Search

Objective We aimed to characterize the clinical phenotype of patients with SSc based on autoantibodies (topoisomerase antibody (Scl-70), ACA and ANA). Methods We included patients with SSc who fulfilled the 2013 ACR/EULAR criteria, with disease duration ≤15 years. Six groups of patients were defined: ACA-lcSSC, Scl-70-lcSSc, ANA-lcSSc, Scl-70-dcSSc, ANA-dcSSc and ACA-dcSSc patients. We compared the different groups of patients. In the ANA subgroup, we included patients negative for SSc-specific antibodies (Scl-70 and ACA). We assessed the following: risk of interstitial lung disease (ILD), myositis, scleroderma renal crisis, cardiac involvement, gastrointestinal involvement, pulmonary hypertension, treatment, cancer and all-cause mortality. Results One hundred and thirteen SSc patients were included: 72 (64%) females, 82 (73%) lcSSc and 31 (27%) dcSSc. Among patients with lcSSc, 43 (52%) were ACA+, 16 (19%) Scl-70+ and 23 (28%) ANA+, and among patients with dcSSc, 13 (42%) patients were Scl-70+, 11 (35%) ANA+ and 7 (23%) ACA+. Scl-70-lcSSc patients had a significantly shorter time from RP to SSc diagnosis (P = 0.04), higher CRP (P = 0.04), renal scleroderma crisis (P = 0.02), ILD (P = 0.03) and diastolic dysfunction (P = 0.04) than ANA-lcSSc patients. Scl-70-dcSSc patients had a higher rate of myositis (P = 0.04), renal crisis (P = 0.03), CRP elevation (P = 0.002), ILD (P = 0.04), pericardial effusion (P = 0.03) and cancer (P = 0.04) than ANA-dcSSc patients. The risk of ILD was higher in Scl-70 patients during the first 10 years than in ACA+ and ANA+ patients (P = 0.03 and P = 0.02, respectively). The risk of major organ involvement was higher in Scl-70+ patients, followed by ANA+ and ACA+ patients, throughout 15 years of follow-up. All-cause mortality was higher in dcSSc patients than in lcSSc patients, but no differences were found regarding antibody positivity. Conclusion We have characterized the clinical phenotype of patients based on autoantibodies: Scl-70 patients show the greatest risk of major organ involvement, followed by ANA+ patients and ACA+ patients. The risk of ILD in Scl-70+ patients suggests that these patients should be monitored closely, irrespective of skin involvement. These results might provide new ways to help with the early diagnosis and management and in assessment of the prognosis of the disease.

Pregnancies in Systemic lupus erythematosus (SLE) are considered high risk and associated with maternal and obstetric complications.To determine the most important predictors for each of the main adverse pregnancy outcomes in SLE patients.Patients with SLE were retrospectively analysed from 1990 to 2020. Maternal and fetal complications in pregnant women with SLE were retrieved. We compared clinical and analytical characteristics of SLE patients with adverse pregnancy outcomes to controls with SLE diagnosis without adverse pregnancy outcomes. Qualitative data were analysed by Chi-square test and Fisher's exact test. Continuous variables were analysed by using Student's t test. Multiple logistic regression was performed to determine the predictive factors for adverse pregnancy outcomes with adjustment of confounding factors.135 multiparous women were included (42% with adverse pregnancy outcomes). A total of 57 pregnancies (42%) were linked to adverse outcomes. The occurrence of abortion was correlated with anti-DNAds (β = 0.71, p = 0.04), renal involvement (β = 0.28, p 0.03), antiphospholipid antibodies (APA) (β = 0.29, p 0.03), erythrocyte sedimentation rate (ESR) elevation (β = 0.81, p = 0.02) and C-reactive protein (CPR) elevation (β = 0.91, p = 0.01). Stillbirth was also correlated with renal involvement (β = 0.26, p = 0.04), APA (β = 0.22, p = 0.03) and ESR elevation (β = 0.53, p = 0.02). Preeclampsia was correlated with direct Coombs positivity (β = 0.42, p = 0.01), serositis (β = 0.31, p = 0.02), ESR elevation (β = 0.52, p = 0.03) and CPR elevation (β = 0.32, p = 0.04). Neonatal Lupus was correlated with anti-RNP (β = 0.16, p = 0.03) and anti-Ro/SSA (β = 0.16, p 0.02).The most unfavourable pregnancy outcome in women with SLE was spontaneous abortion. Renal involvement, anti-DNAds positivity, antiphospholipid antibody positivity, anti-Ro/SSA, elevated ESR and a younger age at disease onset increased the risk of pregnancy complications.

Background/Aims Uveitis is the most frequent extra-articular manifestation of spondylarthritis (SpA), characterised by a sudden onset, often unilateral, anterior and recurrent, and may be the first clinical manifestation of the disease. The lack of standardised and validated outcome measures in uveitis makes it difficult to evaluate the efficacy of and refractoriness to treatment and determine factors associated with adverse outcomes. The objective of our study was to develop a prognostic outcome score for patients with uveitis associated with spondylarthritis (SpA-U) and determine factors associated with adverse outcomes in uveitis associated with SpA-U in patients under systemic treatment. Methods The outcome score was defined by best-corrected visual acuity (BCVA), anterior chamber inflammation, macular edema and inflammation of posterior chamber, global assessment, and refractoriness to treatment. Factors associated with adverse outcomes in uveitis were studied using linear regression. For categorical factors, marginal averages and their standard errors are displayed together with linear regression coefficients with 95% confidence intervals (CI). For continuous factors, averages and standard deviations are reported in addition to linear regression coefficients with 95% CI. Two regression coefficients are reported for each variable: unadjusted and adjusted for age at diagnosis and sex. Results 250 uveitis outbreaks were included. 62 uveitis outbreaks (31%) were classified as severe, 42 as moderate (21%), and 93 as mild (47%) based on the definition and construction of outcome score. The results of the linear regression model revealed that the uveitis activity was more severe in patients with smoking history (β = 0.34), axial and peripheral involvement (β = 0.43), a BASDAI>4 (β = 0.32), positive HLA-B27 (β = 0.29), female sex (β = 0.19), patients with CRP elevation (β = 0.002) and bilateral ocular involvement (β = 0.32). At the same time, shorter disease evolution (β=-0.02) was associated with less severe uveitis activity. Conclusion We have determined factors associated with adverse outcomes in SpA-U by developing an outcome score that integrates ocular inflammatory activity, visual acuity, global assessment, and refractoriness to treatment. Disclosure C. Sieiro Santos: None. I. Sendino Tenorio: None. C. Álvarez Castro: None. E. Díez Álvarez: None.

Background/Aims Interstitial lung disease (ILD) and pulmonary hypertension are the leading cause of death in patients with systemic sclerosis (SSc). Identifying SSc-ILD development and initiating treatment is essential to optimize therapeutic benefit. We aimed to identify predictors of SSc-ILD and compared early (5 years from diagnosis) onset. Methods We conducted a retrospective cohort study by including patients diagnosed with SSc from 1980 to 2020 followed in our unit and compared the clinical profile of patients with SSc-ILD to control SSc-non-ILD patients. Demographic features, clinical and immunological characteristics and baseline pulmonary function were retrieved. Logistic regression modelling was run to identify factors associated with SSc-ILD development. Factors associated with ILD were determined as factors associated with early or late onset. Bonferroni correction was used to limit Type I errors. Results We have included 103 patients from our patient registry from 1980 to 2021 (42% with SSc-ILD). Logistic regression identified risk factors associated with increased or decreased odds ratio for developing ILD is summarized in table 1: smoking history, male sex, the presence of myositis, anti-Scl70 and anti-Ro52 positivity, baseline pulmonary function including FVC and DLCO, mMRC (modified medical research council) dyspnea scale>2, mMSS (modified rodnan skin score)>3 and late pattern in capillaroscopy. Older age at SSc diagnosis, the presence of telangiectasias and smoking status was associated with increased odds of SSc-ILD onset before 5 years, while male gender, the presence of myositis and antiphospholid antibodies were associated with late-onset SSc-ILD. Conclusion We identified 11 factors significantly associated with risk of developing SSc-ILD. We identified early and late-onset predictors for ILD-SSc. Disclosure C. Sieiro Santos: None. R. Rego Salgueiro: None. C. Moriano Morales: None. C. Álvarez Castro: None. E. Díez Álvarez: None.

Background/Aims Patients with immune-mediated rheumatic diseases (IMRD) are commonly treated with immunosuppressors and are prone to infections. Recently introduced mRNA SARS-Cov2 vaccines have demonstrated extraordinary efficacy across all ages. Immunosuppressed patients were excluded from phase III trials with SARS-We aim to fully characterize B and T cell immune responses elicited by mRNA SARS-Cov2 vaccines in patients with rheumatic diseases under immunotherapies, and to identify which drugs reduce vaccinés immunogenicity. Methods Humoral, CD4 and CD8 immune responses were investigated in 147 SARS-Cov2-naïve patients with selected rheumatic diseases under immunosuppression after a two-dose regimen of SARS-Cov2 mRNA vaccine. Responses were compared with age, gender, and disease-matched IMRD patients not receiving immunosuppressors and with healthy controls Results IMRD patients showed decreased seroconversion rates (63% vs 100%, p = 0.04) and cellular immune responses (59% vs 100%, p = 0.007). Patients on methotrexate achieved seroconversion in 62% of cases and cellular responses in 80% of cases. Abatacept deeply affected humoral and cellular responses. Rituximab (31% responders) and belimumab (50% responders) showed severely impaired humoral responses but cellular responses were often preserved. Antibody titers were reduced with mycophenolate and azathioprine but preserved with leflunomide. Conclusion IMRD patients exhibit impaired SARS-CoV-2 vaccine-immunogenicity, variably reduced with immunosuppressors. Among commonly used therapies, abatacept and B-cell depleting therapies show the most deleterious effects, while anticytokines preserved immunogenicity. The effects of cumulative methotrexate and glucocorticoid doses on immunogenicity should be considered. Humoral and cellular responses are weakly correlated, but CD4 and CD8 tightly correlate. Seroconversion alone might not reflect the vaccine’s immunogenicity. Disclosure C. Sieiro Santos: None. S. Calleja Antolín: None. C. Moriano Morales: None. C. Álvarez Castro: None. E. Díez Álvarez: None. J. Garcia Ruiz de Morales: None.

Objective To investigate the human leukocyte antigen (HLA) association with anti-synthetase syndrome (ASSD). Methods We conducted the largest immunogenetic HLA-DRB1 and HLA-B study to date in a homogeneous cohort of 168 Caucasian patients with ASSD and 486 ethnically matched healthy controls by sequencing-based-typing. Results A statistically significant increase of HLA-DRB1*03:01 and HLA-B*08:01 alleles in patients with ASSD compared to healthy controls was disclosed (26.2% versus 12.2%, P = 1.56E–09, odds ratio–OR [95% confidence interval–CI] = 2.54 [1.84–3.50] and 21.4% versus 5.5%, P = 18.95E–18, OR [95% CI] = 4.73 [3.18–7.05]; respectively). Additionally, HLA-DRB1*07:01 allele was significantly decreased in patients with ASSD compared to controls (9.2% versus 17.5%, P = 0.0003, OR [95% CI] = 0.48 [0.31–0.72]). Moreover, a statistically significant increase of HLA-DRB1*03:01 allele in anti-Jo-1 positive compared to anti-Jo-1 negative patients with ASSD was observed (31.8% versus 15.5%, P = 0.001, OR [95% CI] = 2.54 [1.39–4.81]). Similar findings were observed when HLA carrier frequencies were assessed. The HLA-DRB1*03:01 association with anti-Jo-1 was unrelated to smoking history. No HLA differences in patients with ASSD stratified according to the presence/absence of the most representative non-anti-Jo-1 anti-synthetase autoantibodies (anti-PL-12 and anti-PL-7), arthritis, myositis or interstitial lung disease were observed. Conclusions Our results support the association of the HLA complex with the susceptibility to ASSD.

Background Oral and/or genital aphthous ulcers are the most common symptoms of Behçet´s disease (BD), and are often refractory to conventional treatment. The inhibitor of phosphodiesterase-4 apremilast (APR) has demonstrated efficacy in the treatment of this manifestations. The objective of the present study was to assess the efficacy of APR in the management of refractory oral and/or genital ulcers in patients with BD. Methods National multicenter open-label observational study on BD patients with recurrent oral and/or genital ulcers. In all cases orogenital ulcers were refractory to conventional therapy. APR was given and maintained at standard dose of 30 mg twice daily. The main outcome was the achievement of oral and/or genital ulcers remission. Efficacy of APR for other clinical manifestations was also evaluated. Results We included 51 patients (35 women/16 men; mean age 44.7 ± 13.2 years). Before APR, all patients had received several systemic conventional and/or biologic drugs. APR was initiated because of refractory oral (n = 19) or genital (n = 2) aphthous ulcers or both (n = 30). Other manifestations found at APR onset were arthralgia/arthritis (n = 16), folliculitis/pseudofolliculitis (n = 14), erythema nodosum (n = 3), furunculosis (n = 2), paradoxical psoriasis induced by TNFα-inhibitors (n = 2), ileitis (n = 2), deep venous thrombosis (n = 2), leg ulcers (n = 1), erythematosus and scaly skin lesions (n = 1), fever (n = 1), unilateral anterior uveitis (n = 1) and neurobehçet (n = 1). After a mean follow-up of 8.5 ± 6.9 months, most patients had experienced improvement of orogenital ulcers and prednisone dose had been successfully reduced or discontinued. APR also yielded improvement of some non-aphthous manifestations such as the cutaneous follicular and intestinal manifestations. However, the effect on musculoskeletal manifestations was variable. Conclusion APR yielded a rapid and maintained improvement of refractory mucocutaneous ulcers of BD, even in patients refractory to several systemic drugs including biologic therapy.

Aquest projecte té com a objectiu dissenyar un sistema que permeti la millora en la neteja dels models actualment implementats de maquinària de producció de pa, a l’empresa on s’han realitzat les pràctiques, Tecnotrade Bakery System Lines Group SI. Al llarg d’aquest projecte, s’analitzaran les diferents solucions tant a nivell de mobilitat, de resistència i de viabilitat de econòmica. Alguns components per realitzar la solució han estat dissenyats, i d’altres han estat extrets de proveïdors. En tots els casos, s’ha treballat amb el programari Inventor, el qual permet tant el disseny, com la realització de simulacions per analitzar les tensions i desplaçaments patits pels components. S’ha realitzat un estudi dels costos que comporten portar a terme aquesta millora. A través de simulacions, s’ha comprovat la funcionalitat a l’hora d’implementar la solució en el model actual. Aquesta solució s’ha realitzat buscant el menor cost possible de la millora. S’ha comprovat que la solució no requereix d’elements mòbils complexos, fent així, que es redueixin els costos. També s’ha pogut comprovar com els desplaçaments teòrics han estat de l’ordre de 0,03 mm, mostrant així la viabilitat de la solució. La solució plantejada compta de la implementació d’unes comportes al mòdul de l’alimentador, juntament amb dues tanques tant d’obertura horitzontal, com d’obertura vertical, les quals garanteixen l’estanqueïtat a l’interior de l’alimentador. També compta amb la implementació de frontisses convencionals que permeten l’obertura de les comportes.

Background Remission and Low Disease activity state (LDAS) are physician assessed treat to target-T2T outcomes for Systemic Lupus Erythematosus (SLE). Lupus Impact Tracker (LIT), a ten-item unidimensional patient reported tool has good psychometric properties and responds to patient reported changes in health, physician based disease activity (DA) and composite response Index (SRI). Herein we report responsiveness of LIT to changes in physician (T2T) and patient assessed outcomes (DA by SLAQ and health status (EQ5D)) among SLE patients from the largest European SLE registry- cohort. Methods One-year longitudinal, observational, multi-center data from 1364 adult patients with SLE meeting 1997 ACR criteria were obtained from baseline and year 1 visit. This included demographics, patient reported tools (LIT, EQ5D VAS, SLAQ), SLE (activity-SLEDAI) and medications. Remission off therapy (ROFT) was defined as SLEDAI=0 without prednisone or Immunosuppressive/s. Remission on-therapy (RONT) was SLEDAI=0 and a prednisone dose 5 mg/day and/or Immunosuppressive/s (maintenance dose). LDAS (modified) was defined as SLEDAI 4, prednisone dose 9 mg/day and/or maintenance immunosuppressive/s. Non-optimal (NO) disease status was SLEDAI >4 and/or prednisone dose >9 mg/day and/or immunosuppressive/s in induction dose. Use of hydroxychloroquine was permitted in all groups. LIT values were compared using mixed models. Responsiveness was evaluated by standard response means (SRM) in groups with changes in DA (T2T, SLAQ) and EQ5D VAS as anchors. We did not have enough observations for stratified analysis for SLE patients with fibromyalgia. Results 1232/1364 (90%) were women, and 95% were Caucasian. Mean (SD) SLEDAI and SDI were 2.6 (3.5) and 0.7 (1.1) respectively. As (i) DA was low (median 2) in LDAS, (ii) steroid use was more prevalent in RONT than LDAS, we combined RONT and LDAS into one category to analyse patient relevant differences in LIT. LIT was responsiveness in the appropriate direction with improvement and worsening in disease activity (T2T and SLAQ) and health status (EQ5D VAS) over time. Mean LIT changes to and from NO to RONT/LDAS ranged from 3–5 (table 1), while it declined by over 8.5 with change from NO to ROFT. We had limited observations for ROFT to NO change. Mean change in LIT ranged from −3 to 3 with improvement and worsening in SLAQ, and from −7.6 to 6 with improvement and worsening in EQ5D VAS. Conclusions LIT responds appropriately in both directions to changes in physician (T2T) as well as patient relevant (DA and health status) outcomes among Spanish SLE patients. Funding Source(s): None

Objective: To compare the prevalence of the main comorbidities in two large cohorts of patients with Primary Sjogren's Syndrome (pSS) and Systemic Lupus Erythematosus (SLE), with focus on cardiovascular (CV) diseases. Methods: Cross-sectional multicenter study where the prevalence of more relevant comorbidities in two cohorts was compared. Patients under follow-up from the SJOGRENSER (Spanish Rheumatology Society Register of pSS) and RELESSER (Spanish Rheumatology Society Register of SLE) registries, and who fulfilled the 2002-AECG and 1997-ACR classification criteria, respectively, were included. A binomial logistic regression analysis was carried out to explore potential differences, making general adjustments for age, sex and disease duration and specific adjustments for each variable, including CV risk factors and treatments, when it was judged appropriate. Results: A total of 437 pSS patients (95% female) and 2,926 SLE patients (89% female) were included. Mean age: 58.6 (p55-p75: 50.0-69.9) and 45.1 years (36.4-56.3), respectively (p

Objectives To investigate the primary respiratory manifestations (PRM) in SLE. Methods All patients in the RELESSER cohort were retrospectively investigated for the presence of PRM Results At least one PRM was present in 11.3% (365/3215) of cases. The most common was pleurisy, occurring in 21.1% of patients, followed by ALP in 3.6%, PE in 2.9%, PPH 4%, DILD in 2%, DAH in 0.8%, and SLS in 0.8%. The variables associated with the presence of PPM are shown in the following table 1: Conclusions PPM independently contributed to a decreased survival in SLE Disclosure of Interest None declared

Background: Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease with a complex genetic inheritance. Genome-wide association studies (GWAS) have significantly increased the number of significant loci associated with SLE risk. To date, however, established loci account for less than 30% of the disease heritability and additional risk variants have yet to be identified. Here we performed a GWAS followed by a meta-analysis to identify new genome-wide significant loci for SLE. Methods: We genotyped a cohort of 907 patients with SLE (cases) and 1524 healthy controls from Spain and performed imputation using the 1000 Genomes reference data. We tested for association using logistic regression with correction for the principal components of variation. Meta-analysis of the association results was subsequently performed on 7,110,321 variants using genetic data from a large cohort of 4036 patients with SLE and 6959 controls of Northern European ancestry. Genetic association was also tested at the pathway level after removing the effect of known risk loci using PASCAL software. Results: We identified five new loci associated with SLE at the genome-wide level of significance (p < 5 × 10? 8): GRB2, SMYD3, ST8SIA4, LAT2 and ARHGAP27. Pathway analysis revealed several biological processes significantly associated with SLE risk: B cell receptor signaling (p = 5.28 × 10? 6), CTLA4 co-stimulation during T cell activation (p = 3.06 × 10? 5), interleukin-4 signaling (p = 3.97 × 10? 5) and cell surface interactions at the vascular wall (p = 4.63 × 10? 5). Conclusions: Our results identify five novel loci for SLE susceptibility, and biologic pathways associated via multiple low-effect-size loci. This study was funded by the Spanish Ministry of Economy and Competitiveness (grant numbers: PSE-010000-2006-6 and IPT-010000-2010-36). This work has been also sponsored by the grant SEV-2011-00067 of Severo Ochoa Program, awarded by the Spanish Government. This work was supported by an EFSD/Lilly research fellowship. Josep M. Mercader was supported by Sara Borrell Fellowship from the Instituto Carlos III. Sílvia Bonàs was awarded an FI-DGR Fellowship from FI-DGR 2013 from Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR, Generalitat de Catalunya). The study sponsors had no role in the design of the study, collection, analysis or interpretation of the data.

Background: Systemic lupus erythematosus (SLE) is a genetically complex rheumatic disease characterized by heterogeneous clinical manifestations of unknown etiology. Recent studies have suggested the existence of a genetic basis for SLE heterogeneity. The objective of the present study was to identify new genetic variation associated with the clinically relevant phenotypes in SLE. Methods: A two-stage pathway-based approach was used to identify the genetic variation associated with the main clinical phenotypes in SLE. In the discovery stage, 482 SLE patients were genotyped using Illumina Human Quad610 microarrays. Association between 798 reference genetic pathways from the Molecular Signatures Database and 11 SLE phenotypes was tested using the set-based method implemented in PLINK software. Pathways significantly associated after multiple test correction were subsequently tested for replication in an independent cohort of 425 SLE patients. Using an in silico approach, we analyzed the functional effects of common SLE therapies on the replicated genetic pathways. The association of known SLE risk variants with the development of the clinical phenotypes was also analyzed. Results: In the discovery stage, we found a significant association between the vascular endothelial growth factor (VEGF) pathway and oral ulceration (P value for false discovery rate (P FDR ) < 0.05), and between the negative regulation signaling pathway of retinoic acid inducible gene-I/melanoma differentiation associated gene 5 and the production of antinuclear antibodies (P FDR < 0.05). In the replication stage, we validated the association between the VEGF pathway and oral ulceration. Therapies commonly used to treat mucocutaneous phenotypes in SLE were found to strongly influence VEGF pathway gene expression (P = 4.60e-4 to 5.38e-14). Analysis of known SLE risk loci identified a strong association between PTPN22 and the risk of hematologic disorder and with the development of antinuclear antibodies. Conclusions: The present study has identified VEGF genetic pathway association with the risk of oral ulceration in SLE. New therapies targeting the VEGF pathway could be more effective in reducing the severity of this phenotype. These findings represent a first step towards the understanding of the genetic basis of phenotype heterogeneity in SLE, This study was funded by the Spanish Ministry of Economy and Competitiveness (grant numbers: PSE-010000-2006-6 and IPT-010000-2010-36 and by the “Agència de Gestió d’Ajuts Universitaris i de Recerca” (AGAUR, Generalitat de Catalunya, FI-DGR 2016, grant number: 00587)

We aimed to describe juvenile-onset systemic lupus erythematosus (jSLE) features and to establish its differences compared to adult-onset SLE (aSLE) from a large national database.Data from patients (≥4 ACR criteria) included in Spanish Society of Rheumatology Lupus Registry (RELESSER) were analysed. Sociodemographic, clinical, serological, activity, treatment, cumulative damage, comorbidities and severity data were collected. Patients with disease onset18 years were described and compared to those with disease onset ≥18 years.We reviewed 3,428 aSLE patients (89.6% women) and 484 jSLE patients (89.8% girls), 93% Caucasian (both groups). Mean age at diagnosis was 38.1±14 and 16.6±6.3 years (p0.001) and mean age at the end of follow-up was 48.8±14.3 and 31.5±30 years (p0.001), respectively. jSLE showed significantly more clinical (including lymphadenopathy, fever, malar rash, mucosal ulcers, pericarditis, pleuritis, Raynaud's phenomenon, lupus nephritis, recurrent nephritis, histologic nephritis changes, thrombocytopenia, haemolytic anaemia, thrombotic thrombocytopenic purpura, seizures, lupus headache and organic brain syndrome) and immunological (a-dsDNA and a-Sm antibodies, hypocomplementaemia) involvement than did aSLE, except for secondary Sjögren's syndrome, a-Ro antibodies, fibromyalgia and osteoporosis. jSLE also showed more SLE family history, longer diagnosis delay, higher SLEDAI and Katz scores, but lower Charlson scores than aSLE. Several specific domains were more frequently involved in SLICC/ACR DI in jSLE. jSLE patients more frequently underwent all SLE-related treatment and procedures, as well as dialysis and kidney transplantations.jSLE shares many clinical and serological features with aSLE. However, jSLE patients typically manifested more activity, severity, cumulative damage in certain areas, than their aSLE counterparts.

To compare the prevalence of the main comorbidities in 2 large cohorts of patients with primary Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE), with a focus on cardiovascular (CV) diseases.This was a cross-sectional multicenter study where the prevalence of more relevant comorbidities in 2 cohorts was compared. Patients under followup from SJOGRENSER (Spanish Rheumatology Society Registry of Primary SS) and RELESSER (Spanish Rheumatology Society Registry of SLE), and who fulfilled the 2002 American-European Consensus Group and 1997 American College of Rheumatology classification criteria, respectively, were included. A binomial logistic regression analysis was carried out to explore potential differences, making general adjustments for age, sex, and disease duration and specific adjustments for each variable, including CV risk factors and treatments, when appropriate.A total of 437 primary SS patients (95% female) and 2,926 SLE patients (89% female) were included. The mean age was 58.6 years (interquartile range [IQR] 50.0-69.9 years) for primary SS patients and 45.1 years (IQR 36.4-56.3 years) for SLE patients (P 0.001), and disease duration was 10.4 years (IQR 6.0-16.7 years) and 13.0 years (IQR 7.45-19.76 years), respectively (P 0.001). Smoking, dyslipidemia, and arterial hypertension were associated less frequently with primary SS (odds ratio [OR] 0.36 [95% confidence interval (95% CI) 0.28-0.48], 0.74 [95% CI 0.58-0.94], and 0.50 [95% CI 0.38-0.66], respectively) as were life-threatening CV events (i.e., stroke or myocardial infarction; OR 0.57 [95% CI 0.35-0.92]). Conversely, lymphoma was associated more frequently with primary SS (OR 4.41 [95% CI 1.35-14.43]). The prevalence of severe infection was lower in primary SS than in SLE (10.1% versus 16.9%; OR 0.54 [95% CI 0.39-0.76]; P 0.001).Primary SS patients have a consistently less serious CV comorbidity burden and a lower prevalence of severe infection than those with SLE. In contrast, their risk of lymphoma is greater.

Objectives. To identify patterns (clusters) of damage manifestations within a large cohort of SLE patients and evaluate the potential association of these clusters with a higher risk of mortality. Methods. This is a multicentre, descriptive, cross-sectional study of a cohort of 3656 SLE patients from the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics Damage Index. Using cluster analysis, groups of patients with similar patterns of damage manifestations were identified. Then, overall clusters were compared as well as the subgroup of patients within every cluster with disease duration shorter than 5 years. Results. Three damage clusters were identified. Cluster (80.6% of patients) presented a lower amount of individuals with damage (23.2 vs 10096 in clusters 2 and 3. P < 0.001). Cluster 2 (11.4% of patients) was characterized by musculoskeletal damage in all patients. Cluster 3 0.096 of patients) was the only group with cardiovascular damage, and this was present in all patients. The overall mortality rate of patients in clusters 2 and 3 was higher than that in cluster 1 (P < 0.001 for both comparisons) and in patients with disease duration shorter than 5 years as well. Conclusion. In a large cohort of SLE patients, cardiovascular and musculoskeletal damage manifestations were the two dominant forms of damage to sort patients into clinically meaningful clusters. Both in early and late stages of the disease, there was a significant association of these clusters with an increased risk of mortality. Physicians should pay special attention to the early prevention of damage in these two systems.

OBJECTIVES: To estimate the incidence of severe infection and investigate the associated factors and clinical impact in a large systemic lupus erythematosus (SLE) retrospective cohort. METHODS: All patients in the Spanish Rheumatology Society Lupus Registry (RELESSER) who meet ?4 ACR-97 SLE criteria were retrospectively investigated for severe infections. Patients with and without infections were compared in terms of SLE severity, damage, comorbidities, and demographic characteristics. A multivariable Cox regression model was built to calculate hazard ratios (HRs) for the first infection. RESULTS: A total of 3658 SLE patients were included: 90% female, median age 32.9 years (DQ 9.7), and mean follow-up (months) 120.2 (±87.6). A total of 705 (19.3%) patients suffered ?1 severe infection. Total severe infections recorded in these patients numbered 1227. The incidence rate was 29.2 (95% CI: 27.6-30.9) infections per 1000 patient years. Time from first infection to second infection was significantly shorter than time from diagnosis to first infection (p < 0.000). Although respiratory infections were the most common (35.5%), bloodstream infections were the most frequent cause of mortality by infection (42.0%). In the Cox regression analysis, the following were all associated with infection: age at diagnosis (HR = 1.016, 95% CI: 1.009-1.023), Latin-American (Amerindian-Mestizo) ethnicity (HR = 2.151, 95% CI: 1.539-3.005), corticosteroids (?10mg/day) (HR = 1.271, 95% CI: 1.034-1.561), immunosuppressors (HR = 1.348, 95% CI: 1.079-1.684), hospitalization by SLE (HR = 2.567, 95% CI: 1.905-3.459), Katz severity index (HR = 1.160, 95% CI: 1.105-1.217), SLICC/ACR damage index (HR = 1.069, 95% CI: 1.031-1.108), and smoking (HR = 1.332, 95% CI: 1.121-1.583). Duration of antimalarial use (months) proved protective (HR = 0.998, 95% CI: 0.997-0.999). CONCLUSIONS: Severe infection constitutes a predictor of poor prognosis in SLE patients, is more common in Latin-Americans and is associated with age, previous infection, and smoking. Antimalarials exerted a protective effect. Spanish Foundation of Rheumatology. FIS/ISCIII (grant number PI11/02857). Dr. Pego-Reigosa is supported by Grant 316265 (BIOCAPS) from the European Union 7th Framework Programme (FP7/REGPOT-2012–2013.1).

The objective of this study is to determine the prevalence of fibromyalgia (FM) in systemic lupus erythematosus (SLE) patients and to study its relationship to depression and other SLE-related factors.A cross-sectional data analysis from the RELESSER-Transversal Spanish Registry, which includes SLE patients in a national multicentre retrospective charts review, was performed.patients who fulfilled ≥4 ACR 1997 SLE criteria. Main variables were disease duration, depression, sociodemographics, comorbidities, SLE activity symptoms, serological findings, therapies and different disease status indices. Statistical analyses included a descriptive, associative and logistic regression analyses. A literature review was performed.3,591 SLE patients were included, 90.1% women, 34.6 years of age at diagnosis (SD 14.6 years) and 93.1% Caucasians. FM prevalence was 6.2%. SLE patients with disease duration5 years showed more FM than those with duration5 years: 6.9% vs. 4.0%, respectively (p0.05). SLE-FM patients showed higher prevalence of depression compared to non-FM-SLE patients: 53.1% vs. 14.6%, respectively (p0.001). After adjusting by risk factors, the OR (CI) of suffering depression in FM-SLE patients was 6.779 (4.770-9.636), p0.001. The OR of having secondary Sjögren's 2.447 (1.662-3.604), p0.001, photosensitivity 2.184 (1.431-3.334), p0.001, and oral ulcers 1.436 (1.005-2.051), p=0.047.Prevalence of FM in Caucasian SLE patients was high compared to the general population, and was significantly higher in those in later stages of disease. SLE patients with depression showed a strong risk of developing FM. Photosensitivity, oral ulcers and secondary Sjögren's were the only SLE-related factors associated with FM.

To assess the efficacy of tocilizumab (TCZ) in giant cell arteritis (GCA) patients with refractory disease and/or with unacceptable side effects due to corticosteroids.A retrospective multicenter open-label study on 22 GCA patients treated with TCZ at standard dose of 8mg/kg/month. The main outcomes were achievement of disease remission and reduction of corticosteroid dose.The mean age ± standard deviation of patients was 69 ± 8 years. The main clinical features at TCZ onset were polymyalgia rheumatica (n = 16), asthenia (n = 7), headache (n =5), constitutional symptoms (n = 4), jaw claudication (n = 2), and visual loss (n = 2). Besides corticosteroids and before TCZ onset, 19 of 22 patients had also received several conventional immunosuppressive and/or biologic drugs. Of 22 patients, 19 achieved rapid and maintained clinical improvement following TCZ therapy. Also, after a median follow-up of 9 (interquartile range: 6-19) months, the C-reactive protein level had fallen from 1.9 (1.2-5.4) to 0.2 (0.1-0.9)mg/dL (p0.0001) and the erythrocyte sedimentation rate decreased from 44 (20-81) to 12 (2-20)mm/1st hour (p = 0.001). The median dose of prednisone was also tapered from 18.75 (10-45) to 5 (2.5-10)mg/day (p0.0001). However, TCZ had to be discontinued in 3 patients due to severe neutropenia, recurrent pneumonia, and cytomegalovirus infection. Moreover, 1 patient died after the second infusion of TCZ due to a stroke in the setting of an infectious endocarditis.TCZ therapy leads to rapid and maintained improvement in patients with refractory GCA and/or with unacceptable side effects related to corticosteroids. However, the risk of infection should be kept in mind when using this drug in patients with GCA.

Objectives: To analyze the usefulness of the new azoles for the treatment of fungal osteoarticular infections, and to report three cases of fungal knee arthritis treated with fluconazole in our unit. Methods: The medical literature was reviewed for all cases of osteoarticular infection caused by fungi and treated with fluconazole or itraconazole registered in the MedLine Silver Platter database from 1972 to 1997. Results: The total number of patients included in this review was 56; 19 weretreated with fluconazole and 37 with itraconazole. The most frequent causative agents implicated were fungi of the genuses Candida and Aspergillus. There were eight therapeutic failures, and there were no statistically different findings among the patients in terms of their health status. Adverse effects were unusual. Conclusions: Controlled studies are necessary to establish the true role of thenew azole drugs in the treatment of fungal osteoarticular infections, but they seem to be a promising therapeutic option.