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Introduction: Diffuse alveolar hemorrhage (DAH) is a rare complication with high mortality in patients with systemic lupus erythematosus (SLE). Early diagnosis and treatment are essential to improve patient prognosis. To determine the characteristics of patients with DAH and their mortality in a Spanish cohort of patients with SLE., Methods: Patients from the RELESSER (Spanish Society of Rheumatology Lupus Register) who had had at least one confirmed episode of DAH were included. Epidemiological, clinical, and laboratory characteristics were analyzed., Results: 4024 patients were included in the RELESSER register, 37 (0.9%), had at least one recorded episode of DAH. Only further data for 14 patients could be analyzed. In total, 92.9% were women, and for 4 (28.6%) DAH coincided with the debut of SLE. More than 80% of patients had renal involvement and thrombocytopenia. The most frequent manifestations were dyspnea (85.7%) and hypoxemia (100%), with the classic triad of hemoptysis, anemia and pulmonary infiltrates, appearing in 6 (46.2%) patients. The most frequently used treatments were glucocorticoids (85.7%) and cyclophosphamide (69.2%); plasmapheresis was utilized in 5 patients (35.7%) and 8, (57.1%) received intravenous immunoglobulins; 12 (85.7%) patients required admission to the ICU and 5 (35.7%) died. Tobacco use, history of lupus nephritis (LN), concomitant infection, and treatment with cyclophosphamide were more frequent in patients who died., Conclusions: DAH is rare in patients with SLE; in up to one-third of patients, it may appear at the onset of the disease. Some factors, such as smoking, a history of LN, treatment with cyclophosphamide, or concomitant infection, are more prevalent in patients with an unfavorable outcome., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To compare the safety of Janus kinase inhibitors (JAKi) with that of tumour necrosis factor inhibitors (TNFi) and determine drug persistence among patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA)., Methods: We analysed data from patients included in BIOBADASER 3.0 and treated with JAKi or TNFi from 2015 to 2023 and estimated the incidence rate ratio (IRR) of adverse events and persistence., Results: A total of 6826 patients were included. Of these, 52% had RA, 25% psoriatic arthritis and 23% axial SpA. Treatment was with TNFi in 86%. The mean duration of treatment was 2.2±2.0 years with TNFi versus 1.8±1.5 with JAKi. JAKis were prescribed in older patients with longer term disease, greater comorbidity and later treatment lines and more frequently as monotherapy. The IRR of all infections and gastrointestinal events was higher among patients with RA treated with JAKi. Drug persistence at 1, 2 and 3 years was 69%, 55% and 45% for TNFi and 68%, 54% and 45% for JAKi. Multivariate regression models showed a lower probability of discontinuation for JAKi (HR=0.85; 95% CI 0.78-0.92) and concomitant conventional synthetic disease-modifying antirheumatic drugs (HR=0.90; 95% CI 0.84-0.96). The risk of discontinuation increased with glucocorticoids, comorbidities, greater disease activity and later treatment lines., Conclusions: Infections, herpes zoster and gastrointestinal adverse events in patients with RA tended to be more frequent with JAKi. However, prognosis was poor in patients receiving JAKi. Persistence was similar for TNFi and JAKi, although factors associated with discontinuation differed by diagnostic group., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Objective: To assess organ damage, with emphasis on the cardiovascular system, over the different stages of the disease in a large SLE cohort., Methods: Multicentre, longitudinal study of a cohort of 4219 patients with SLE enrolled in the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). We longitudinally analysed SDI (globally and for each domain) over time only in the 1274 patients whose dates of damage events had been recorded., Results: During the first year after diagnosis of SLE, 20% of the 1274 patients presented with new damage manifestations. At years 2 and 3, new damage was recorded in 11% and 9% of patients. The annual percentage of patients with new damage after year 5 decreased to 5%. In the first year with the disease, most damage was accumulated in the musculoskeletal, neuropsychiatric and renal systems; in later stages, most damage was in the musculoskeletal, ocular and cardiovascular systems. Considering 'cerebrovascular accident' and 'claudication for 6 months' as cardiovascular items, the cardiovascular system was the second most affected system during the early stages of SLE, with 19% of the patients who presented with damage affected at first year after diagnosis. During the late stages, 20-25% of the patients presenting with new damage did so in this modified cardiovascular domain of the SDI., Conclusions: New damage occurs mainly during the first year following diagnosis of SLE. Cardiovascular damage is relevant in both the early and the late stages of the disease. Strategies to prevent cardiovascular damage should be implemented early after diagnosis of SLE., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objective: To develop an improved score for prediction of severe infection in patients with systemic lupus erythematosus (SLE), namely, the SLE Severe Infection Score-Revised (SLESIS-R) and to validate it in a large multicentre lupus cohort., Methods: We used data from the prospective phase of RELESSER (RELESSER-PROS), the SLE register of the Spanish Society of Rheumatology. A multivariable logistic model was constructed taking into account the variables already forming the SLESIS score, plus all other potential predictors identified in a literature review. Performance was analysed using the C-statistic and the area under the receiver operating characteristic curve (AUROC). Internal validation was carried out using a 100-sample bootstrapping procedure. ORs were transformed into score items, and the AUROC was used to determine performance., Results: A total of 1459 patients who had completed 1 year of follow-up were included in the development cohort (mean age, 49±13 years; 90% women). Twenty-five (1.7%) had experienced ≥1 severe infection. According to the adjusted multivariate model, severe infection could be predicted from four variables: age (years) ≥60, previous SLE-related hospitalisation, previous serious infection and glucocorticoid dose. A score was built from the best model, taking values from 0 to 17. The AUROC was 0.861 (0.777-0.946). The cut-off chosen was ≥6, which exhibited an accuracy of 85.9% and a positive likelihood ratio of 5.48., Conclusions: SLESIS-R is an accurate and feasible instrument for predicting infections in patients with SLE. SLESIS-R could help to make informed decisions on the use of immunosuppressants and the implementation of preventive measures., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Obstetric complications are more common in women with systemic lupus erythematosus (SLE) than in the general population., Objective: To assess pregnancy outcomes in women with SLE from the RELESSER cohort after 12 years of follow-up., Methods: A multicentre retrospective observational study was conducted. In addition to data from the RELESSER register, data were collected on obstetric/gynaecological variables and treatments received. The number of term pregnancies was compared between women with pregnancies before and after the diagnosis of SLE. Further, clinical and laboratory characteristics were compared between women with pregnancies before and after the diagnosis, on the one hand, and with and without complications during pregnancy, on the other. Bivariate and multivariate analyses were carried out to identify factors potentially associated with complications during pregnancy., Results: A total of 809 women were included, with 1869 pregnancies, of which 1395 reached term. Women with pregnancies before the diagnosis of SLE had more pregnancies (2.37 vs 1.87) and a higher rate of term pregnancies (76.8% vs 69.8%, p < 0.001) compared to those with pregnancies after the diagnosis. Women with pregnancies before the diagnosis were diagnosed at an older age (43.4 vs 34.1 years) and had more comorbidities. No differences were observed between the groups with pregnancies before and after diagnosis in antibody profile, including anti-dsDNA, anti-Sm, anti-Ro, anti-La, lupus anticoagulant, anticardiolipin or anti-beta-2-glycoprotein. Overall, 114 out of the 809 women included in the study experienced complications during pregnancy, including miscarriage, preeclampsia/eclampsia, foetal death, and/or preterm birth. Women with complications had higher rates of antiphospholipid syndrome (40.5% vs 9.9%, p < 0.001) and higher rates of positivity for IgG anticardiolipin (33.9% vs 21.3%, p = 0.005), IgG anti-beta 2 glycoprotein (26.1% vs 14%, p = 0.007), and IgM anti-beta 2 glycoprotein (26.1% vs 16%, p = 0.032) antibodies, although no differences were found regarding lupus anticoagulant. Among the treatments received, only heparin was more commonly used by women with pregnancy complications. We did not find differences in corticosteroid or hydroxychloroquine use., Conclusions: The likelihood of term pregnancy is higher before the diagnosis of SLE. In our cohort, positivity for anticardiolipin IgG and anti-beta-2- glycoprotein IgG/IgM, but not lupus anticoagulant, was associated with a higher risk of poorer pregnancy outcomes., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflicts of interest associated with this original article., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To investigate the influence of COVID-19 vaccination on disease activity in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients under targeted therapies., Patients and Methods: 1765 vaccinated patients COVID-19, 1178 (66.7%) with RA and 587 (33.3%) with PsA from the COVID-19 registry in patients with rheumatic diseases (COVIDSER) project, were included. Demographics, disease characteristics, Disease Activity Score in 28 joints (DAS28) and targeted treatments were collected. DAS28-based flare rates and categorised disease activity distribution prevaccination and post vaccination were analysed by log-linear regression and contingency analyses, respectively. The influence of vaccination on DAS28 variation as a continuous measure was evaluated using a random coefficient model., Results: The distribution of categorised disease activity and flare rates was not significantly modified by vaccination. Log-linear regression showed no significant changes in the rate of flares in the 6-month period after vaccination compared with the same period prior to vaccination in neither patients with RA nor patients with PsA. When DAS28 variations were analysed using random coefficient models, no significant variations in disease activity were detected after vaccination for both groups of patients. However, patients with RA treated with Janus kinase inhibitors (JAK-i) (1) and interleukin-6 inhibitor (IL-6-i) experienced a worsening of disease activity (1.436±0.531, p=0.007, and 1.201±0.550, p=0.029, respectively) in comparison with those treated with tumour necrosis factor inhibitor (TNF-i). Similarly, patients with PsA treated with interleukin-12/23 inhibitor (IL-12/23-i) showed a worsening of disease activity (4.476±1.906, p=0.019) compared with those treated with TNF-i., Conclusion: COVID-19 vaccination was not associated with increased rate of flares in patients with RA and PsA. However, a potential increase in disease activity in patients with RA treated with JAK-i and IL-6-i and in patients with PsA treated with IL-12/23-i warrants further investigation., Competing Interests: Competing interests: JMA-G declares consulting/lecture/speaker’s bureau fees from Abbvie, BMS, Galapagos, Lilly, MSD, Pfizer, Roche and UCB. FD-G reports the following conflicts of interest for payment or honoraria for lectures, presentations, speakers’ bureaus for Lilly, Pfizer, UCB and Novartis; payment for expert testimony for Abbvie, Roche and MSD; support for attending meetings for Pfizer; and participation on advisory board for Gilead and receipt of equipment from Abbvie., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Objectives: To analyze the prevalence, incidence, survival and contribution on mortality of major central nervous system (CNS) involvement in systemic lupus erythematosus (SLE)., Methods: Patients fulfilling the SLE 1997 ACR classification criteria from the multicentre, retrospective RELESSER-TRANS (Spanish Society of Rheumatology Lupus Register) were included. Prevalence, incidence and survival rates of major CNS neuropsychiatric (NP)-SLE as a group and the individual NP manifestations cerebrovascular disease (CVD), seizure, psychosis, organic brain syndrome and transverse myelitis were calculated. Furthermore, the contribution of these manifestations on mortality was analysed in Cox regression models adjusted for confounders., Results: A total of 3591 SLE patients were included. Of them, 412 (11.5%) developed a total of 522 major CNS NP-SLE manifestations. 61 patients (12%) with major CNS NP-SLE died. The annual mortality rate for patients with and without ever major CNS NP-SLE was 10.8% vs 3.8%, respectively. Individually, CVD (14%) and organic brain syndrome (15.5%) showed the highest mortality rates. The 10% mortality rate for patients with and without ever major CNS NP-SLE was reached after 12.3 vs 22.8 years, respectively. CVD (9.8 years) and organic brain syndrome (7.1 years) reached the 10% mortality rate earlier than other major CNS NP-SLE manifestations. Major CNS NP-SLE (HR 1.85, 1.29-2.67) and more specifically CVD (HR 2.17, 1.41-3.33) and organic brain syndrome (HR 2.11, 1.19-3.74) accounted as independent prognostic factors for poor survival., Conclusion: The presentation of major CNS NP-SLE during the disease course contributes to a higher mortality, which may differ depending on the individual NP manifestation. CVD and organic brain syndrome are associated with the highest mortality rates., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: One of the most important aims in the management of systemic lupus erythematosus (SLE) is to avoid or delay the accumulation of organ damage. The first five years after diagnosis are crucial for prognosis., Areas Covered: This manuscript reviews available data on organ damage accrual in SLE and early therapeutic intervention as a possible strategy to prevent its long-term accrual., Expert Opinion: Organ damage can be minimized by controlling disease activity and risk of flares, reducing the dose of glucocorticoids, and ensuring a proper therapeutic intervention with an early introduction of the right therapies. The current standard treatment cannot provide clinical remission in all patients with SLE. Therefore, there is a clinical need for introducing new therapeutic strategies able to achieve the main therapeutic objectives. The addition of biologic and other therapeutic agents to the standard of care is effective for controlling disease activity and for preventing severe flares, enabling a reduced use of glucocorticoids, and presumably reducing organ damage progression. Considering its efficacy and safety, early inclusion of biologic agents in the first lines of the treatment algorithm, at least in certain patients, could be considered as an innovative treatment approach to decrease disease burden in SLE patients.

Objective: To assess the efficacy and safety of tocilizumab (TCZ) in Caucasian patients with refractory Takayasu's arteritis (TAK) in clinical practice., Methods: A multicenter study of Caucasian patients with refractory TAK who received TCZ. The outcome variables were remission, glucocorticoid-sparing effect, improvement in imaging techniques, and adverse events. A comparative study between patients who received TCZ as monotherapy (TCZ MONO ) and combined with conventional disease modifying anti-rheumatic drugs (cDMARDs) (TCZ COMBO ) was performed., Results: The study comprised 54 patients (46 women/8 men) with a median [interquartile range (IQR)] age of 42.0 (32.5-50.5) years. TCZ was started after a median (IQR) of 12.0 (3.0-31.5) months since TAK diagnosis. Remission was achieved in 12/54 (22.2%), 19/49 (38.8%), 23/44 (52.3%), and 27/36 (75%) patients at 1, 3, 6, and 12 months, respectively. The prednisone dose was reduced from 30.0 mg/day (12.5-50.0) to 5.0 (0.0-5.6) mg/day at 12 months. An improvement in imaging findings was reported in 28 (73.7%) patients after a median (IQR) of 9.0 (6.0-14.0) months. Twenty-three (42.6%) patients were on TCZ MONO and 31 (57.4%) on TCZ COMBO : MTX ( n  = 28), cyclosporine A ( n  = 2), azathioprine ( n  = 1). Patients on TCZ COMBO were younger [38.0 (27.0-46.0) versus 45.0 (38.0-57.0)] years; difference (diff) [95% confidence interval (CI) = -7.0 (-17.9, -0.56] with a trend to longer TAK duration [21.0 (6.0-38.0) versus 6.0 (1.0-23.0)] months; diff 95% CI = 15 (-8.9, 35.5), and higher c-reactive protein [2.4 (0.7-5.6) versus 1.3 (0.3-3.3)] mg/dl; diff 95% CI = 1.1 (-0.26, 2.99). Despite these differences, similar outcomes were observed in both groups (log rank p  = 0.862). Relevant adverse events were reported in six (11.1%) patients, but only three developed severe events that required TCZ withdrawal., Conclusion: TCZ in monotherapy, or combined with cDMARDs, is effective and safe in patients with refractory TAK of Caucasian origin., Competing Interests: Conflict of interest statement: Disclosures that might be interpreted as constituting of possible conflict(s) of interest for the study: DP-P is supported by a research contract from the Carlos III Health Institute of Spain (Rio Hortega program, ref. CM20/00006) and has received research support from UCB Pharma, Roche, Sanofi, Pfizer, AbbVie, and Lilly. MAG-G received grants/research supports from Abbvie, MSD, Jansen, and Roche and had consultation fees/participation in company sponsored speaker’s bureau from Abbvie, Pfizer, Roche, Sanofi, Lilly, Celgene, and MSD. RB received grants/research supports from Abbvie, MSD, and Roche, and had consultation fees/participation in company sponsored speaker’s bureau from Abbvie, Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma, and MSD. The remaining authors declare they do not have conflict of interest., (© The Author(s), 2021.)

Introduction: Antiphospholipid antibodies (aPL) have been associated with organ damage and certain features in systemic lupus erythematosus(SLE) patients. Our aim was to investigate the differences between SLE patients according to the presence of aPL and/or clinical antiphospholipid syndrome (APS)., Materials and Methods: Patients from the RELESSER-T registry were included. RELESSER-T is a Spanish multicenter, hospital-based, retrospective, SLE registry., Results: We included 2398 SLE patients, 1372 of whom were positive for aPL. Overall 1026 patients were classified as SLE, 555 as SLE-APS and817 as SLE-aPL. Regarding cardiovascular risk factors, SLE-APS patients had higher rates of hypertension, dyslipidemia and diabetes than those with SLE-aPL and SLE ( p  < 0.001). SLE-APS patients showed higher rates of neuropsychiatric, cardiac, pulmonary, renal and ophthalmological manifestations than the other groups ( p  < 0.001). SLE-APS patients presented greater damage accrual with higher SLICC values (1.9 ± 2.2 in SLE-APS, 0.9 ± 1.4 in SLE-aPL and 1.1 ± 1.6 in SLE, p  < 0.001) and more severe disease as defined by the Katz index (3 ± 1.8 in SLE-APS, 2.7 ± 1.7 in SLE-aPL and 2.6 ± 1.6 in SLE, p  < 0.001). SLE-APS patients showed higher mortality rates ( p  < 0.001)., Conclusions: SLE-APS patients exhibited more severe clinical profiles with higher frequencies of major organ involvement, greater damage accrual and higher mortality than SLE-aPL and SLE patients.

Management of systemic autoimmune diseases is challenging for physicians in their clinical practice. Although not common, they affect thousands of patients in Spain. The family doctor faces patients with symptoms and non-specific cutaneous, mucous, joint, vascular signs or abnormal laboratory findings at the start of the disease process and has to determine when to refer patients to the specialist. To aid in disease detection and better referral, the Spanish Society of Rheumatology and the Spanish Society of Family Medicine has created a group of experts who selected 26 symptoms, key signs and abnormal laboratory findings which were organized by organ and apparatus. Family doctors and rheumatologists with an interest in autoimmune systemic diseases were selected and formed mixed groups of two that then elaborated algorithms for diagnostic guidelines and referral. The algorithms were then reviewed, homogenized and adapted to the algorithm format and application for cell phone (apps) download. The result is the current Referral document of systemic autoimmune diseases for the family doctor in paper format and app (download). It contains easy-to-use algorithms using data from anamnesis, physical examination and laboratory results usually available to primary care, that help diagnose and refer patients to rheumatology or other specialties if needed., (Copyright © 2019 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Objectives: The main goal was to assess the reasons for antiretroviral therapy (ART) change in patients with HIV in a hospital setting in routine clinical practice. The economic impact of ART modification was also analysed., Methods: Patients with HIV who changed their ART between 24 November and 24 December 2014 were registered. Length of initial therapy, type of ART before and after therapy modification, and reasons for the ART change were analysed. To assess the economic impact, antiretroviral drug costs at the time of the study were recorded., Results: Of a cohort of 3850 patients with HIV, 1976 attended for pharmaceutical care consultation at Hospital Universitario La Paz during the study period. Ninety-two patients (4.7%) had their ART modified. The median length of the previous therapy was 26 months (range 1-144). The most common initial therapy regimen was 2 nucleoside reverse transcriptase inhibitors (NRTI)+1 non-nucleoside reverse transcriptase inhibitor (NNRTI) (29.4%), and the most common one after modification was 2 NRTI+1 integrase strand transfer inhibitor (INSTI) (40.2%). Forty-three modifications were made because of toxicity and adverse effects (46.7%), 25 because of therapy simplification (27.2%), 16 because of treatment failure (17.4%), and 8 because of drug-drug interactions (8.7%). ART costs increased by a mean of €14 (SD €216; range -€528 to +€831) per month per patient after therapy modification at the time of study., Conclusions: Toxicity and adverse effects were the most common reason for ART alteration in patients with HIV in routine clinical practice in a hospital setting. Better knowledge about factors that motivate these changes may contribute to decreased toxicity and increased treatment success. ART modification had a variable but not very substantial economic impact., Competing Interests: Competing interests: None declared.

This article estimates the frequency of cardiovascular (CV) events that occurred after diagnosis in a large Spanish cohort of patients with systemic lupus erythematosus (SLE) and investigates the main risk factors for atherosclerosis. RELESSER is a nationwide multicenter, hospital-based registry of SLE patients. This is a cross-sectional study. Demographic and clinical variables, the presence of traditional risk factors, and CV events were collected. A CV event was defined as a myocardial infarction, angina, stroke, and/or peripheral artery disease. Multiple logistic regression analysis was performed to investigate the possible risk factors for atherosclerosis. From 2011 to 2012, 3658 SLE patients were enrolled. Of these, 374 (10.9%) patients suffered at least a CV event. In 269 (7.4%) patients, the CV events occurred after SLE diagnosis (86.2% women, median [interquartile range] age 54.9 years [43.2-66.1], and SLE duration of 212.0 months [120.8-289.0]). Strokes (5.7%) were the most frequent CV event, followed by ischemic heart disease (3.8%) and peripheral artery disease (2.2%). Multivariate analysis identified age (odds ratio [95% confidence interval], 1.03 [1.02-1.04]), hypertension (1.71 [1.20-2.44]), smoking (1.48 [1.06-2.07]), diabetes (2.2 [1.32-3.74]), dyslipidemia (2.18 [1.54-3.09]), neurolupus (2.42 [1.56-3.75]), valvulopathy (2.44 [1.34-4.26]), serositis (1.54 [1.09-2.18]), antiphospholipid antibodies (1.57 [1.13-2.17]), low complement (1.81 [1.12-2.93]), and azathioprine (1.47 [1.04-2.07]) as risk factors for CV events. We have confirmed that SLE patients suffer a high prevalence of premature CV disease. Both traditional and nontraditional risk factors contribute to this higher prevalence. Although it needs to be verified with future studies, our study also shows-for the first time-an association between diabetes and CV events in SLE patients.

We herein report a patient who came to the hospital because of a polyarticular joint pain, fever and cutaneous lesions. She had silicone implants in her buttocks, a surgery performed 3 years before. We made a biopsy of the skin of the buttocks (facticial panniculitis due to silicone) and of the pretibial surface of the inferior extremities (erythema nodosum). A chest X- ray and a CT scan revealed bilateral hiliar lymphadenopathy, and a transbronquial biopsy showed granulomatous inflammation. She had a good response to rest and anti-inflammatory drugs, so the removal of the silicone implants has not been necessary yet., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)