, characterised by high disease activity with joint deformity and significant functional impairment. Treatment is mainly based on methotrexate, prednisone and hydroxychloroquine. Further studies are needed to determine the exact clinical phenotype of this disease.

Distal Interphalangeal Joint Involvement May Be Associated with Disease Activity and Affected Joint Distribution in Rheumatoid Arthritis.

We investigated the relationship between distal interphalangeal (DIP) joint involvement and disease activity in 10,038 patients with adult-onset rheumatoid arthritis (RA). The affected joint distribution was investigated using the joint indices (JI) x, y, and z, corresponding to the upper and lower joints, and the predominance of large-joint involvement, respectively. DIP joint involvement (defined by the presence of tenderness and/or swelling in DIP joints) was present in 206 (2.1%) of 10,038 patients with RA. Patients with RA exhibiting DIP joint involvement were significantly younger, and more frequently women. DIP joint involvement was positively associated with Disease Activity Score-28 using C-reactive protein, and clinical variables related to high RA disease activity, including JIs x and y, and was negatively associated with JI z. JI x was significantly higher than JI y in RA patients with DIP joint involvement. An odds ratio analysis revealed that small-to-medium sized and upper-extremity joints ranked first, second, and fourth among the eight variables significantly associated with DIP joint involvement. The correlation coefficients revealed that small-sized and upper-extremity joints ranked first and second among the five significant variables. DIP joint involvement, albeit rare, is significantly associated with high RA disease activity with predominance of small-sized and upper-extremity joints.

Angioimmunoblastic T-cell lymphoma with fever, arthritis and skin pigmentation: A case report

Angioimmunoblastic T-cell lymphoma is a rare T-cell lymphoma. The clinical manifestations are not specific. In addition to the common clinical manifestations of lymphomas such as fever, weight loss, night sweats and lymphadenopathy, it may also have skin rashes, arthritis, multiple serous effusions, eosinophilia and other systemic inflammatory or immune symptoms. The lymphoma cells of angioimmunoblastic T-cell lymphoma originates from follicular helper T cells, and the follicular structure of lymph nodes disappears. In the tumor microenvironment, in addition to tumor cells, there are a large number of over-activated immune cells, such as abnormally activated B cells, which produce a series of systemic inflammation or immune-related symptoms. This disease is rare and difficult to diagnose. This article reports a 36-year-old female. She got fever, joint swelling and pain, skin pigmentation, accompanied by hepatomegaly, splenomegaly, lymphadenopathy, anemia and other multiple-systems manifestations. The clinical manifestations of this patient were similar to autoimmune diseases such as adult onset Still's disease, rheumatoid arthritis, and systemic sclerosis, which made the diagnosis difficult. At the beginning of the disease course, the patient got arthritis and fever. And her white blood cells were significantly increased. Adult onset Still's disease should be considered, but her multiple-systems manifestations could not be explained by adult onset Still's disease. And her arthritis of hands should be distinguished with rheumatoid arthritis. However, the patient's joint swelling could get better within 3-7 days, and there was no synovitis and bone erosion on joint imaging examination. The rheumatoid factor and anti-CCP antibody were negative. The diagnostic evidence for rheumatoid arthritis was insufficient. The patient's skin pigmentation and punctate depigmentation were similar to those of systemic sclerosis. But the patient had no Raynaud's phenomenon, and her sclerosis-related antibody was negative. The diagnostic evidence for systemic sclerosis was also insufficient. After 3 years, she was finally diagnosed with angioimmunoblastic T-cell lymphoma by lymph node biopsy aspiration. This case suggests that the clinical manifestations of angioimmunoblastic T-cell lymphoma are diverse, and some symptoms similar to immune diseases may appear. When the patient's clinical symptoms are atypical and immune diseases cannot explain the patient's condition, and further evidence should be sought to confirm the diagnosis.

THU0114 CERTOLIZUMAB PEGOL IN PATIENTS WITH RHEUMATOID ARTHRITIS: POOLED EFFICACY ANALYSIS OF PHASE 3 CLINICAL TRIALS ACROSS BASELINE RHEUMATOID FACTOR QUARTILES

Background:The presence of rheumatoid factor (RF) in patients (pts) with rheumatoid arthritis (RA) is associated with higher disease activity,1and is regarded as a risk factor for more aggressive RA.1Most studies on anti-tumour necrosis factor (TNF) monoclonal antibodies such as infliximab, etanercept and adalimumab have shown better response in pts with negative versus positive and low versus high baseline RF titres.2-3Certolizumab pegol (CZP), a PEGylated, Fc-free anti-TNF, has shown rapid and sustained reduction in signs and symptoms of moderate to severe RA, inhibition of radiographic progression and improvements in physical function in pts with an inadequate response to methotrexate (MTX).4–7The efficacy of CZP in pts with different baseline RF levels has not been studied.Objectives:To assess the efficacy of CZP, as measured by Disease Activity Score 28-erythrocyte sedimentation rate (DAS28[ESR]), in pts with active RA across baseline RF levels.Methods:In this post-hoc analysis, data were pooled from four clinical trials of CZP in RA: two global trials (RAPID 1,NCT00152386and RAPID 2,NCT00175877), a Japanese trial (J-RAPID,NCT00791999) and a Chinese trial (RAPID-C,NCT02151851). Pts ≥18 years with adult onset RA for ≥6 months (defined by ACR 1987 criteria), who received MTX for ≥6 months (≥3 months for RAPID-C) prior to baseline, were randomised 1:1 to receive placebo (PBO) every two weeks (Q2W)/CZP 400 mg Q2W/CZP 200 mg Q2W (CZP 400 mg at Weeks [Wks] 0/2/4) plus MTX for at least 24 Wks. Complete study design and pt characteristics were reported previously.4–7Here we include only pts who received CZP 200 mg Q2W (CZP 400 mg at Wks 0/2/4). RF titres were measured by validated assays in local hospital laboratories. Pts were stratified into quartiles based on pooled baseline RF levels: &lt;25.0, &lt;78.5, &lt;207.0 and ≥207.0 IU/mL. DAS28(ESR) categories were adopted to stratify pts: remission (REM), DAS28(ESR) &lt;2.6; low disease activity (LDA), DAS28(ESR) ≤3.2. Missing values were imputed using last observation carried forward.Results:Data were pooled from 1,017 and 504 pts in the CZP 200 mg Q2W and PBO Q2W groups, respectively. At baseline, mean [SD] DAS28(ESR) was similar with PBO vs CZP across RF quartiles (6.5 [0.9] – 7.0 [0.9] vs 6.6 [0.9] – 7.0 [0.9]). Compared with the PBO group, numerically higher DAS28(ESR) REM and LDA rates were observed for CZP 200 mg Q2W group at Wk 24 across RF quartiles (Figure 1). DAS28(ESR) REM and LDA responder rates increased to Wk 24 in pts treated with CZP. In general, LDA and REM rates were similar across RF quartiles at all timepoints (Figure 2).Conclusion:Over 24 Wks of treatment, trends showed steady efficacy of CZP across baseline RF quartiles in pts with active RA. In this pooled post-hoc analysis, efficacy of CZP appeared to be consistent and independent of RF levels; observed efficacy may be related to the unique molecular structure of CZP. CZP treatment in association with MTX may be a feasible option in pts with RA regardless of baseline RF status.

Comparison of Biologic Discontinuation in Patients With Elderly-Onset Versus Younger-Onset Rheumatoid Arthritis.

ObjectiveThe objective of this study is to compare biologic drug discontinuation rates for older‐ versus younger‐onset rheumatoid arthritis (YORA) because this is a key outcome measure that could impact prescribing practices.MethodsWe performed a retrospective medical record review of all patients who fulfilled the 1987 American College of Rheumatology (ACR) criteria for adult‐onset rheumatoid arthritis (RA) in 1999‐2013 among residents of a geographically defined area, with follow‐up until death, migration, or July 1, 2017. Discontinuation rates were estimated using cumulative incidence adjusted for the competing risk of death.ResultsA total of 240 cases of elderly‐onset rheumatoid arthritis (EORA) and 366 cases of YORA were identified (65% and 73% female, respectively; P = 0.025). Cumulative incidence of biologic initiation was lower among the EORA cohort compared with the YORA cohort (18% vs 33%, respectively, at 10 years after RA incidence; P < 0.001). Among those treated with a biologic, years from RA diagnosis to first biologic treatment was not significantly different between the two groups (P = 0.62). Drug survival of first biologic was 64% at 1 year (95% confidence interval [CI]: 45%‐77%) and 53% at 2 years (95% CI: 33%‐66%) for EORA, compared with 61% at 1 year (95% CI: 50%‐69%) and 45% at 2 years (95% CI: 34%‐53%) for YORA (P = 0.75). Concurrent glucocorticoid use at initiation of first biologic was statistically and significantly associated with a lower risk of discontinuation in EORA (hazard ratio 0.21; 95% CI: 0.08‐0.53) but not in YORA (interaction P = 0.04).ConclusionDrug survival rates of biologic medications did not differ significantly between patients with EORA and YORA.

Yoga-therapy for rheumatoid arthritis: Marked improvement in patient-reported outcome measures

A service evaluation study of 10 adult-onset rheumatoid arthritis (RA) participants was undertaken to determine: 1. the feasibility of providing yoga-therapy (YT) for RA in a standard consulting room 2. the impact of a 16-week YT intervention programme on outcomes of function and quality of

Orthopedic Surgery Among Patients With Rheumatoid Arthritis: A Population‐Based Study to Identify Risk Factors, Sex Differences, and Time Trends

To identify risk factors for large-joint surgery (LJS) versus small-joint surgery (SJS) in rheumatoid arthritis (RA) and evaluate trends in surgery rates over time. A retrospective medical record review of all orthopedic surgeries following first fulfillment of the 1987 American College of Rheumatology criteria for adult-onset RA among residents of Olmsted County, Minnesota between 1980 and 2013 was performed. Risk factors were examined using Cox models adjusted for age, sex, and calendar year of RA incidence. Trends in incidence of joint surgeries were examined using Poisson regression models. A total of 1,077 patients with RA (mean age 56 years, 69% female, 66% seropositive for rheumatoid factor [RF] and anti-cyclic citrullinated peptide [anti-CCP] antibodies) were followed for a median of 10.7 years, during which 112 patients (90 women) underwent at least 1 SJS and 204 (141 women) underwent at least 1 LJS. Risk factors included advanced age, and RF and anti-CCP antibody positivity for both SJS and LJS, and body mass index ≥30 kg/m2 for LJS. Risk factors for SJS and LJS at any time during followup included the presence of radiographic erosions, large-joint swelling, and methotrexate use. SJS rates decreased by calendar year of incidence (hazard ratio 0.53, P = 0.001), with significant decline in the rates of SJS after 1995. The cumulative incidence of SJS was higher in women than men (P = 0.008). In recent years, there has been a significant decline in the rates of SJS but not LJS in patients with RA. The incidence of SJS is higher among women. Traditional RA risk factors are strong predictors for SJS and LJS. Increasing age and obesity are predictive of LJS.

Baricitinib in Patients with Rheumatoid Arthritis and an Inadequate Response to Conventional Disease-Modifying Antirheumatic Drugs in United States and Rest of World: A Subset Analysis

This article evaluates the efficacy and safety of baricitinib 4mg versus placebo in United States including Puerto Rico (US) and rest of the world (ROW) subpopulations using data pooled from RA-BEAM and RA-BUILD, which enrolled patients with moderate-to-severe adult-onset rheumatoid arthritis (RA). In RA-BEAM, patients with an inadequate response (IR) to methotrexate, at least one X-ray erosion, and high sensitivity C-reactive protein (hsCRP) ≥ 6mg/L were randomized to placebo or orally administered baricitinib 4mg daily or subcutaneously administered adalimumab 40mg every other week. In RA-BUILD, patients with an IR to at least one conventional synthetic disease-modifying antirheumatic drug (csDMARD) and with hsCRP ≥ 3.6mg/L were randomized to placebo or baricitinib 2 or 4mg daily. Patients in both trials were biologic naive. In this post hoc analysis, data from both studies were pooled (714 baricitinib 4mg-treated, 716 placebo-treated patients). Overall, 188 US and 1242 ROW patients were included. Subgroups differed in baseline characteristics including race, weight, age, time since RA diagnosis, current corticosteroid use, and previous csDMARD use. At weeks 12 and 24, baricitinib-treated patients had larger responses compared to placebo-treated patients for multiple efficacy outcomes: American College of Rheumatology 20/50/70 response, low disease activity, remission, Disease Activity Score 28-C-reactive protein, and Health Assessment Questionnaire-Disability Index. Overall, similar efficacy was observed in US and ROW subgroups with no notable safety differences between subgroups at weeks 12 or 24. Baricitinib 4mg was efficacious compared to placebo in US and ROW subpopulations. Safety was similar between subgroups. Eli Lilly & Company and Incyte Corporation. ClinicalTrials.gov identifiers, NCT01721057; NCT01710358.

Single nucleotide polymorphism of Methyl-CpG-binding protein 2 gene associates with juvenile idiopathic arthritis.

Methyl-CpG-binding protein 2 (MeCP2) is a transcription suppressor or activator, acting through binding to methylated DNA. Numerous investigations have established a role for methylation aberrancies in the pathogenesis of autoimmune disorders. Single nucleotide polymorphisms (SNPs) in MECP2 gene have been implicated with susceptibility to rheumatoid arthritis (RA). Here, the plausible association of MECP2 gene polymorphisms was evaluated with juvenile idiopathic arthritis (JIA) predisposition in Iranian pediatric patients. In this case-control association study, 49 JIA patients and 398 age-, sex-, and ethnicity-matched healthy individuals were included. Genotyping of all samples for MECP2 gene rs1734787, rs1734791, rs1734792, and rs17435 polymorphisms was conducted by real-time allelic discrimination PCR technique. Except the AT genotype of rs17435 SNP, none of the alleles and genotypes of other positions were distributed significantly between JIA cases and controls. AT genotype was less frequent in JIA cases and was found to be protective genotype of JIA proneness (OR = 0.42; CI, 0.19-0.90; P = 0.028). Among the haplotypes, CCAA and TTTT were detected to have significant difference between cases and controls (OR = 1.74; CI, 1.01-2.98; P = 0.042 and OR = 1.82; CI, 1.05-3.13; P = 0.028). All positions were in linkage disequilibrium with each other according to D'. MECP2 gene rs17435 polymorphism was associated with JIA predisposition. Considering the involvement of genetic polymorphisms of MECP2 gene in susceptibility to adult-onset RA, this gene might basically play a role in the initiation of arthritis during early stages of life.

Childhood Residential and Agricultural Pesticide Exposures in Relation to Adult-Onset Rheumatoid Arthritis in Women.

Farming and pesticide exposure may influence risk of rheumatoid arthritis (RA); the role of early-life pesticide exposure is unknown. The Sister Study includes a US national cohort of women aged 35-74 years (enrolled 2004-2009); we examined childhood pesticide exposure in women in this cohort with adult-onset RA. Cases (n = 424) were compared with 48,919 noncases. Data included pesticide use at the longest childhood residence through age 14 years, farm residence of at least 12 months with agricultural pesticide exposure through age 18 years, and maternal farm experience. Odds ratios and 95% confidence intervals were adjusted for age, race or ethnicity, education, smoking, and childhood socioeconomic factors. Cases with RA reported more frequent and direct (personal) residential pesticide use in childhood (for infrequent/indirect pesticide use, odds ratio (OR) = 1.1; for frequent/direct use, OR = 1.8; P for trend = 0.013). Compared with women without residential farm history, odds of having RA increased for those reporting a childhood-only farm residence with personal exposure to pesticides used on crops (OR = 1.8, 95% confidence interval: 1.1, 2.9) or livestock (OR = 2.0, 95% confidence interval: 1.2, 3.3). Our findings suggest adult-onset RA may be related to childhood exposure to residential and agricultural pesticides, and support further investigations of lifetime pesticide use in RA.

A novel subset of fibrocyte-like cells in synovial fluid communicate with CD8 T cells and shape the local inflammatory milieu in Juvenile Idiopathic Arthritis (JIA). (HUM3P.253)

Abstract We reported previously that children with JIA carry senescent CD31+CD8+ T cells disproportionate with age. Such cells are inflammatory effectors via CD31-driven TCR-independent activation pathway. Here, we hypothesized that these T cells interact with non-hematopoietic cells in the synovial space to perpetuate joint inflammation. JIA patients medically indicated to undergo arthrocentesis were recruited. Synovial aspirates were screened by flow cytometry, and short-term cultures were established. Results showed two subsets of plastic-adherent fibrocyte-like cells (FLC). About 75% were procollagen-CD45-CD14- cells that variably expressed CD34. The other ~25% were procollagen+CD45+CD14+IL17RA+ CD34- FLC; a finding unlike similar cells reported for adult-onset rheumatoid arthritis. FLC exposed to rIL-17 and/or rTNFα induced production of MMPs that were reversed with corticosteroid, TNFi, anti-IL6R, or experimental NFkB inhibitors. Co-culture of FLC with autologous CD8 T cells resulted in production of the same array of MMPs and inflammatory cytokines that were partially blocked by neutralizing anti-CD31 antibody. These results suggest a FLC-CD8 T cell communication circuit in the maintenance of joint inflammation in JIA. Further understanding of the regulation and/or the consequences of this local cell-cell interaction could shed light into the systemic complications of this childhood disease that impose lifelong health burden. [Supported by Nancy E Taylor Foundation and NIH].

A109: Insufficient CARRA Registry Data Available to Adequately Evaluate for Associations Between Juvenile Idiopathic Arthritis, Antibody Status, and Smoke Exposure

Background/Purpose:The CARRA registry was established as a means to further investigate potential associations as well as better understand manifestations of pediatric rheumatic disease. The most frequent diagnosis in the registry is Juvenile Idiopathic Arthritis/Juvenile Ankylosing Spondylitis (JIA/JAS). An association between smoking and adult onset rheumatoid arthritis has long been established through epidemiologic studies. We hypothesized that patients with seropositive JIA, with either rheumatoid factor antibody against Fc portion of IgG or antibodies against citrullinated proteins (APCA) have higher rates of passive and/or active smoking exposure compared to patients that lack such abs including other rheumatic disease and Juvenile Primary Fibromyalgia Syndrome (JFPS).Methods:The CARRA registry was used to identify subjects with JIA/JAS, their APCA and RF status. Smoke exposure included any smoking (AS), as well as individual childhood smoking (CC) and household second hand smoke (HH). Using logistic regression smoke exposure rates were compared between subjects with and without JIA/JAS . Subjects with a diagnosis of JPFS, served as a non rheumatic disease control group. APCA and RF were compared between JIA/JAS according to smoking status and other disease populations in the registry.Results:In 2351 CARRA registry subjects for whom CC data was available, 38 smoked, resulting in an incidence of 1.6%. However, 7099 subjects had missing data (75%) regarding CC. Case control analysis did not show differences in CC in JIA compared to other pediatric rheumatic disease in the registry. Of 1512 subjects without HH, 372 (24.6%) had APCA status recorded and 691 (45.7%) had RF status recorded. Of 247 subjects with HH, 65 (26.3%) had APCA status recorded and 114 (46.2%) had RF status obtained. Interestingly there no JPFS subjects (0/605 with CC exposure. Significant risk was not found between overall smoke exposures in JIA subjects (172/1135; 15%) compared with JPFS controls (10/57; 17%). The extent to which missing data, especially with regard to HH status, contributed to the lack of demonstrable association of JIA/JAS and smoking is unknown.Conclusion:Traditional teaching in pediatric rheumatology is that measurement of RF is not useful for JIA diagnosis in children less than age ten, especially when disease is oligoarticular in onset, however consensus guidance regarding the routine measurement of APCA has not yet been established. Seropositive JIA patient numbers and those whom have had adequate ascertainment of smoking exposure are lacking in the current CARRA registry, inhibiting the analysis in this environmental epidemiology study. More complete ascertainment of smoke exposure history should be possible for those subjects remaining in the registry even though error due to recall bias may occur. There also remains an important role for initiating baseline sample collection at entry into the CARRA registry for future studies set to determine environmental/epigenetic contributions to JIA.

Hyperuricemia and incident cardiovascular disease and noncardiac vascular events in patients with rheumatoid arthritis.

Objective. To evaluate whether hyperuricemia is a risk factor for cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA). Methods. A population-based inception cohort of patients diagnosed between 1980 and 2007 with adult-onset RA was assembled. A comparison cohort of age- and sex-matched subjects without RA (non-RA) was also assembled. All clinically obtained uric acid values were collected. CVD and noncardiac vascular events were recorded for each patient. Cox proportional hazards models were used to assess the impact of hyperuricemia on development of CVD, mortality, and noncardiac vascular disease. Results. In patients without RA, hyperuricemia was associated with heart failure (HR: 1.95; 95% CI: 1.13–3.39) and CVD (HR: 1.59; 95% CI: 0.99–2.55). In patients with RA, hyperuricemia was not significantly associated with CVD but was significantly associated with peripheral arterial events (HR: 2.52; 95% CI: 1.17–5.42). Hyperuricemia appeared to be more strongly associated with mortality among RA patients (HR: 1.96; 95% CI: 1.45–2.65) than among the non-RA subjects (HR: 1.57; 95% CI: 1.09–2.24). Conclusion. In patients with RA, hyperuricemia was a significant predictor of peripheral arterial events and mortality but not of CVD.

Development of Reduced Kidney Function in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is associated with a variety of kidney disorders. However, it is unclear whether the development of reduced kidney function is higher in patients with RA compared to the general population. Retrospective review. Incident adult-onset RA cases (813) and a comparison cohort of non-RA individuals (813) in Olmsted County, MN, in 1980-2007. Baseline demographic and clinical variables. Reduced kidney function: (1) estimated glomerular filtration rate (eGFR)<60mL/min/1.73m(2) and (2) eGFR<45mL/min/1.73m(2) on 2 consecutive occasions at least 90 days apart; cardiovascular disease (CVD); and death. The cumulative incidence of reduced kidney function was estimated adjusting for the competing risk of death. Of 813 patients with RA and 813 non-RA individuals, mean age was 56±16 (SD) years, 68% were women, and 9% had reduced kidney function at baseline. The 20-year cumulative incidence of reduced kidney function was higher in patients with RA compared with non-RA participants for eGFR < 60mL/min/1.73m(2) (25% vs 20%; P=0.03), but not eGFR<45mL/min/1.73m(2) (9% vs 10%; P=0.8). The presence of CVD at baseline (HR, 1.77; 95% CI, 1.14-2.73; P=0.01) and elevated erythrocyte sedimentation rate in patients with RA (HR per 10-mm/h increase, 1.08; 95% CI, 1.00-1.16; P=0.04) was associated with increased risk of eGFR<60mL/min/1.73m(2). eGFR<60mL/min/1.73m(2) was not associated with increased risk of CVD development in patients with RA (HR, 0.99; 95% CI, 0.63-1.57; P=0.9), however, a greater reduction in GFR (eGFR<45mL/min/1.73m(2)) was associated with increased risk of CVD (HR, 1.93; CI, 1.04-3.58; P=0.04). Reduced kidney function was defined by estimating equations for kidney function. We are limited to deriving associations from our findings. Patients with RA were more likely to develop reduced kidney function over time. CVD and associated factors appear to play a role. The presence of RA in individuals with reduced kidney function may lead to an increase in morbidity from CVD development, for which awareness may provide a means for optimizing care.

AB0711 Polymyalgia rheumatica: is it under-represented at rheumatology conferences?

BackgroundPolymyalgia Rheumatica (PMR) has been cited as the commonest inflammatory rheumatological disorder in the over 50s with a life time prevalence of 2.4% in females & 1.7% in males1. In...

Susceptibility to childhood-onset rheumatoid arthritis: investigation of a weighted genetic risk score that integrates cumulative effects of variants at five genetic loci.

Children with childhood-onset rheumatoid arthritis (RA) include those with rheumatoid factor or anti-citrullinated protein antibody-positive juvenile idiopathic arthritis. To test the hypothesis that adult-onset RA-associated variants are also associated with childhood-onset RA, we investigated RA-associated variants at 5 loci in a cohort of patients with childhood-onset RA. We also assessed the cumulative association of these variants in susceptibility to childhood-onset RA using a weighted genetic risk score (wGRS). A total of 155 children with childhood-onset RA and 684 healthy controls were genotyped for 5 variants in the PTPN22, TRAF1/C5, STAT4, and TNFAIP3 loci. High-resolution HLA-DRB1 genotypes were available for 149 cases and 373 controls. We tested each locus for association with childhood-onset RA via logistic regression. We also computed a wGRS for each subject, with weights based on the natural log of the published odds ratios (ORs) for the alleles investigated, and used logistic regression to test the wGRS for association with childhood-onset RA. Childhood-onset RA was associated with TNFAIP3 rs10499194 (OR 0.60 [95% confidence interval 0.44-0.83]), PTPN22 rs2476601 (OR 1.61 [95% confidence interval 1.11-2.31]), and STAT4 rs7574865 (OR 1.41 [95% confidence interval 1.06-1.87]) variants. The wGRS was significantly different between cases and controls (P < 2 × 10(-16) ). Individuals in the third to fifth quintiles of wGRS had a significantly increased disease risk compared to baseline (individuals in the first quintile). Higher wGRS was associated with increased risk of childhood-onset RA, especially among males. The magnitude and direction of the association between TNFAIP3, STAT4, and PTPN22 variants and childhood-onset RA are similar to those observed in RA, suggesting that adult-onset RA and childhood-onset RA share common genetic risk factors. Using a wGRS, we have demonstrated the cumulative association of RA-associated variants with susceptibility to childhood-onset RA.

Dietary intake of vitamin D during adolescence and risk of adult‐onset systemic lupus erythematosus and rheumatoid arthritis

Vitamin D has immunomodulatory properties with potential etiologic implications for autoimmune diseases. The relevant exposure time during which vitamin D may influence disease risk is unknown. Our objective was to examine the relationship between reported vitamin D intake during adolescence and adult-onset rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) incidence in prospective cohort studies of women, the Nurses' Health Study (NHS) and the Nurses' Health Study II (NHSII). Food frequency questionnaires concerning high school diet completed by 73,629 NHS (1986) and 45,544 NHSII (1998) participants were used to calculate nutrient intakes during adolescence. Incident RA and SLE cases prior to 2006 (NHS) and 2007 (NHSII) were confirmed by medical record review. Cox proportional hazards models calculated relative risks and 95% confidence intervals of incident RA and SLE according to quintile cutoffs of vitamin D intake. Age- and calorie-adjusted and multivariable-adjusted (including sun exposure factors) analyses were completed. Random-effects models were used to meta-analyze estimates of association from the 2 cohorts. Incident RA was confirmed in 652 NHS and 148 NHSII participants and SLE was confirmed in 122 NHS and 54 NHSII participants over a mean followup time of 351 months (NHS) and 209 months (NHSII). Age- and calorie-adjusted and multivariable-adjusted models did not show significant associations between adolescent vitamin D intake and risk of adult-onset RA or SLE. We did not find associations between adolescent dietary vitamin D intake and adult RA or SLE risk among NHS and NHSII women, suggesting that other time periods during the life course should be studied.

Dietary intake of vitamin D during adolescence and risk of adult onset systemic lupus erythematosus and rheumatoid arthritis

Dietary intake of vitamin D during adolescence and risk of adult onset systemic lupus erythematosus and rheumatoid arthritis

Incidence of progressive multifocal leukoencephalopathy in patients with rheumatoid arthritis: a national population-based study

BackgroundCases of progressive multifocal leukoencephalopathy (PML), a rare but serious disease, have been reported in patients with rheumatoid arthritis (RA) in association with biological therapy, but little is known about...

Acute Atraumatic Hip Dislocation in an Adult with Rheumatoid Arthritis

There are no reports of atraumatic hip subluxation and dislocation in the adult patient with rheumatoid arthritis (RA). This rare phenomenon is most prevalent in patients with congenital hip dislocation, von Recklinghausen disease, tumor infiltration, connective tissue disorders, and juvenile rheumatoid arthritis. We report an acute atraumatic dislocation of the hip in an adult patient with RA. We believe that two factors contributed to the patient's atraumatic dislocation: a shallow but appropriately positioned acetabulum and erosive RA with substantiate panus formation. Similar to previous reports, there was a rent or capsular defect that may have contributed to the mechanism of dislocation. Physicians should be aware that, although rare, a de novo atraumatic hip dislocation is a possibility in a patient with a long-standing history of RA and hip pain. Distinguishing features of this case include the acuteness of the dislocation, the absence of previous symptoms, and adult-onset RA.