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ObjectivesTo prospectively investigate differences in medium-term patient-reported outcome measures and objective functional outcome measures, between patients receiving and those not receiving intensive short-term immunosuppressive therapy for coronavirus disease 19 (COVID-19)-associated hyperinflammation.MethodsPatients previously included in the COVID-19 High-intensity Immunosuppression in Cytokine storm syndrome (CHIC) study who received immunosuppressive treatment versus standard of care for COVID-19-associated hyperinflammation were invited for follow-up at 3 and 6 months after hospitalisation. At both visits, patients were assessed by a pulmonologist, completed quality of life (QoL) questionnaires and performed pulmonary and exercise function tests. At 3 months, patients additionally completed questionnaires on dyspnoea, anxiety, depression and trauma. Outcomes were compared between patients receiving and those not receiving intensive short-term immunosuppressive therapy for COVID-19-associated hyperinflammation.Results131 (66.5%) patients survived hospitalisation due to COVID-19-associated hyperinflammation and 118 (90.1%) were included. QoL questionnaires, pulmonary- and exercise function tests showed improvement between 3 and 6 months after discharge, which was similar in both groups. Assessed patients reached levels that were close to levels predicted from the normal population. In contrast, diffusing capacity of the lung for carbon monoxide was disturbed in both groups: 69.6% predicted (SD 16.2) and 73.5% predicted (SD 16.5) in control group and treated group, respectively.ConclusionsNo differences in medium-term outcomes are demonstrated in survivors of COVID-19-associated hyperinflammation treated or not treated with methylprednisolone with or without tocilizumab during the acute phase. Short-term benefits of this therapy, as showed in the baseline CHIC study analysis, are thus not hampered by medium-term adverse events.

Objectives COVID-19 is an ongoing global pandemic. There is an urgent need for identification and understanding of clinical and laboratory parameters related to progression towards a severe and fatal form of this illness, often preceded by a so-called cytokine-storm syndrome (CSS). Therefore, we explored the hemocytometric characteristics of COVID-19 patients in relation to the deteriorating clinical condition CSS, using the Sysmex XN-10 hematology analyzer. Methods From March 1st till May 16th, 2020, all patients admitted to our hospital with respiratory complaints and suspected for COVID-19 were included (n=1,140 of whom n=533 COVID-19 positive). The hemocytometric parameters of immunocompetent cells in peripheral blood (neutrophils [NE], lymphocytes [LY] and monocytes [MO]) obtained upon admission to the emergency department (ED) of COVID-19 positive patients were compared with those of the COVID-19 negative ones. Moreover, patients with CSS (n=169) were compared with COVID-19 positive patients without CSS, as well as with COVID-19 negative ones. Results In addition to a significant reduction in leukocytes, thrombocytes and absolute neutrophils, it appeared that lymphocytes-forward scatter (LY-FSC), and reactive lymphocytes (RE-LYMPHO)/leukocytes were higher in COVID-19-positive than negative patients. At the moment of presentation, COVID-19 positive patients with CSS had different neutrophils-side fluorescence (NE-SFL), neutrophils-forward scatter (NE-FSC), LY-FSC, RE-LYMPHO/lymphocytes, antibody-synthesizing (AS)-LYMPHOs, high fluorescence lymphocytes (HFLC), MO-SSC, MO-SFL, and Reactive (RE)-MONOs. Finally, absolute eosinophils, basophils, lymphocytes, monocytes and MO-FSC were lower in patients with CSS. Conclusions Hemocytometric parameters indicative of changes in immunocompetent peripheral blood cells and measured at admission to the ED were associated with COVID-19 with and without CSS.

This work was funded by European League Against Rheumatism (CLI122). PMM is supported by the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre (BRC). JDI is a NIHR Senior Investigator and his work is supported by the NIHR Newcastle Biomedical Research Centre in Ageing and Long- Term Conditions, and the Research Into Inflammatory Arthritis Centre versus Arthritis. AVR is a member of the paediatric steering committee of RECOVERY, the steering committee of COVINTOC study and the steering committee of baricitinib in COVID-19., Alunno, A., Najm, A., MacHado, P.M., Bertheussen, H., Burmester, G.R., Carubbi, F., De Marco, G., Giacomelli, R., Hermine, O., Isaacs, J.D., Koné-Paut, I., Magro-Checa, C., McInnes, I., Meroni, P.L., Quartuccio, L., Ramanan, A.V., Ramos-Casals, M., Carrio, J.R., Schulze-Koops, H., Stamm, T.A., Tas, S.W., Terrier, B., McGonagle, D.G., Mariette, X.

Several immune mechanisms resembling a hyperinflammatory state have been critically involved in the pathophysiology of severe COVID-19, motivating the use of immunomodulatory therapies in the management of these patients. Various studies have already suggested the efficacy of immunomodulatory medication of treatment for severe COVID-19.1–3 However, concerns have been raised about the impact of these therapies on immunity.4 5 We analysed the presence and levels of antibodies to SARS-CoV-2 in patients recovered from severe COVID-19-associated hyperinflammation after receiving no immunomodulatory therapy, and compared them to patients who received methylprednisolone alone or methylprednisolone followed by tocilizumab. Between March and May 2020, 197 patients were diagnosed with COVID-19-associated hyperinflammation in the Zuyderland Medical Centre. In order to meet the criteria for hyperinflammation, patients had to fulfil specific characteristics that have been previously reported in this journal.1 Up to the 1st of April, patients were treated with standard of care. In April and May, patients were treated according to the COVID-19 high-intensity immunosuppression in cytokine storm syndrome (CHIC) protocol with immunomodulatory therapies. This protocol included …

Background New ACR-EULAR SLE criteria have been proposed in order to attempt to improve classification for clinical and translational research (1, 2). Objectives We evaluated the performance of the proposed 2017 ACR-EULAR classification criteria in a cohort of SLE patients with neuropsychiatric (NP) symptoms and compared to previous classification criteria. Methods Medical records of patients visiting the NPSLE clinic of the Leiden University Medical Center (LUMC) between 2007-2017 were retrospectively evaluated. The performance of the proposed 2017 ACR-EULAR criteria, the 2012 SLICC criteria and the 1997 ACR criteria was evaluated by calculating sensitivity and specificity. Results 360 patients were included, of which 294 were clinically diagnosed with SLE. The newly proposed 2017 ACR-EULAR showed a sensitivity of 87% (95% CI: 83-91%) and a specificity of 74% (95% CI: 62-84%), as shown in Table 1. The 2012 SLICC criteria had a sensitivity of 85% (95% CI: 80-89%) and a specificity of 76% (95% CI: 64-85%). The 1997 ACR criteria had a sensitivity of 89% (95% CI: 85-92%) and a specificity of 89% (95% CI: 80-96%). Sixty out of 294 patients fulfilled the proposed NP domain (delirium/psychosis/epilepsy). Using more specific criteria for NP symptoms related to SLE, as previously proposed by Bortoluzzi et al. (3), only 37 patients fulfilled this domain. However, this did not improve specificity, which remained 74% (95% CI: 62-84%). In addition, the performance of the newly proposed criteria was evaluated including patients with more than 10 points, but negative ANA. This led to an increase of sensitivity to 90% (95% CI 86-94%), but also did not influence specificity. Conclusion In a cohort of SLE patients with NP symptoms, the proposed 2017 ACR-EULAR classification criteria showed similar sensitivity as the 1997 ACR and the SLICC 2012 criteria, but lower specificity. Including ANA negative patients improved sensitivity. References [1] 2018ACR/ARHP Annual Meeting Abstract Supplement. Arthritis Rheumatol, 2018.70Suppl 9: p.1-355. [2] Tedeschi SK, et al., Developing and Refining New Candidate Criteria for Systemic Lupus Erythematosus Classification: An International Collaboration. Arthritis Care Res (Hoboken), 2018. 70(4): p.571-581. [3] Bortoluzzi A, et al., Development and validation of a new algorithm for attribution of neuropsychiatric events in systemic lupus erythematosus. Rheumatology (Oxford), 2015. 54(5): p.891-8. Disclosure of Interests Rory Monahan: None declared, H.J.L. Beaart: None declared, Maka Gegeneva: None declared, E.G. Brilman: None declared, L.J.J. Beaart- van de Voorde: None declared, Cesar Magro Checa: None declared, Thomas Huizinga Consultant for: Merck, UCB, Bristol Myers Squibb, Biotest AG, Pfizer, GSK, Novartis, Roche, Sanofi-Aventis, Abbott, Crescendo Bioscience Inc., Nycomed, Boeringher, Takeda, Zydus, Epirus, Eli Lilly, G.M. Steup-Beekman: None declared

Objective: Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that have similar clinical and immunologic characteristics. To date, several shared SSc–RA genetic loci have been identified independently. The aim of the current study was to systematically search for new common SSc–RA loci through an interdisease meta–genome-wide association (meta-GWAS) strategy. Methods: The study was designed as a meta-analysis combining GWAS data sets of patients with SSc and patients with RA, using a strategy that allowed identification of loci with both same-direction and opposite-direction allelic effects. The top single-nucleotide polymorphisms were followed up in independent SSc and RA case–control cohorts. This allowed an increase in the sample size to a total of 8,830 patients with SSc, 16,870 patients with RA, and 43,393 healthy controls. Results: This cross-disease meta-analysis of the GWAS data sets identified several loci with nominal association signals (P < 5 × 10−6) that also showed evidence of association in the disease-specific GWAS scans. These loci included several genomic regions not previously reported as shared loci, as well as several risk factors that were previously found to be associated with both diseases. Follow-up analyses of the putatively new SSc–RA loci identified IRF4 as a shared risk factor for these 2 diseases (Pcombined = 3.29 × 10−12). Analysis of the biologic relevance of the known SSc–RA shared loci identified the type I interferon and interleukin-12 signaling pathways as the main common etiologic factors. Conclusion: This study identified a novel shared locus, IRF4, for the risk of SSc and RA, and highlighted the usefulness of a cross-disease GWAS meta-analysis strategy in the identification of common risk loci.

OBJECTIVE To assess white matter (WM) and gray matter (GM) magnetization transfer ratio histogram peak heights (MTR-HPHs) in different subsets of patients with neuropsychiatric systemic lupus erythematosus (NPSLE) who have unremarkable findings on 3T magnetic resonance imaging of the brain and to evaluate whether these values could be used to highlight different clinically suspected underlying pathogenic processes or identify the clinical NPSLE status or whether they could be associated with a specific NPSLE syndrome. METHODS Sixty-four SLE patients with neuropsychiatric symptoms were included. The initial NPSLE diagnosis and suspected underlying pathogenic process were established by multidisciplinary evaluation. The final diagnosis was made after also considering the disease course 6-18 months later. Thirty-three patients with central nervous system (CNS) NPSLE and 31 SLE patients with neuropsychiatric symptoms unrelated to SLE (non-SLE-related NP) were included. Twenty SLE patients without neuropsychiatric symptoms and 36 healthy control subjects were included for comparison. Differences in the WM and GM mean MTR-HPHs and between the different NPSLE subgroups (CNS NPSLE diagnosis, NPSLE phenotype [inflammatory or ischemic], and clinical changes after treatment) and the relationship to NPSLE syndromes were evaluated. RESULTS Patients with inflammatory NPSLE had significantly lower WM MTR-HPHs than did the healthy controls, the SLE patients, and the non-SLE-related NP patients. Cognitive disorder, mood disorder, and psychosis were related to lower WM MTR-HPH values and cerebrovascular symptoms to higher values. Furthermore, the mean MTR-HPHs in the WM increased when the clinical status of the NPSLE patients improved. CONCLUSION Measurement of MTR-HPH of the WM has the potential to identify inflammatory NPSLE with CNS involvement. This finding underscores the usefulness of this technique for the detection of cerebral changes in NPSLE patients and for the assessment of clinical changes after treatment.

Key messages #### What is already known about this subject? #### What does this study add? #### How might this impact on clinical practice? Systemic lupus erythematosus (SLE) is a heterogenic connective tissue disease with a broad spectrum of clinical and laboratory manifestations. Due to this heterogeneity, SLE remains challenging to diagnose in clinical practice. In order to create a more homogeneous patient group, the American College of Rheumatology (ACR) developed classification criteria for research purposes in 1972.1 These criteria were revised in 1982 and 1997.2 3 In 2012, the Systemic Lupus International Collaborating Clinics (SLICC) developed and validated new SLE classification criteria.4 The SLICC 2012 criteria performed better than the revised 1997 ACR criteria in terms of sensitivity (97% vs 83%), but were less specific (84% vs 96%).4 Recently, new ACR–EULAR criteria have been proposed in order to improve specificity, while keeping the optimal sensitivity of the SLICC 2012 criteria. Several new elements were added, including the presence of antinuclear antibodies (ANA) as entry criterium, weighted scores for each criterium and domain scores.5–7 It is currently unknown how these criteria perform in patients with SLE with neuropsychiatric (NP) symptoms, one of the least understood manifestations of SLE. Therefore, we aimed to evaluate the performance of the proposed ACR–EULAR criteria in our cohort of patients with SLE presenting with NP symptoms. A retrospective cohort study was performed using electronic medical records of patients referred to the NPSLE clinic in the Leiden …

Research in rheumatoid arthritis (RA) is increasingly focused on the discovery of biomarkers that could enable personalized treatments. The genetic biomarkers associated with the response to TNF inhibitors (TNFi) are among the most studied. They include 12 SNPs exhibiting promising results in the three largest genome-wide association studies (GWAS). However, they still require further validation. With this aim, we assessed their association with response to TNFi in a replication study, and a meta-analysis summarizing all non-redundant data. The replication involved 755 patients with RA that were treated for the first time with a biologic drug, which was either infliximab (n = 397), etanercept (n = 155) or adalimumab (n = 203). Their DNA samples were successfully genotyped with a single-base extension multiplex method. Lamentably, none of the 12 SNPs was associated with response to the TNFi in the replication study (p > 0.05). However, a drug-stratified exploratory analysis revealed a significant association of the NUBPL rs2378945 SNP with a poor response to etanercept (B = -0.50, 95% CI = -0.82, -0.17, p = 0.003). In addition, the meta-analysis reinforced the previous association of three SNPs: rs2378945, rs12142623, and rs4651370. In contrast, five of the remaining SNPs were less associated than before, and the other four SNPs were no longer associated with the response to treatment. In summary, our results highlight the complexity of the pharmacogenetics of TNFi in RA showing that it could involve a drug-specific component and clarifying the status of the 12 GWAS-drawn SNPs., This work was supported by the Instituto de Salud Carlos III (ISCIII, Spain) through grants PI14/01651, PI17/01606 and RD16/0012/0014 to AG and PI12/01909 to JJG-R. These grants are partially financed by the European Regional Development Fund of the EU (FEDER). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Background The diagnosis and treatment of neuropsychiatric systemic lupus erythematosus (NPSLE) is challenging due to the lack of a diagnostic gold standard and controlled trials. Immunosuppressive therapy is prescribed for immune-mediated NPSLE manifestations, despite little evidence supporting its effectivity. There is increasing evidence for the value of magnetization transfer imaging (MTI) in NPSLE. Recent research has demonstrated that white matter (WM) magnetic transfer ratio histogram peak height (MTR-HPH), a derived-MTI index, is a valuable radiological biomarker for the diagnosis and follow-up in inflammatory NPSLE.1 It remains unknown whether the changes in WM MTR-HPH also correlate with the change in health-related quality of life (QoL) in these patients. Objectives To analyse the correlation between change in WM MTR-HPH and change in QoL in different subsets of NPSLE (inflammatory, ischaemic, non-NPSLE). Methods Patients that visited the Leiden University Medical Centre (LUMC) NPSLE clinic between 2007 and 2015 were included in this study. The attribution process of NP events to SLE and one of its underlying pathogenic mechanisms (ischaemic or inflammatory) was established by multidisciplinary consensus. All patients underwent MRI examination at two different time points and filled in the Short-Form 36 (SF-36). Summary scores were deducted from the SF-36, leading to a Physical Component subscore (PCS) and a Mental Component subscore (MCS) for QoL. Spearman rank correlation coefficient (SR) was used to correlate WM MTR-HPH and the overall difference in change between visits in MCS and PCS. Data was analysed per patient and per event. Results A total of 15 patients (mean age 39.5±14.1 years, 93% female) were included. Thirty-one NPSLE events were present, of which 68% were inflammatory, 13% ischaemic and 19% non-NPSLE events. Average time between visits was 2.9±1.5 years. The per patient analysis showed statistical significant correlation between WM MTR-HPH and MCS change (SR=0.62; p=0.01) and no effect on PCS change (SR=0.09; p=0.76). The per event analysis showed a significant correlation between change in WM MTR-HPH and MCS in inflammatory events (SR=0.56; p=0.01), but not in ischaemic (p=0.20) or non-NPSLE events (p=0.65). No correlation was observed between change in WM MTR-HPH and PCS in any of the subsets (p=0.21, p=0.40 and p=0.91 respectively). Conclusions We are the first to demonstrate a correlation between a radiological biomarker and change in the mental component of QoL in inflammatory NPSLE patients. Our study supplies evidence for the use of immunosuppressive therapy in inflammatory NPSLE and supports the use of this radiological biomarker as an outcome measure for future trials in NPSLE. Reference [1] Magro-Checa C, Ecran E, Wolterbeek R, et al. Changes in White Matter Microstructure Suggest an Inflammatory Origin of Neuropsychiatric Systemic Lupus Erythematosus.Arthritis Rheumatol2016;68(8):1945–1954. Disclosure of Interest None declared

Objective The objective of this study was to assess whether clinical and patient’s reported outcomes are associated with a different pathophysiological origin of neuropsychiatric events presenting in systemic lupus erythematosus. Methods A total of 232 neuropsychiatric events presenting in 131 systemic lupus erythematosus patients were included. Neuropsychiatric systemic lupus erythematosus diagnosis was established per event by multidisciplinary evaluation. All neuropsychiatric events were divided according to a suspected underlying pathophysiological process into one of the following: non-neuropsychiatric systemic lupus erythematosus related, inflammatory and ischaemic neuropsychiatric systemic lupus erythematosus. The clinical outcome of all neuropsychiatric events was determined by a physician-completed four-point Likert scale. Health-related quality of life was measured with the subscales of the patient-generated Short Form 36 (SF-36) health survey questionnaire. The change between scores at paired visits of all domain scores, mental component summary (SF-36 MCS) and physical component summary (SF-36 PCS) scores were retrospectively calculated and used as patient-reported outcome. The association among these outcomes and the different origin of neuropsychiatric events was obtained using multiple logistic regression analysis. Results The clinical status of 26.8% non-neuropsychiatric systemic lupus erythematosus events, 15.8% ischaemic neuropsychiatric systemic lupus erythematosus and 51.6% inflammatory neuropsychiatric systemic lupus erythematosus improved after re-assessment. Almost all SF-36 domains had a positive change at re-assessment in all groups independently of the origin of neuropsychiatric events. Neuropsychiatric systemic lupus erythematosus ( B = 0.502; p Conclusion Inflammatory neuropsychiatric systemic lupus erythematosus events have better clinical outcome and meaningful improvement in SF-36 MCS than ischaemic neuropsychiatric systemic lupus erythematosus or non-neuropsychiatric systemic lupus erythematosus.

BACKGROUND: Articular manifestations are common in systemic lupus erythematosus (SLE) whereas erosive disease is not. Antibodies to cyclic citrullinated peptide (anti-CCP) are citrulline-dependent in rheumatoid arthritis (RA), whereas the opposite is suggested in SLE, as reactivity with cyclic arginine peptide (CAP) is typically present. Antibodies targeting carbamylated proteins (anti-CarP) may occur in anti-CCP/rheumatoid factor (RF)-negative cases long before clinical onset of RA. We analysed these antibody specificities in sera from European patients with SLE in relation to phenotypes, smoking habits and imaging data. METHODS: Cases of SLE (n = 441) from Linköping, Sweden, and Leiden, the Netherlands, were classified according to American College of Rheumatology (ACR) and/or Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) criteria. IgG anti-CCP, anti-CAP and anti-CarP were analysed by immunoassays. Radiographic data from 102 Swedish patients were available. RESULTS: There were 16 Linköping (6.8%) and 11 Leiden patients (5.4%) who were anti-CCP-positive, of whom approximately one third were citrulline-dependent: 40/441 (9.1%) were anti-CarP-positive, and 33% of the anti-CarP-positive patients were identified as anti-CCP-positive. No associations were found comparing anti-CCP or anti-CarP with ACR-defined phenotypes, immunologic abnormalities or smoking habits. Radiographically confirmed erosions were found in 10 patients, and were significantly associated with anti-CCP, anti-CarP and RF. Musculoskeletal ultrasonography scores were higher in anti-CCP-positive compared to anti-CCP-negative patients. CONCLUSIONS: In the hitherto largest anti-CarP study in SLE, we demonstrate that anti-CarP is more prevalent than anti-CCP and that the overlap is limited. We obtained some evidence that both autoantibodies seem to be associated with erosivity. Similar pathogenetic mechanisms to those seen in RA may be relevant in a subgroup of SLE cases with a phenotype dominated by arthritis. Funding agencies: County Council of Ostergotland; Swedish Society for Medical Research; Swedish Rheumatism Association; Swedish Society of Medicine; Professor Nanna Svartz foundation; King Gustaf V 80-year foundation; Dutch Arthritis Foundation; IMI JU project, BeTheCure [

Cardiovascular disease has become the leading cause of mortality in patients with systemic lupus erythematosus (SLE). Accelerated atherosclerosis is considered one of the most important mechanisms implicated in the high cardiovascular (CV) mortality associated with SLE. Atherosclerosis in SLE patients arises from an interaction among classical CV risk factors, inflammatory mediators and factors specific to SLE itself. Consequently, calculating CV risk in these patients is central to decision-making on treatment to prevent CV disease. However, although Systematic COronary Risk Evaluation (SCORE) is recommended by The European League against Rheumatism (EULAR) experts and is widely used by rheumatologists for CV assessment in patients with rheumatoid arthritis and other forms of inflammatory arthritis, CV risk in SLE patients cannot be adequately evaluated with widely used charts for stratifying CV risk. Due to the lack of specific charts, assessment of traditional CV risk factors (smoking, blood pressure, diabetes, body mass index and lipid profile) and the use of validated imaging techniques to detect subclinical atherosclerosis have been proposed for the assessment of vascular disease in SLE patients. Among these techniques, calculating the intima-media thickness of the common carotid arteries measured in the far wall and the presence of plaques in the carotid system have become commonly used indicators of subclinical atherosclerosis. To a certain extent, the use of these methods allows individualized CV assessment and consequently a more useful management strategy, which can decrease CV mortality in SLE patients.

OBJECTIVE To assess drug survival and the reasons for switching anti-TNF-α therapy in SpA patients in a Spanish nationwide study. METHODS A cross-sectional study was performed. Sample size was calculated to represent all regions and hospitals throughout the country. Demographic data, patient characteristics and disease activity parameters were obtained. Drug survival and reasons for switching anti-TNF therapy were also recorded. RESULTS A total of 467 SpA patients receiving at least one anti-TNF agent were identified. Among patients who received a first, second and third anti-TNF course, 39.4%, 37.4% and 23.1% discontinued treatment, respectively. The main reasons for switching anti-TNF agents in the first course were lack or loss of efficacy (LOE) and adverse events (AEs) in 40% and 30% of switchers, respectively. Similarly, reasons for switching during the second anti-TNF course were LOE in 48% and AEs in 28% of switchers. Of the 467 SpA patients starting anti-TNF therapy, 28% switched to a second and 8% switched to a third therapy. Mean drug survival for the first, second and third anti-TNF courses were 84.4 (95% CI 78.4, 90.5), 70.2 (95% CI 61.6, 78.9) and 64.8 (95% CI 51.1, 78.5) months, respectively (P = 0.315). CONCLUSION Twenty-eight per cent of SpA patients starting anti-TNF therapy switched to a second anti-TNF agent. Drug survival did not differ among anti-TNF courses. The main reason for switching anti-TNF therapy was LOE. Switchers were more frequently women and had higher disease activity parameters at the time of the study than non-switchers.

Journal Article; Vitamin D deficiency is associated with higher cardiovascular risk and metabolic syndrome (MeS) criteria. The main objective of this study was to analyse the association of 25-hydroxyvitamin D (25-OHD) serum levels with MeS (National Cholesterol Education Program-Adult Treatment Panel-III criteria) in 46 Spanish patients with psoriasis, but without arthritis and systemic treatment, and 46 control subjects, matched by sex and age. The patients with psoriasis showed significantly lower level of 25-OHD than controls (30.5 vs. 38.3 ng/ml; p = 0.0001). Patients with MeS had significantly lower serum levels of 25-OHD than those without MeS (24.1 ± 7.5 vs. 32.8 ± 8.9, p = 0.007), and a negative correlation was found between 25-OHD and waist circumference, diastolic blood pressure, fasting glucose, and triglyceridaemia. In the control group no significant correlation between 25-OHD and MeS was found. Al-though the sample was small, our results suggest a potential protective role for 25-OHD in the metabolic profile of patients with psoriasis without arthritis. Yes

Objective To assess cardiovascular (CV) risk in psoriatic arthritis (PsA) patients without clinically evident CV disease or classic atherosclerosis risk factors according to the SCORE chart following the EULAR recommendations. Methods Eighty PsA patients without previous CV events or atherosclerosis risk factors and eighty matched controls were included. Information on demographic, anthropometric and clinical-serological data of disease was assessed. The national calibrated Systematic Coronary Risk Evaluation (SCORE) index was calculated and the association between this SCORE and clinical-serological data of these patients was analyzed. Results PsA patients had higher acute phase reactants as well as higher SCORE mean values than healthy controls (1.99 ± 3.52 vs. 1.0 ± 1.74; P = 0.028). According to SCORE definitions, 71 (89%) patients had low-intermediate CV risk and 9 (11%) were above the threshold of high risk. In the control group, 76 (95%) had low-intermediate risk and four (5%) had high CV risk. However, there were no differences in CV risk stratification between both groups ( P = 0.148). PsA patients with high-very high CV risk had longer disease duration ( P = 0.001) and higher levels of triglycerides ( P = 0.009). PsA patients showed a significant correlation between SCORE values and disease duration (β = 0.185; P = 0.0001) and the average annual levels of C reactive protein (CRPa), β = 2.38; P = 0.014. Conclusion CV risk assessment in PsA patients without clinically evident CV disease or classic atherosclerosis risk factors may be underestimated by using only the SCORE chart. In these patients, disease duration and the CRPa may help to establish a better stratification of the actual CV risk.

Background Psoriasis has been related to a higher prevalence of cardiovascular risk factors. Vitamin-D deficiency has been associated with metabolic syndrome, cardiovascular disease, and psoriasis. However, there has been no comparative study on the effects of vitamin-D status between patients with and without psoriatic arthritis. Objective The objective was to assess the relationship of 25-hydroxyvitamin D [25-(OH)D] levels with lipid and glucose metabolism parameters in psoriatic patients with and without arthritis. Methods We studied 122 patients with psoriasis (61 without arthritis and 61 with arthritis) from the psoriasis unit (dermatology department) and rheumatology department of our hospital, analyzing lipid and glucose metabolism variables and serum 25-(OH)D concentrations. Measurements were conducted within a 2-month period to minimize seasonal bias in 25-(OH)D levels. Results In the psoriatic patients without arthritis, serum 25-(OH)D levels were inversely correlated with fasting glucose ( r = −0.285; P = .026), total cholesterol ( r = −0.440; P = .000), low-density lipoprotein ( r = −0.415; P = .001), total cholesterol/high-density lipoprotein ( r = −0.303; P = .01), and triglyceride ( r = −0.280; P = .029) values. This association remained statistically significant for glucose, total cholesterol, and low-density lipoprotein after controlling for confounding factors in multivariate analysis. No association was found between serum 25-(OH)D levels and any metabolic parameter in the patients with psoriatic arthritis. Limitations This is a cross-sectional study that supports the hypothesis of an association between vitamin D and metabolic parameters but does not establish a causal relationship. Conclusions Serum 25-(OH)D was inversely related to lipid and glucose metabolism parameters in psoriatic patients without arthritis, whereas no such association was observed in psoriatic patients with arthritis. Interventional studies are warranted to assess the effects of vitamin-D supplements on the metabolic profile of psoriatic patients without arthritis.

Cellulosimicrobium cellulans has been reported as a rare cause of human pathogenesis. Infections mainly occur in immunocompromised patients and very often are associated with a foreign body. We report the first case of septic arthritis caused by C. cellulans in an immunocompetent patient. Our patient suffered a penetrating palm tree thorn injury to his left knee 8 weeks before admission. Although no foreign objects were found, they were suspected because previous reports suggest a frequent association with this microorganism, and open debridament was performed. Removal of foreign bodies related to this organism must be considered a high-priority treatment in these patients to achieve a complete recovery.

AA (secondary) amyloidosis is one of the most severe and uncommon complications of several rheumatic disorders and chronic infections such as tuberculosis (TB). Successful treatment depends on the control of the underlying inflammatory process, what can lead to an improvement or a regression in organ dysfunction. If the disorder persists, it has been reported in some cases of AA amyloidosis secondary to rheumatic diseases, that the use of biologic therapy is so far the only opportunity to reduce the development of AA amyloidosis and to reverse established deposits. We report herein a case of a latent TB infection complicated by a life-threatening AA amyloidosis presented as nephrotic syndrome. After an adequate antituberculostatic treatment, AA amyloidosis remained active and Tocilizumab (TCZ) was started with a dramatic resolution of the proteinuria, stabilization of the amyloid deposits and improvement in general condition.

Background Stratifying cardiovascular risk using risk charts is central to decision-making on treatment to prevent cardiovascular disease. EULAR task force on cardiovascular (CV) risk management in patients (pts) with inflammatory arthritis recommends the use of the SCORE chart when no local guidelines are available. In our country, two charts have been calibrated and are widely used to calculate CV mortality at 10 years, the SCORE table (cSCORE) and the Framingham-Wilson (REGICOR). Objectives To assess the CV risk in Psoriatic Arthritis (PsA) pts using the SCORE for low risk European countries (eSCORE) and compare it with the cSCORE and the REGICOR. Furthermore, we analyzed the correlation of several clinical and serological variables with these indexes and the percentage of pts that received adequate therapy for the management of CV risk. Methods This cross-sectional study included 147 consecutive pts who fulfilled the CASPAR criteria followed in our outpatient clinics. Patients with a previous CV event and diabetics were excluded. The following data were recorded for analysis: sex, age, body mass index, classic CV risk factors, lipid profile, duration in years since diagnosis, clinical patterns of the PsA, treatment, and inflammatory markers. The eSCORE function model, the cSCORE and the REGICOR were compared and the concordance (Kappa Index) between the three guides calculated. According to our national guidelines, a high CV risk has been defined by a SCORE ≥5% and REGICOR ≥10%, the cutoff point recommended to start treatment. Results The mean eSCORE was 1,36±2,25% and 18 pts (11,4%) were above the threshold of high or very high CV risk (≥5%). After applying the cSCORE the values were 2,23±3,48% and with REGICOR were 4±3,4%. Therefore, 34 pts (21,5%) and 20 pts (12,7%) were reclassified as high o very high CV risk (SCORE ≥5%, REGICOR ≥10%) respectively. Multivariate regression analysis showed that the most important prognostic factor for predicting the cSCORE was the age (Total R-square 64%; p=0,000) followed by systolic blood pressure. Of notice, the ESR was also a prognostic factor of the SCORE (p Conclusions Assessment of the CV risk in PsA pts applying the eSCORE or REGICOR leads to an underestimation of the risk in comparison with the application of the cSCORE, which have an impact on the correct management of these pts. Variable analysis showed that ESR, but not CRP, was a prognostic factor of the SCORE what suggests that sustained inflammation could play a role in the increase of CV risk. References Peters MJL et al. EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis. Ann Rheum Dis. 2010;69:325–331. Disclosure of Interest None Declared

Background EULAR task force recommendations in the cardiovascular (CV) risk were published in 2010. EULAR recommends the use of the SCORE when no local guidelines are available. In our country, two charts have been calibrated and are widely used to calculate cardiovascular mortality at 10 years, the SCORE table, calibrated by the National Cardiology Society (cSCORE) and the Framingham-Wilson score (REGICOR). Objectives To assess the CV risk in Ankylosing Spondilytis (AS) patients (pts) using the SCORE for low risk European countries (eSCORE) and compare it with the cSCORE and the REGICOR. Furthermore, we analyzed the correlation of several clinical and serological variables with these indexes, and the percentage of high and very high CV risk pts receiving an adequate therapy for its management, coxibs and/or NSAIDs. Methods This cross-sectional study included 103 consecutive pts who fulfilled the modified New York criteria for AS followed in our outpatient clinics. Patients with a previous CV event and diabetics were excluded. The following data were recorded for logistic regression analysis: sex, age, body mass index, classic CV risk factors, lipid profile, duration in months since diagnosis, clinical patterns of the AS, treatment, and inflammatory markers (p Results Based on the classic CV risk factors, the eSCORE was 1,78±2,55% (mean ± standard deviation) and 11 pts (10,67%) were above the threshold of high or very high CV risk (≥5%). After applying the cSCORE the values were 2,87±3,78% and with REGICOR were 4,72±4,36%. Therefore, 24 pts (23,3%) and 12 pts (11,65%) were reclassified above the threshold respectively. Multivariate regression analysis showed that the most important prognostic factor for predicting the cSCORE was the duration in months since diagnosis (p Conclusions Assessment of the CV risk in AS pts applying the eSCORE and REGICOR leads to an underestimation of the CV risk, which have an impact on the correct management of these pts. Duration in months since diagnosis and ESR were prognostic factors of the cSCORE, what suggests that sustained inflammation could play a role in the increase of CV risk. Although EULAR recommends caution about prescribing coxibs and NSAIDs in high and very high risk pts, a high percentage of pts received these therapies. References Peters MJL et al. EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis. Ann Rheum Dis. 2010;69:325–331 Disclosure of Interest None Declared

Background Patients with psoriatic arthritis (PsA) and cutaneous psoriasis alone (PsC) are known to have an increased risk of Cardiovascular (CV) disease. The increase of Carotid Intima-Media Thickness (cIMT) in patients with PsA and PsC has been demonstrated in several studies and serve as surrogate measure for cardiovascular diseases. However, there are no studies so far comparing the extent of subclinical atherosclerosis among them and with controls. Objectives Our aim was to compare the prevalence of subclinical atherosclerosis, as measured by cIMT, between patients with PsA, PsC alone and controls. Methods This cross-sectional study included 77 consecutive PsA patients who fulfilled the CASPAR criteria, compared to 77 patients with PsC and 77 age and sex matched controls. Patients with a previous CV event and diabetics were excluded. Inflammatory arthritis in PS patients was excluded by a rheumatologist in our outpatient clinic. Measurement of cIMT was performed using the Esaote MyLab25Gold Cardiovascular ultrasound machine and an automated edge detection software (QIMT). Presence of atherosclerotic plaques and the highest value of cIMT were recorded. A one way ANOVA was performed to analyze the statistical difference of cIMT between groups. Furthermore, multivariate regression analysis was used to adjust for the following variables: sex, age, body mass index, classic CV risk factors, lipid profile, duration in months since diagnosis of PsA and PsC, clinical patterns of the PsA and PsC, treatment, activity of the disease, and inflammatory markers (p Results The mean age of all the patients was 47,27±11,39 (mean ± standard deviation) and48,1% were females. The mean of the cIMT in the group of PsA was 659±118 microns and 8 pts (10,4%) presented atheroscletoric plaques. The mean for the cIMT calculated in PS patients was 648±102 microns, and plaques were present in 9 patients (11,7%). In the group of healthy controls, the mean was 614±96 microns, and plaques were seen in 2 patients (%). Statistical difference of cIMT intergroup was significant (p=0,02). Multivariate regression analysis showed that the most important prognostic factors for predicting the cIMT in the PsA pts were the age and the CRP (p Conclusions cIMT and prevalence of atherosclerotic plaques are increased in pts with PsA and PsC compared with healthy controls.Although pts with PsA presented a greater cIMT than matched pts with PsC the prevalence of plaques was similar in both groups. References Gonzalez-Juanatey C et al. High prevalence of subclinical atherosclerosis in psoriatic arthritis patients without clinically evident cardiovascular disease or classic atherosclerosis risk factors. Arthritis Rheum. 2007;57:1074-80. Disclosure of Interest None Declared

Background Patients with psoriatic arthritis (PsA) and with moderate to severe chronic plaque psoriasis (PS) have a higher prevalence of cardiovascular (CV) risk factors and atherosclerosis. The Ankle-Brachial pressure Index (ABPI) at rest, a non-invasive and inexpensive tool for the assessment of CV risk, is the ratio of the ankle and the brachial systolic blood pressure. This indexcan be used to identify individuals who are at high CV risk. An ankle-brachial index Objectives Our aim was to determine the prevalence of an abnormal ABPI in patients with psoriatic arthritis (PsA), cutaneous psoriasis alone (PS) and healthy controls and to correlate with clinical and serological parameters. Methods This cross-sectional study included 86 consecutive patients who fulfilled the Classification Criteria for Psoriatic Arthritis (CASPAR criteria), compared to 86 patients with cutaneous PS alone and 86 age and sex matched controls. Patients with a previous CV event and diabetics were excluded. Inflammatory arthritis in PS patients was excluded by a rheumatologist in our outpatient clinic. The ABPI was measured using a Mini Dopplex with 8 MHz Vascular Probe in the arms and legs. A ratio of Results The mean age of all the patients was 47,87±11,52 (mean ± standard deviation). The ABPI in the group of PsA patients was 0,93±0,09, and 20 patients (23,25%), had an abnormal index ( Conclusions There is an increased prevalence of an abnormal ABPI in patients with PsA and PS comparing with controls implying an increased risk of cardiovascular disease. The ABPI may be a simple non-invasive tool for the early detection of accelerated atheroma in these patients. References Alkaabi JK et al. Rheumatoid arthritis and macrovascular disease. Rheumatology (Oxford). 2003;42:292–297. Disclosure of Interest None Declared

Supporting information:S1 Text. Information on selected previous studies and compatibility with the current study. It includes two tables. Table A: List of SNPs selected for this study with references and the corresponding quality control results in the current study. Table B: Characteristics of the patients included in previous studies compared with the current study. https://doi.org/10.1371/journal.pone.0196793.s001 (DOCX) S1 Dataset. Raw data with all the variables and patients considered in this study. https://doi.org/10.1371/journal.pone.0196793.s002 (XLSX), Genetic biomarkers are sought to personalize treatment of patients with rheumatoid arthritis (RA), given their variable response to TNF inhibitors (TNFi). However, no genetic biomaker is yet sufficiently validated. Here, we report a validation study of 18 previously reported genetic biomarkers, including 11 from GWAS of response to TNFi. The validation was attempted in 581 patients with RA that had not been treated with biologic antirheumatic drugs previously. Their response to TNFi was evaluated at 3, 6 and 12 months in two ways: change in the DAS28 measure of disease activity, and according to the EULAR criteria for response to antirheumatic drugs. Association of these parameters with the genotypes, obtained by PCR amplification followed by single-base extension, was tested with regression analysis. These analyses were adjusted for baseline DAS28, sex, and the specific TNFi. However, none of the proposed biomarkers was validated, as none showed association with response to TNFi in our study, even at the time of assessment and with the outcome that showed the most significant result in previous studies. These negative results are notable because this was the first independent validation study for 12 of the biomarkers, and because they indicate that prudence is needed in the interpretation of the proposed biomarkers of response to TNFi even when they are supported by very low p values. The results also emphasize the requirement of independent replication for validation, and the need to search protocols that could increase reproducibility of the biomarkers of response to TNFi., Funding: This work was supported by the Instituto de Salud Carlos III (Spain) through grants [PI14/01651 and RD16/0012/0014 to AG; and PI12/01909 to JJG-R]. These grants are partially financed by the European Regional Development Fund of the EU (FEDER). R. L.-R. was supported by Instituto de Salud Carlos III (Spain) through a Postdoctoral Contract “Sara Borrell” [CD14/00186]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.