The susceptibility of patients with rheumatic diseases and the risks or benefits of immunosuppressive therapies for COVID-19 are unknown.
We performed a retrospective study with patients under ...follow-up in rheumatology departments from seven hospitals in Spain. We matched updated databases of rheumatology patients with severe acute respiratory syndrome coronavirus 2-positive PCR tests performed in the hospital to the same reference populations. Rates of PCR+ confirmed COVID-19 were compared among groups.
Patients with chronic inflammatory diseases had 1.32-fold higher prevalence of hospital PCR+ COVID-19 than the reference population (0.76% vs 0.58%). Patients with systemic autoimmune or immune-mediated disease (AI/IMID) showed a significant increase, whereas patients with inflammatory arthritis (IA) or systemic lupus erythematosus did not. COVID-19 cases in some but not all diagnostic groups had older ages than cases in the reference population. Patients with IA on targeted-synthetic or biological disease-modifying antirheumatic drugs (DMARDs), but not those on conventional-synthetic DMARDs, had a greater prevalence despite a similar age distribution.
Patients with AI/IMID show a variable risk of hospital-diagnosed COVID-19. Interplay of ageing, therapies and disease-specific factors seem to contribute. These data provide a basis to improve preventive recommendations to rheumatic patients and to analyse the specific factors involved in COVID-19 susceptibility.
The purpose of this study was to assess the prevalence, associated factors, and impact on mortality of primary respiratory disease in a large systemic lupus erythematosus (SLE) retrospective cohort.
...All adult patients in the RELESSER-TRANS (Registry of Systemic Lupus Erythematosus Patients of the Spanish Society of Rheumatology SER, cross-sectional phase) registry were retrospectively investigated for the presence of primary pleuropulmonary manifestations.
In total 3215 patients were included. At least one pleuropulmonary manifestation was present in 31% of patients. The most common manifestation was pleural disease (21%), followed by lupus pneumonitis (3.6%), pulmonary thromboembolism (2.9%), primary pulmonary hypertension (2.4%), diffuse interstitial lung disease (2%), alveolar hemorrhage (0.8%), and shrinking lung syndrome (0.8%). In the multivariable analysis, the variables associated with the development of pleuropulmonary manifestation were older age at disease onset (odds ratio (OR) 1.03, 95% confidence interval (CI) 1.02-1.04), higher SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) scores (OR 1.03, 95% CI 1.00-1.07), the presence of Raynaud's phenomenon (OR 1.41, 95% CI 1.09-1.84), secondary antiphospholipid syndrome (OR 2.20, 95% CI 1.63-2.97), and the previous or concomitant occurrence of severe lupus nephritis, (OR 1.48, 95% CI 1.12-1.95) neuropsychiatric manifestations (OR 1.49, 95% CI 1.11-2.02), non-ischemic cardiac disease (OR 2.91, 95% CI 1.90-4.15), vasculitis (OR 1.81, 95% CI 1.25-2.62), hematological manifestations (OR 1.31, 95% CI 1.00-1.71), and gastrointestinal manifestations, excluding hepatitis (OR 2.05, 95% CI 1.14-3.66). Anti-RNP positivity had a clear tendency to significance (OR 1.32, 95% CI 1.00-1.75; P = 0.054). The development of pleuropulmonary manifestations independently contributes to a diminished survival (hazard ratio of 3.13). However, not all complications will influence the prognosis in the same way. Whereas the occurrence of pleural disease or pulmonary thromboembolism has a minimal impact on the survival of these patients, the remaining manifestations have a major impact on mortality.
Except for pleural disease, the remaining respiratory manifestations are very uncommon in SLE (<4%). Pleuropulmonary manifestations independently contributed to a decreased survival in these patients.
The complement system (CS) includes more than 50 proteins and its main function is to recognize and protect against foreign or damaged molecular components. Other homeostatic functions of CS are the ...elimination of apoptotic debris, neurological development, and the control of adaptive immune responses. Pathological activation plays prominent roles in the pathogenesis of most autoimmune diseases such as systemic lupus erythematosus, antiphospholipid syndrome, rheumatoid arthritis, dermatomyositis, and ANCA-associated vasculitis. In this review, we will review the main rheumatologic autoimmune processes in which complement plays a pathogenic role and its potential relevance as a therapeutic target.
Transforming growth factor-beta (TGF-β) is a cytokine with pleiotropic functions in hematopoiesis, angiogenesis, cell proliferation, differentiation, migration and apoptosis. Although its role in ...rheumatoid arthritis is not well defined, TGF-β activation leads to functional immunomodulatory effects according to environmental conditions. The function of TGF-β in the development of arthritis in murine models has been extensively studied with controversial results. Recent findings point to a non-relevant role for TGF-β in a mice model of collagen-induced arthritis. The study of TGF-β on T-cell responses has shown controversial results as an inhibitor or promoter of the inflammatory response. This paper presents a review of the role of TGF-β in animal models of arthritis.
To analyze the trend of orthopedic surgery (OS) rates on patients with rheumatoid arthritis (RA).
Retrospective observational study based on information provided by the Spanish National System of ...Hospital Data Surveillance. All hospitalizations of patients with RA for orthopedic surgery total hip arthroplasty (THA), total knee arthroplasty (TKA), arthrodesis, and upper limb arthroplasty (ULA) during 1999-2015 were analyzed. The age-adjusted rate was calculated. Generalized linear models were used for trend analysis.
There were 21,088 OS in patients over 20 years of age (77.9% women). OS rate adjusted by age was 754.63/100,000 RA patients/year (women 707.4, men 861.1). Neither an increasing nor a decreasing trend was noted for the total OS. However, trend and age interacted, so in the age ranges 20-40 years and 40-60 years, an annual reduction of 2.69% and 2.97%, respectively, was noted. In the age ranges over 80 years and 60-80 years, we noted an annual increase of 5.40% and 1.09%, respectively. The average age at time of OS increased 5.5 years during the period analyzed. For specific surgeries, a global annual reduction was noted in rates for arthrodesis. In THA, there was an annual reduction in patients under 80 years. In TKA and ULA, there was an annual reduction in patients under 60 years.
Although the overall OS rate has not changed, there is a decrease in the rate of arthrodesis at all ages, THA in patients under 80 years of age, as well as TKA and ULA in patients under 60 years of age.
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.
To provide an overview on the current use of belimumab (BLM) in SLE patients in clinical practice and to examine its efficacy in terms of standardized outcomes, drug survival, as well as patient and ...safety profiles.
A longitudinal retrospective multicentre cohort including SLE patients treated with BLM at 18 Spanish centers. Data was collected upon initiation of BLM, at 6 and 12 months after initiation, and at the last recorded visit. Changes in SLEDAI-2K, the proportion of patients who achieved LLDAS and DORIS 2021, and number of flares were compared between visits. Changes in damage, glucocorticoids use and employment status pre-BLM and post-BLM were also assessed.
A total of 324 patients were included with a mean follow-up of 3.8 (±2.7) years. LLDAS was attained by 45.8%, 62% and 71% of patients, and DORIS by 24%, 36.2% and 52.5% on successive visits, respectively. Twenty-seven-point two percent of patients were in DORIS ≥ 50% of the visits and a 46% in LLDAS-50. Flares and number of flares were significantly lower one year after treatment with BLM and no changes in damage accrual were observed. Mean (±SD) prednisone dose was significantly reduced over time, with 70 (24%) patients discontinuing GC.
Our study not only demonstrates belimumab´s efficacy in attaining treat-to-target goals in SLE patients, but also confirms its GC-sparing effect, and its prevention of flares and organ damage accrual.
Objectives
A survey conducted by the Spanish Lupus Federation (FELUPUS) shows the results on perceptions and experiences of the people who live with lupus in Spain. The information was gathered ...anonymously from May 21
st
to June 30
th
, 2020. The aim of the study was to monitor the impact of the disease on quality of life, as well as to measure the impact of organ damage in lupus patients.
Methods
A national survey was conducted among people with lupus living in Spain who belong to the Spanish Lupus Patient Association (FELUPUS). Online interviews of approximately 25 min were completed. The information was gathered anonymously from May 21
st
to June 30
th
, 2020.
Results
One thousand two hundred sixty-three interviews were completed. 92% had a diagnosis of Systemic Lupus Erythematosus (SLE) and 8% of Cutaneous Lupus Erythematosus (CLE); 95% of the patients surveyed were female. Most of the patients claimed they stay up late, exercising and work/study were the most limited actions due to the disease. 73% of patients considered that there was little knowledge of the disease by society and at the time of diagnosis, the patient’s level of knowledge about lupus was low in 92% of them. Regarding organ damage, many patients did not understand the concept of chronicity and irreversibility of the term, relating it erroneously to acute symptoms like fatigue (38%), joint pain (47%) and even to the presence of cutaneous symptoms such as the presence of oral ulcers (17%).
Conclusions
The survey highlighted the need for disease awareness campaigns, greater involvement of healthcare professionals and the need to provide more information to lupus patients from the time of diagnosis. Nationally and to our knowledge, this is the survey with the largest number of participants (
N
= 1263) conducted in patients with lupus.
Key Points
•
A national survey was conducted among people with lupus living in Spain and belonging to patient associations in Spain (FELUPUS).
•
Nationally and to our knowledge, this is the survey with the largest number of participants (N = 1263) conducted in patients with lupus.
•
Most of the patients claimed they stay up late, exercising and work/study were the most limited actions due to the disease.
•
73% of patients considered that there is little knowledge of the disease by society and at the time of diagnosis, the patient’s level of knowledge about lupus was low in 92% of them.
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 ± 12.7 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.
Obstetric complications are more common in women with systemic lupus erythematosus (SLE) than in the general population.
To assess pregnancy outcomes in women with SLE from the RELESSER cohort after ...12 years of follow-up.
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.
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.
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.
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