Damage measured by Damage Index for Antiphospholipid Syndrome (DIAPS) in antiphospholipid antibody-positive patients included in the APS ACTION registry.

OBJECTIVES: Our primary objective was to quantify damage burden measured by Damage Index for Antiphospholipid Syndrome (DIAPS) in aPL-positive patients with or without a history of thrombosis in an international cohort (the APS ACTION cohort). Secondly, we aimed to identify clinical and laboratory characteristics associated with damage in aPL-positive patients. METHODS: In this cross-sectional study, we analysed the baseline damage in aPL-positive patients with or without APS classification. We excluded patients with other autoimmune diseases. We analysed the demographic, clinical and laboratory characteristics based on two subgroups: (i) thrombotic APS patients with high vs low damage; and (ii) non-thrombotic aPL-positive patients with vs without damage. RESULTS: Of the 826 aPL-positive patients included in the registry as of April 2020, 586 with no other systemic autoimmune diseases were included in the analysis (412 thrombotic and 174 non-thrombotic). In the thrombotic group, hyperlipidaemia (odds ratio [OR] 1.82; 95% CI 1.05, 3.15; adjusted P = 0.032), obesity (OR 2.14; 95% CI 1.23, 3.71; adjusted P = 0.007), aß2GPI high titres (OR 2.33; 95% CI 1.36, 4.02; adjusted P = 0.002) and corticosteroid use (ever) (OR 3.73; 95% CI 1.80, 7.75; adjusted P < 0.001) were independently associated with high damage at baseline. In the non-thrombotic group, hypertension (OR 4.55; 95% CI 1.82, 11.35; adjusted P = 0.001) and hyperlipidaemia (OR 4.32; 95% CI 1.37, 13.65; adjusted P = 0.013) were independent predictors of damage at baseline; conversely, single aPL positivity was inversely correlated with damage (OR 0.24; 95% CI 0.075, 0.77; adjusted P = 0.016). CONCLUSIONS: DIAPS indicates substantial damage in aPL-positive patients in the APS ACTION cohort. Selected traditional cardiovascular risk factors, steroids use and specific aPL profiles may help to identify patients more prone to present with a higher damage burden.

ANA-positive versus ANA-negative Antiphospholipid Antibody-positive Patients: Results from the APS ACTION Clinical Database and Repository.

OBJECTIVES: This study focused on the prevalence and impact of antinuclear antibodies (ANA) in antiphospholipid antibody (aPL)-positive patients without concomitant systemic autoimmune rheumatic diseases (SARDs). METHODS: Data from aPL-positive patients with or without Revised Sapporo APS classification criteria were retrieved from the APS ACTION Registry. Patients with concomitant SARDs were excluded. RESULTS: 430 aPL-positive patients were included in the analysis, 56% ANA-positive and 44% negative. ANA positivity was significantly associated with history of hematologic manifestations (persistent autoimmune hemolytic anaemia, thrombocytopenia, leukopenia and/or lymphopenia) (16% of ANA-positive vs 7% of ANA-negative, p= 0.006). Triple aPL-positivity was more frequent in the ANA-positive subgroup (p= 0.02), along with low baseline C3 and C4 levels (p= 0.05 and p= 0.009, respectively), and higher frequency for extractable nuclear antigens (ENA). Among aPL-positive patients with no APS classification, ANA-positive patients showed a higher rate of arthritis (p= 0.006). Among female patients who have experienced at least one pregnancy, 113 were ANA-positive and 96 were ANA-negative; ANA-negative patients had a higher number of pregnancies (p= 0.018), and number of live births (p= 0.014). A wider proportion of ANA-positive patients were treated with hydroxychloroquine (HCQ) (p< 0.001). CONCLUSION: When we analysed aPL-positive patients with no other SARDs, ANA status was not associated with thrombosis or pregnancy morbidity. Interestingly, ANA-positive patients showed higher rates of systemic autoimmune features, including hematologic manifestations, multiple aPL positivity, lower complement levels, ENA positivity, and joint involvement, and were more often treated with HCQ. Finally, aPL-positive subjects who were ANA-negative had a higher rate of pregnancies and live births.

Lack of awareness of systemic lupus erythematosus and its consequences in a cohort of moderate and severe patients in Spain: The LupusVoice study.

BACKGROUND AND OBJECTIVES: Systemic lupus erythematosus (SLE) is an autoimmune condition that can highly impact patients' quality of life (QoL). However, there is a lack of knowledge about SLE, affecting the general population and health care professionals (HCPs) alike. This lack of knowledge has negative implications for patients and the healthcare system, worsening prognosis, negatively impacting QoL, and increasing healthcare utilization. The aim of this paper is to draw attention, according to the perspective of the participants of this study, to the lack of awareness of SLE and its consequences in Spain, and to suggest improvements. PATIENTS AND METHODS: This qualitative, descriptive, observational, multicenter, and cross-sectional study included 40 patients with moderate or severe SLE, recruited during their routine visits in six university hospitals in Spain. The study also included 11 caregivers and 9 HCPs. All participants were individually interviewed. Data from the interviews were coded and analyzed thematically by two anthropologists following a phenomenological perspective. RESULTS: Our study identified a lack of disease awareness among primary care physicians, emergency medicine doctors, and other specialists treating SLE symptomatology. This led to diagnostic delays, which had a clinical and emotional impact on patients. Furthermore, symptom awareness was found to be context dependent. Differences in symptom awareness between HCPs and patients led to a mismatch between the severity evaluation made by doctors and patients. Some HCPs did not consider the limitations of the current severity evaluation of SLE, and therefore attributed symptoms potentially caused by SLE to the unfavorable socioeconomic conditions patients lived in. Finally, a lack of social awareness among friends, family members, and romantic partners led to lower social support, increased isolation, and negative physical and emotional impact for patients. Gender differences in the provision of support were identified. CONCLUSION: This study highlights the need to increase SLE awareness among patients, HCPs, and the broader public in order to improve patient QoL. Being aware of the clinical and emotional impact of such lack of awareness, as well as the role played by context on the patient experience of SLE, is a crucial step towards achieving this goal.

Associations Among Antiphospholipid Antibody Types, Isotypes, and Titers: An AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION) Study.

Several antiphospholipid antibody (aPL) profiles ("triple" and lupus anticoagulant [LA] positivity) are associated with a higher risk for clinical manifestations of antiphospholipid syndrome (APS). Further risk is correlated with higher levels of anticardiolipin antibody (aCL) and anti-ß2 glycoprotein-I antibody (aß2GPI), and with aPL persistence. Given that the 3 aPL tests detect partially overlapping sets of antibodies, the primary goal of this study was to characterize the associations among aPL tests using AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION) core laboratory data. The APS ACTION Registry includes annually followed adult patients with positive aPL based on the Revised Sapporo Classification Criteria. We analyzed baseline and prospective core laboratory data of the registry for associations among aPL tests using the Spearman rank correlation with Bonferroni-adjusted significance level for multiple comparisons. An aPL Load was calculated based on 6 tests (aCL IgG/IgM/IgA and aß2GPI IgG/IgM/IgA); a receiver operating characteristic curve was used to evaluate the diagnostic performance of the aPL Load in predicting LA positivity. In 351 patients simultaneously tested for LA, aCL, and aß2GPI, the frequency of moderate-to-high (≥40 U) titers of aCL and aß2GPI IgG/IgM/IgA was higher in patients who were positive for LA vs those who were negative. An aPL Load was calculated for each patient to assess the overall aPL burden. For every 1-point increase in the aPL Load, the possibility of a positive LA test increased by 32% (odds ratio, 1.32; 95% CI, 1.2-1.5; P < .001). Based on core laboratory data from a large international registry, most aPL enzyme-linked immunosorbent assay ≥40 U and a high calculated aPL Load combining 6 aPL enzyme-linked immunosorbent assays were predictive of a positive LA. These data suggest that the combined quantitative burden of aPL may provide a mechanistic explanation of a positive LA.

Does expert opinion match the definition of lupus low disease activity state? Prospective analysis of 500 patients from a Spanish multicentre cohort.

OBJECTIVES: To apply the lupus low disease activity state (LLDAS) definition within a large cohort of patients and to assess the agreement between the LLDAS and the physician's subjective evaluation of lupus activity. METHODS: We conducted a cross-sectional analysis of a prospective multicentre study of SLE patients. We applied the LLDAS and assessed whether there was agreement with the clinical status according to the physician's opinion. RESULTS: A total of 508 patients [92% women; mean age 50.4 years (s.d. 3.7)] were recruited and 304 (62.7%) patients were in the LLDAS. According to physician assessment, 430 (86.1%) patients were classified as remission or low activity. Overall agreement between both evaluations was 71.4% (95% CI: 70.1, 70.5) with a Cohen's κ of 0.3 [interquartile range (IQR) 0.22-0.37]. Most cases (96.1%) in the LLDAS were classified as remission or low activity by the expert. Of the patients who did not fulfil the LLDAS, 126 (70.4%) were classified as having remission/low disease activity. The main reasons for these discrepancies were the presence of new manifestations compared with the previous visit and a SLEDAI 2K score >4, mainly based on serological activity. CONCLUSIONS: Almost two-thirds of SLE patients were in the LLDAS. There was a fair correlation between the LLDAS and the physician's evaluation. This agreement improves for patients fulfilling the LLDAS criteria. The discordance between both at defining lupus low activity, the demonstrated association of the LLDAS with better outcomes and the fact that the LLDAS is more stringent than the physician's opinion imply that we should use the LLDAS as a treat-to-target goal.

Immunosuppression use in primary antiphospholipid antibody-positive patients: Descriptive analysis of the AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION) Clinical Database and Repository ("Registry").

BACKGROUND/PURPOSE: APS ACTION Registry was created to study the outcomes of patients with persistently positive antiphospholipid antibodies (aPL) with or without other systemic autoimmune disease (SAIDx). Given that immunosuppression (IS) is used for certain aPL manifestations, for example, thrombocytopenia (TP), our primary objective was to describe the indications for IS in aPL-positive patients without other SAIDx. Secondly, we report the type of IS used in patients with selected microvascular or non-thrombotic aPL manifestations. METHODS: An online database is used to collect clinical data. The inclusion criteria are positive aPL based on the laboratory section of the APS Classification Criteria, tested at least twice within one year prior to enrollment. Patients are followed every 12 ± 3 months. For this descriptive retrospective and prospective analysis, we included aPL-positive patients without other SAIDx and excluded those with new SAIDx classification during follow-up. For each patient, we retrieved clinical data at baseline and follow-up including selected aPL manifestations (diffuse alveolar hemorrhage [DAH], antiphospholipid-nephropathy [aPL-N], livedoid vasculopathy [LV]-related skin ulcers, TP, autoimmune hemolytic anemia [AIHA], cardiac valve disease [VD]), and IS medications. RESULTS: Of 899 patients enrolled, 537 were included in this analysis (mean age 45 ± 13 years, female 377 [70%], APS Classification in 438 [82%], and at least one selected microvascular or non-thrombotic aPL manifestation in 141 (26%)). Of 537 patients, 76 (14%) were reported to use IS (ever), and 41/76 (54%) received IS primarily for selected aPL manifestation. In six of 8 (75%) DAH patients, 6/19 (32%) aPL-N, 4/28 (14%) LV, 25/88 (28%) TP, 6/11 (55%) AIHA, and 1/43 (2%) VD, the IS (excluding corticosteroids/hydroxychloroquine) indication was specific for selected aPL manifestation. CONCLUSION: In our international cohort, 14% of aPL-positive patients without other SAIDx were reported to receive IS; the indication was at least one of the selected microvascular and/or non-thrombotic aPL-related manifestations in half. Thrombocytopenia was the most frequent among those selected aPL-related manifestations; however, approximately one-third received IS specifically for that indication. Diffuse alveolar hemorrhage was frequently treated with IS followed by AIHA and aPL-N. Systematic controlled studies are urgently needed to better define the role of IS in APS.

Something new about prognostic factors for lupus nephritis? A systematic review.

BACKGROUND: Lupus nephritis (LN) affects 30-45% of patients with systemic lupus erythematosus (SLE) and causes great morbidity and mortality. About 10-25% of patients will develop chronic kidney disease (CKD), and it has been described a mortality of 10-20% at 10 years. The contribution of clinical and biological markers to the prediction of outcome is unclear. OBJECTIVE: To describe the factors, with measures of association, that predict the main outcomes of LN. MATERIAL AND METHODS: We have conducted a systematic review. Medline, Embase, and Cochrane Library were systematic searched from inception up to Oct 2019, with a strategy that included synonyms of all targeted outcomes of LN: (kidney failure, response to treatment, cardiovascular events, and mortality). Only studies with longitudinal prospective design or with warranties of unbiased recollection of the prognostic factors, where LN was confirmed by biopsy were included. Risk of bias was assessed with the New Castle Ottawa scale. Predictive factors and their effect measures were collected from each study. RESULTS: From 1221 studies identified, 25 studies were included, of which 15 were retrospective, nine prospective, and one was a trial extension study (range from 3 months to 11 years). The main predictive factors of renal response were serum creatinine (SCr) and glomerular filtration rate C3 levels, titer of anti-C1q, and anti-dsDNA antibodies. Renal histological findings such as class type (IV or V), tubulointerstitial or vascular lesions and chronicity index were risk factors for development of chronic kidney disease. The factors associated with persistence of activity were proteinuria, anti-dsDNA, anticardiolipin, anti C1q antibodies, and complement values. The factors associated to cardiovascular events and mortality were age, smoking, amount of proteinuria, and histological findings, such as vascular lesions. Meta-analysis was precluded given the heterogeneity of designs definitions and effect measures. CONCLUSIONS: Nowadays, we do not have new biomarkers that establish the renal prognosis of patients with LN. Classical clinical, renal, and histological markers are used in most studies. It is worth noting the heterogeneity of studies in the definition of renal outcomes, which complicates risk stratification in these patients.

Implementation of an assessment checklist for patients with spondyloarthritis in daily practice.

OBJECTIVES: To analyse the feasibility and changes in the collection of clinical measures after the implementation in daily practice of a checklist designed for an optimal evaluation and monitoring of patients with spondyloarthritis (SpA). METHODS: An observational prospective study was performed. The feasibility of the assessment checklist (paper/on-line format) for patients with SpA was tested (time to complete the checklist, simplicity, amenity clarity, usefulness). Through a medical files review, changes in the number of the checklist variables collected were analysed previous to the implementation of the checklist and 6 months later. A descriptive and bivariate analysis was performed. RESULTS: A total 6 hospitals and 11 rheumatologists participated. The median time to checklist completion was 15 (12-20) minutes, and the mean scores for the rest of variables of the feasibility test were in general positives. A total of 83 and 68 medical files pre-implementation and post-implementation were reviewed respectively. We observed a significant increase in the collection of many of the checklist variables after the implementation. The record of BASDAI increased from 46.2% to 73.1% (p=0.001), physical activity from 48.2% to 88.2% (p<0.0001), physician global (VAS) from 28.0% to 73.5% (p<0.0001), patient global (VAS) from 48.8% to 85.3% (p<0.0001), morning stiffness from 62.8% to 84.8% (p=0.003), ASDAS from 12.2% to 32.8% (p=0.002), BASFI from 43.7% to 65.7% (p=0.008), or DAS28 from 24.7% to 46.3% (p=0.006). These changes were observed irrespectively of SpA classification. CONCLUSIONS: The implementation of an assessment checklist in daily practice is feasible and improves the assessment of SpA patients.

Thrombosis recurrence and major bleeding in non-anticoagulated thrombotic antiphospholipid syndrome patients: Prospective study from antiphospholipid syndrome alliance for clinical trials and international networking (APS ACTION) clinical database and repository ("Registry").

BACKGROUND: Long-term anticoagulant therapy is generally recommended for thrombotic antiphospholipid syndrome (TAPS) patients, however it may be withdrawn or not introduced in routine practice. OBJECTIVES: To prospectively evaluate the risk of thrombosis recurrence and major bleeding in non-anticoagulated TAPS patients, compared to anticoagulated TAPS, and secondly, to identify different features between those two groups. PATIENTS/METHODS: Using an international registry, we identified non-anticoagulated TAPS patients at baseline, and matched them with anticoagulated TAPS patients based on gender, age, type of previous thrombosis, and associated autoimmune disease. Thrombosis recurrence and major bleeding were prospectively analyzed using Kaplan-Meier method and compared using a marginal Cox's regression model. RESULTS: As of June 2022, 94 (14 %) of the 662 TAPS patients were not anticoagulated; and 93 of them were matched with 181 anticoagulated TAPS patients (median follow-up 5 years [interquartile range 3 to 8]). The 5-year thrombosis recurrence and major bleeding rates were 12 % versus 10 %, and 6 % versus 7 %, respectively (hazard ratio [HR] 1.38, 95 % confidence interval [CI] 0.53 to 3.56, p = 0.50 and HR 0.53; 95 % CI 0.15 to 1.86; p = 0.32, respectively). Non-anticoagulated patients were more likely to receive antiplatelet therapy (p < 0.001), and less likely to have more than one previous thrombosis (p < 0.001) and lupus anticoagulant positivity (p = 0.01). CONCLUSION: Fourteen percent of the TAPS patients were not anticoagulated at recruitment. Their recurrent thrombosis risk did not differ compared to matched anticoagulated TAPS patients, supporting the pressing need for risk-stratified secondary thrombosis prevention trials in APS investigating strategies other than anticoagulation.

Anti-Neutrophil Extracellular Trap Antibodies in Antiphospholipid Antibody-Positive Patients: Results From the Antiphospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking Clinical Database and Repository.

OBJECTIVE: This study aimed to elucidate the presence, antigen specificities, and potential clinical associations of anti-neutrophil extracellular trap (anti-NET) antibodies in a multinational cohort of antiphospholipid (aPL) antibody-positive patients who did not have lupus. METHODS: Anti-NET IgG/IgM levels were measured in serum samples from 389 aPL-positive patients; 308 patients met the classification criteria for antiphospholipid syndrome. Multivariate logistic regression with best variable model selection was used to determine clinical associations. For a subset of the patients (n = 214), we profiled autoantibodies using an autoantigen microarray platform. RESULTS: We found elevated levels of anti-NET IgG and/or IgM in 45% of the aPL-positive patients. High anti-NET antibody levels are associated with more circulating myeloperoxidase (MPO)-DNA complexes, which are a biomarker of NETs. When considering clinical manifestations, positive anti-NET IgG was associated with lesions affecting the white matter of the brain, even after adjusting for demographic variables and aPL profiles. Anti-NET IgM tracked with complement consumption after controlling for aPL profiles; furthermore, patient serum samples containing high levels of anti-NET IgM efficiently deposited complement C3d on NETs. As determined by autoantigen microarray, positive testing for anti-NET IgG was significantly associated with several autoantibodies, including those recognizing citrullinated histones, heparan sulfate proteoglycan, laminin, MPO-DNA complexes, and nucleosomes. Anti-NET IgM positivity was associated with autoantibodies targeting single-stranded DNA, double-stranded DNA, and proliferating cell nuclear antigen. CONCLUSION: These data reveal high levels of anti-NET antibodies in 45% of aPL-positive patients, where they potentially activate the complement cascade. While anti-NET IgM may especially recognize DNA in NETs, anti-NET IgG species appear to be more likely to target NET-associated protein antigens.

Comparative results of the implementation in daily practice of an evaluation checklist for patients with axial spondyloarthritis and psoriatic arthritis.

OBJECTIVE: To analyse and compare changes in the collection of clinical variables after the implementation in daily practice of an evaluation checklist for patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). METHODS: An observational study was performed based on medical records review. The number and type of variables of the evaluation checklist in the medical records were collected. The first review was made before the implementation of the checklist, and the second one 6 months after the implementation (in different patients). A descriptive and bivariate analysis was carried out. RESULTS: Six hospitals and 11 rheumatologists participated. A total of 83 and 68 medical records were reviewed before and after the implementation of the checklist. After the implementation, in the axSpA patients, a significant increase was recorded in alcohol consumption, diarrhoea or IBD and urethritis, diabetes mellitus, hyperlipidaemia, depression, obesity or gout/hyperuricaemia, weight, height, blood pressure, patient and physician global assessments of disease activity, BASDAI and DAS28. And, in the PsA patients, alcohol consumption, hypertension, diabetes mellitus, hyperlipidaemia, disease, gout/hyperuricaemia, thoracic expansion, cervical rotation, weight, height, blood pressure, patient and physician global assessments of disease, ASDAS, BASDAI, and BASFI were recorded. In general, there was a trend towards greater recording in axSpA compared with PsA. CONCLUSIONS: The implementation of a specific checklist in daily practice improves the evaluation of patients with axSpA and PsA. More efforts are necessary to continue improving the evaluation of patients with axSpA, but especially of those with PsA.

Pregnancy control in Patients with Systemic Lupus Erythematosus/Antiphospholipid Syndrome. Part 3: Childbirth. Puerperium. Breastfeeding Contraception. Newborn. / Control del embarazo en pacientes con lupus eritematoso sistémico/síndrome antifosfolípido. Parte 3. Parto. Puerperio. Lactancia. Anticoncepción. Recién nacido.

OBJECTIVE: In order to agree on the fundamental aspects related to the management of pregnancy in patients with systemic lupus erythematosus and antiphospholipid syndrome, the Spanish Societies of Gynaecology and Obstetrics, Internal Medicine and Rheumatology have set up a working group for the preparation of three consensus documents. METHODS: Each of the Scientific Societies involved proposed five representatives based on their experience in the field of pregnancy control in patients with autoimmune diseases. The recommendations were developed following the Delphi methodology. RESULTS: This third document contains the recommendations regarding the management of delivery, puerperium and lactation, including medication use during these periods and the care of the newborn. In addition, a section on contraception is included. CONCLUSIONS: These multidisciplinary recommendations are considered decision-making tools for clinicians involved in the care of patients with systemic lupus erythematosus/antiphospholipid syndrome during pregnancy.

Pregnancy control in patients with systemic lupus erythematosus/antiphospholipid syndrome. Part 2: Pregnancy follow-up. / Control del embarazo en pacientes con lupus eritematoso sistémico/síndrome antifosfolípido. parte 2: seguimiento del embarazo.

OBJECTIVE: In order to agree on the fundamental aspects related to the management of pregnancy in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS), the Spanish Societies of Gynaecology and Obstetrics, Internal Medicine and Rheumatology set up a working group for the preparation of three consensus documents. METHODS: Each of the Scientific Societies involved proposed five representatives based on their experience in the field of pregnancy control in patients with autoimmune diseases. The recommendations were developed following the Delphi methodology. RESULTS: This second document contains the recommendations regarding the management of pregnancy in women with SLE and APS, including complications such as lupus activity, congenital heart block, thrombotic and obstetric manifestations of APS and placental vascular disease. CONCLUSIONS: These multidisciplinary recommendations are considered decision-making tools for clinicians involved in the care of patients with SLE/APS during pregnancy.

Pregnancy Control in Patients with Systemic Lupus Erythematosus and Antiphospholipid Syndrome. Part 1: Infertility, Ovarian Preservation and Preconception Assessment. Consensus Document of the Spanish Society of Gynaecology and Obstetrics (SEGO), the Spanish Society of Internal Medicine (SEMI) and the Spanish Society of Rheumatology (SER). / Control del embarazo en pacientes con lupus eritematoso sistémico y síndrome antifosfolípido. Parte 1: Infertilidad, preservación ovárica y valoración preconcepcional. Documento de consenso de la Sociedad Española de Ginecología y Obstetricia (SEGO), Sociedad Española de Medicina Interna (SEMI) y Sociedad Española de Reumatología (SER).

OBJECTIVE: Pregnancy and puerperium are considered a risk situation in women with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Therefore, specialized assessment is essential both preconception and during pregnancy and the puerperium. Likewise, it is very important that different specialists in autoimmune diseases and high-risk pregnancies participate in the follow-up of these patients in a coordinated manner. The Spanish Society of Gynaecology and Obstetrics, the Spanish Society of Internal Medicine, and the Spanish Society of Rheumatology have set up a working group for the preparation of three consensus documents. METHODS: The stages of the work were: distribution of work in three groups corresponding to the three periods related to pregnancy (preconception, during pregnancy and childbirth and puerperium), identification of key areas, exhaustive review of the literature and formulation of recommendations. RESULTS: This first document includes the 48 recommendations that address aspects related to infertility, the need for and treatments for gonadal preservation and preconception assessment. CONCLUSIONS: These multidisciplinary recommendations are considered decision-making tools for clinicians involved in the care of patients with SLE/APS during pregnancy.

Genome-wide association study meta-analysis identifies five new loci for systemic lupus erythematosus.

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.

Resultados comparativos de la implementación en práctica diaria de un checklist de evaluación para pacientes con espondiloartritis axial y artritis psoriásica / Comparative results of the implementation in daily practice of an evaluation checklist for patients with axial spondyloarthritis and psoriatic arthritis

Objetivo: Analizar y comparar los cambios en la recogida de variables clínicas tras la implementación en la práctica diaria de un checklist de evaluación para pacientes con espondiloartritis axial (EspAax) y artritis psoriásica (APs). Métodos: Se realizó un estudio observacional. Mediante revisión de historias médicas, se recogieron el número y el tipo de variables del checklist de evaluación que figuraban en las mismas. La primera revisión se realizó antes de la implementación del checklist, y la segunda, 6meses después de la implementación (pacientes diferentes) para poder comparar los cambios producidos con la misma. Se realizó un análisis descriptivo y bivariado. Resultados: Participaron 6 hospitales y 11 reumatólogos. Se revisaron un total de 83 y 68 historias médicas pre- y post-implementación del checklist. Tras la implementación, en la EspAax aumentó significativamente el registro en la historia clínica del consumo de alcohol, diarrea o enfermedad inflamatoria intestinal (EII) y la uretritis, diabetes mellitus, hiperlipidemia, depresión, obesidad o la gota/hiperuricemia, peso, talla, presión arterial, VGM, VGP, BASDAI y DAS28. Y en la APs el consumo de alcohol, HTA, diabetes mellitus, hiperlipidemia, enfermedad, gota/hiperuricemia, expansión torácica, rotación cervical, peso, talla, presión arterial, VGM, VGP, ASDAS, BASDAI y BASFI. Tanto pre- como post-implantación en general existe una tendencia a un mayor porcentaje de recogida de variables en pacientes con EspAax que en pacientes con APs. Conclusiones: La implementación de un checklist específico en la práctica diaria mejora la evaluación de los pacientes con EspAax y APs. Se debe seguir trabajando en la mejoría de la evaluación de los pacientes con EspA, pero especialmente en la APs.(AU)

Objective: To analyse and compare changes in the collection of clinical variables after the implementation in daily practice of an evaluation checklist for patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). Methods: An observational study was performed based on medical records review. The number and type of variables of the evaluation checklist in the medical records were collected. The first review was made before the implementation of the checklist, and the second one 6months after the implementation (in different patients). A descriptive and bivariate analysis was carried out. Results: Six hospitals and 11 rheumatologists participated. A total of 83 and 68 medical records were reviewed before and after the implementation of the checklist. After the implementation, in the axSpA patients, a significant increase was recorded in alcohol consumption, diarrhoea or IBD and urethritis, diabetes mellitus, hyperlipidaemia, depression, obesity or gout/hyperuricaemia, weight, height, blood pressure, patient and physician global assessments of disease activity, BASDAI and DAS28. And, in the PsA patients, alcohol consumption, hypertension, diabetes mellitus, hyperlipidaemia, disease, gout/hyperuricaemia, thoracic expansion, cervical rotation, weight, height, blood pressure, patient and physician global assessments of disease, ASDAS, BASDAI, and BASFI were recorded. In general, there was a trend towards greater recording in axSpA compared with PsA. Conclusions: The implementation of a specific checklist in daily practice improves the evaluation of patients with axSpA and PsA. More efforts are necessary to continue improving the evaluation of patients with axSpA, but especially of those with PsA.(AU)

Control del embarazo en pacientes con lupus eritematoso sistémico/síndrome antifosfolípido. parte 2: seguimiento del embarazo / Pregnancy control in patients with systemic lupus erythematosus/antiphospholipid syndrome. Part 2: Pregnancy follow-up

Objetivo: Las sociedades españolas de ginecología y obstetricia, de medicina interna y de reumatología han constituido un grupo de trabajo paritario para la elaboración de 3 documentos de consenso sobre el control del embarazo en mujeres con lupus eritematoso sistémico (LES) y síndrome antifosfolípido (SAF). Métodos: Cada una de las sociedades científicas implicadas propuso 5 representantes en base a su experiencia en el área del control del embarazo en pacientes con enfermedades autoinmunes. Las recomendaciones se elaboraron siguiendo la metodología Delphi. Resultados: En este segundo documento se incluyen las recomendaciones que abordan el manejo del embarazo normal y sus complicaciones en mujeres con LES/SAF. Se presentan las recomendaciones relacionadas con el seguimiento del embarazo, la actividad lúpica, el bloqueo cardíaco congénito, las manifestaciones trombóticas y obstétricas del SAF y los defectos de placentación. Conclusiones: Estas recomendaciones multidisciplinares se consideran herramientas en la toma de decisiones para los clínicos involucrados en la asistencia a pacientes con LES/SAF durante el embarazo.(AU)

Objective: In order to agree on the fundamental aspects related to the management of pregnancy in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS), the Spanish Societies of Gynaecology and Obstetrics, Internal Medicine and Rheumatology set up a working group for the preparation of three consensus documents. Methods: Each of the Scientific Societies involved proposed five representatives based on their experience in the field of pregnancy control in patients with autoimmune diseases. The recommendations were developed following the Delphi methodology. Results: This second document contains the recommendations regarding the management of pregnancy in women with SLE and APS, including complications such as lupus activity, congenital heart block, thrombotic and obstetric manifestations of APS and placental vascular disease. Conclusions:These multidisciplinary recommendations are considered decision-making tools for clinicians involved in the care of patients with SLE/APS during pregnancy.(AU)

Control del embarazo en pacientes con lupus eritematoso sistémico/síndrome antifosfolípido. Parte 3. Parto. Puerperio. Lactancia. Anticoncepción. Recién nacido / Pregnancy control in Patients with Systemic Lupus Erythematosus/Antiphospholipid Syndrome. Part 3: Childbirth. Puerperium. Breastfeeding Contraception. Newborn

Objetivo: Las Sociedades Españolas de Ginecología y Obstetricia, de Medicina Interna y de Reumatología han constituido un grupo de trabajo paritario para la elaboración de tres documentos de consenso sobre el control del embarazo en mujeres con lupus eritematoso sistémico y síndrome antifosfolípido. Métodos: Cada una de las sociedades científicas implicadas propuso cinco representantes en base a su experiencia en el área del control del embarazo en pacientes con enfermedades autoinmunes. Las recomendaciones se elaboraron siguiendo la metodología Delphi.Resultados: En este tercer documento se incluyen las recomendaciones que abordan el manejo del parto, puerperio y lactancia, incluyendo el manejo de los diferentes fármacos en estos periodos. Además se incluye una sección sobre los cuidados iniciales del recién nacido y sobre anticoncepción. Conclusiones: Estas recomendaciones multidisciplinares se consideran herramientas en la toma de decisiones para los clínicos involucrados en la asistencia a pacientes con lupus eritematoso sistémico/síndrome antifosfolípido durante el embarazo.(AU)

Objective: In order to agree on the fundamental aspects related to the management of pregnancy in patients with systemic lupus erythematosus and antiphospholipid syndrome, the Spanish Societies of Gynaecology and Obstetrics, Internal Medicine and Rheumatology have set up a working group for the preparation of three consensus documents. Methods: Each of the Scientific Societies involved proposed five representatives based on their experience in the field of pregnancy control in patients with autoimmune diseases. The recommendations were developed following the Delphi methodology. Results: This third document contains the recommendations regarding the management of delivery, puerperium and lactation, including medication use during these periods and the care of the newborn. In addition, a section on contraception is included. Conclusions: These multidisciplinary recommendations are considered decision-making tools for clinicians involved in the care of patients with systemic lupus erythematosus/antiphospholipid syndrome during pregnancy.(AU)

Control del embarazo en pacientes con lupus eritematoso sistémico y síndrome antifosfolípido. Parte 1: Infertilidad, preservación ovárica y valoración preconcepcional. Documento de consenso de la Sociedad Española de Ginecología y Obstetricia (SEGO), Sociedad Española de Medicina Interna (SEMI) y Sociedad Española de Reumatología (SER) / Pregnancy Control in Patients with Systemic Lupus Erythematosus and Antiphospholipid Syndrome. Part 1: Infertility, Ovarian Preservation and Preconception Assessment. Consensus Document of the Spanish Society of Gynaecology and Obstetrics (SEGO), the Spanish Society of Internal Medicine (SEMI) and the Spanish Society of Rheumatology (SER)

Objetivo: El embarazo y el puerperio se consideran una situación de riesgo en mujeres con lupus eritematoso sistémico (LES) y síndrome antifosfolípido (SAF). Es esencial que especialistas en enfermedades autoinmunes y en embarazo de alto riesgo intervengan en su seguimiento de forma coordinada. La Sociedad Española de Ginecología y Obstetricia, la Sociedad Española de Medicina Interna, y la Sociedad Española de Reumatología han constituido un grupo de trabajo paritario para la elaboración de 3 documentos de consenso. Métodos: Las fases del trabajo fueron: distribución del trabajo en grupos correspondientes a los 3 períodos relacionados con la gestación, identificación de áreas clave, revisión de la literatura y formulación de recomendaciones. Resultados: En este primer documento se incluyen las primeras 48 recomendaciones que tratan aspectos relacionados con la infertilidad, la necesidad y los tratamientos de preservación gonadal y la valoración preconcepcional. Conclusiones: Estas recomendaciones multidisciplinares se consideran herramientas en la toma de decisiones para los clínicos involucrados en la asistencia a pacientes con LES/SAF durante el embarazo.(AU)

Objective: Pregnancy and puerperium are considered a risk situation in women with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Therefore, specialized assessment is essential both preconception and during pregnancy and the puerperium. Likewise, it is very important that different specialists in autoimmune diseases and high-risk pregnancies participate in the follow-up of these patients in a coordinated manner. The Spanish Society of Gynaecology and Obstetrics, the Spanish Society of Internal Medicine, and the Spanish Society of Rheumatology have set up a working group for the preparation of three consensus documents. Methods: The stages of the work were: distribution of work in three groups corresponding to the three periods related to pregnancy (preconception, during pregnancy and childbirth and puerperium), identification of key areas, exhaustive review of the literature and formulation of recommendations. Results: This first document includes the 48 recommendations that address aspects related to infertility, the need for and treatments for gonadal preservation and preconception assessment. Conclusions: These multidisciplinary recommendations are considered decision-making tools for clinicians involved in the care of patients with SLE/APS during pregnancy.(AU)

Characterization of Patients With Lupus Nephritis Included in a Large Cohort From the Spanish Society of Rheumatology Registry of Patients With Systemic Lupus Erythematosus (RELESSER).

The aim of the study was to profile those patients included in the RELESSER registry with histologically proven renal involvement in order to better understand the current state of lupus nephritis (LN) in Spain. RELESSER-TRANS is a multicenter cross-sectional registry with an analytical component. Information was collected from the medical records of patients with systemic lupus erythematosus who were followed at participating rheumatology units. A total of 359 variables including demographic data, clinical manifestations, disease activity, severity, comorbidities, LN outcome, treatments, and mortality were recorded. Only patients with a histological confirmation of LN were included. We performed a descriptive analysis, chi-square or Student's t tests according to the type of variable and its relationship with LN. Odds ratio and confidence intervals were calculated by using simple logistic regression. LN was histologically confirmed in 1092/3575 patients (30.5%). Most patients were female (85.7%), Caucasian (90.2%), and the mean age at LN diagnosis was 28.4 ±â€Š12.7 years. The risk for LN development was higher in men (M/F:47.85/30.91%, P < 0.001), in younger individuals (P < 0.001), and in Hispanics (P = 0.03). Complete response to treatment was achieved in 68.3% of patients; 10.35% developed ESRD, which required a kidney transplant in 45% of such cases. The older the patient, the greater was the likelihood of complete response (P < 0.001). Recurrences were associated with persistent lupus activity at the time of the last visit (P < 0.001) and with ESRD (P < 0.001). Thrombotic microangiopathy was a risk factor for ESRD (P = 0.04), as for the necessity of dialysis (P = 0.01) or renal transplantation (P = 0.03). LN itself was a poor prognostic risk factor of mortality (OR 2.4 [1.81-3.22], P < 0.001). Patients receiving antimalarials had a significantly lower risk of developing LN (P < 0.001) and ESRD (P < 0.001), and responded better to specific treatments for LN (P = 0.014). More than two-thirds of the patients with LN from a wide European cohort achieved a complete response to treatment. The presence of positive anti-Sm antibodies was associated with a higher frequency of LN and a decreased rate of complete response to treatment. The use of antimalarials reduced both the risk of developing renal disease and its severity, and contributed to attaining a complete renal response.