Objectives To evaluate factors associated with COVID-19 severity outcomes in patients with systemic lupus erythematosus (SLE). Methods This was a cross-sectional analysis of baseline data of a prospective, multi-stage cohort study—“The ReumaCoV Brazil”—designed to monitor patients with immune-mediated rheumatologic disease (IMRD) during the SARS-CoV-2 pandemic. SLE adult patients with COVID-19 were compared with those without COVID-19. SLE activity was evaluated by the patient global assessment (PGA) and SLE Disease Activity Index 2000 (SLEDAI-2K). Results 604 SLE patients were included, 317 (52.4%) with COVID-19 and 287 (47.6%) in the control group. SLE COVID-19 patients reported a lower frequency of social isolation and worked more frequently as health professionals. There was no difference in the mean SLEDAI-2K score between groups in the post–COVID-19 period (5.8 [8.6] vs. 4.5 [8.0]; p = 0.190). However, infected patients reported increased SLE activity according to the Patient Global Assessment (PGA) during this period (2.9 [2.9] vs. 2.3 [2.6]; p = 0.031. Arterial hypertension (OR 2.48 [CI 95% 1.04–5.91], p = 0.041), cyclophosphamide (OR 14.32 [CI 95% 2.12–96.77], p = 0.006), dyspnea (OR: 7.10 [CI 95% 3.10–16.23], p < 0.001) and discontinuation of SLE treatment medication during infection (5.38 [CI 95% 1.97–15.48], p = 0.002), were independently associated with a higher chance of hospitalization related to COVID-19. Patients who received telemedicine support presented a 67% lower chance of hospitalization (OR 0.33 [CI 95% 0.12–0.88], p = 0.02). Conclusion Hypertension and cyclophosphamide were associated with a severe outcome, and telemedicine can be a useful tool for SLE patients with COVID-19.
BackgroundInterferon-lambda 1 (IFNl1), also known as Interleukin-29, belongs to the family of type III interferons and is produced by human peripheral blood mononuclear cells (PBMC) and dendritic cells. It was already described antiviral, anti-proliferative and antitumor effects of IFNl1, but immune-regulatory function is still gradually been elucidated. In human T cells, this cytokine was able to inhibit Th2 response by diminishing secretion of IL-4, IL-5 and, mainly, IL-13 but its real role in pathophysiology of human diseases is still unclear.ObjectivesTo evaluate serum levels of IFNl1 in systemic sclerosis (SSc) patients and healthy controls and its association with Th1 and Th2 cytokines.MethodsSerum samples were obtained from 52 SSc patients (49 women, 3 men) with a mean age of 44.8 years (range 19–79 yrs) and 53 sex and age matched healthy controls. ELISAs for serum levels of IFNl1, IFNg, TNFa, IL-13, IL-2, IL-4, IL-6 and IL-10 were performed with commercially available sandwich ELISA kits, according to the manufacturer's instructions.ResultsIFNl1 levels in patients with SSc were significantly higher than those in healthy individuals (24.82±8.78 and 11.04±3.04 pg/ml, respectively; p<0.0001). Also, SSc patients had higher IFNg levels than controls (34.11±8.11 and 10.73±2.77 pg/ml, respectively; p<0.0001). Furthermore, we found a positive correlation between IL-29 and IFNg levels in SSc patients (p=0.0103, r=0.3526). IL-2, IL-4, IL-6, IL-10, IL-13 and TNFa were not detected in most of the patients and normal controls serum. We found that patients with myositis had higher IFNg levels than those without muscle involvement (p=0.0483) but no significant association was found between IL-29 levels and clinical manifestations.ConclusionsIL-29 levels are increased in SSc and are positively correlated with IFNg levels, a Th1 cytokine. Because of its strong inhibitory effect on Th2 pathway demonstrated by previous studies, at this point, we can only speculate on the potential role of IL-29 as an anti-fibrotic cytokine and additional longitudinal studies are needed to evaluate this concernReferencesJordan WJ, Eskdale J, Srinivas S, Pekarek V, Kelner D, Rodia M, Gallagher G.Human interferon lambda-1 (IFN-lambda1/IL-29) modulates the Th1/Th2 response. Genes Immun. 2007 Apr;8(3):254-61.Srinivas S, Dai J, Eskdale J, Gallagher GE, Megjugorac NJ, Gallagher G. Interferon-lambda1 (interleukin-29) preferentially down-regulates interleukin-13 over other T helper type 2 cytokine responses in vitro. Immunology. 2008 Dec;125(4):492-502.Wu Q, Yang Q, Lourenco E, Sun H, Zhang Y. Interferon-lambda1 induces peripheral blood mononuclear cell-derived chemokines secretion in patients with systemic lupus erythematosus: its correlation with disease activity. Arthritis Res Ther. 2011 Jun 16;13(3):R88.Disclosure of InterestNone declared
BackgroundSystemic lupus erythematosus (SLE) is an autoimmune inflammatory disease with a wide spectrum of clinical manifestations that affect about a million people around the world1. The American College of Rheumatology (ACR) published in 1982 and revised in 19972 the most widely classification criteria used today. The SLICC (The Systemic Lupus International Collaborating Clinics) is a group dedicated to the research of SLE, which in 2012 issued a list of 17 criteria whose internal validation resulted in fewer errors ratings and higher sensitivity, even though it had lower specificity compared to ACR norms3.ObjectivesTo validate the SLICC's SLE criteria when applied to the Brazilian population.MethodsRetrospective cross-sectional study based on medical records analysis of patients attending the SLE, rheumatoid arthritis (RA) and systemic sclerosis (SE) clinic at the Hospital das Clínicas (HC) - Federal University of Pernambuco (UFPE). The previous diagnosis of overlap syndrome was an exclusion condition.ResultsAfter a medical chart review of 287 patients (89 with SLE, 99 with RA and 99 with SE), 85 from the SLE set had a diagnosis defined by the ACR criteria, one patient was probable SLE (three criteria of the ACR), two were possible SLE (two criteria of the ACR) and another one had only a positive ANA. When applied SLICC, these four patients met the standards for diagnosis by SLICC. However, from the 89 SLE patients, three did not gathered the necessary criteria. In the SE group, one of the patients had both standards for SLE and three others had a SLICC diagnosis. All of these three would have a probable SLE diagnosis by ACR requirements. Among the 99 patients with RA, none had sufficient criteria for a SLE diagnosis. The criteria accuracy took into account the characteristics of the service, since many patients had no direct coombs dosage and antibodies such as anti-DNA, anti-Sm and anti-phospholipid. Therefore, the ACR showed 96% sensitivity and 99% specificity and the SLICC 96% and 97%, respectively. When compared, the requirements reached a high level of concurrence with a 0.887 Kappa.ConclusionsThe SLICC exhibited sensitivity and specificity similar to the ACR even with the adversities faced in the service, inherent to many hospitals in developing countries. Patients with uncertain diagnosis of SLE will benefit from these new criteria by SLICC. However, one must be careful with the false positives, when the physicians' clinical experience will be fundamental to the differential SLE diagnosis.ReferencesDanchenko N, Satia JA, Anthony MS. Epidemiology of systemic lupus erythematosus: a comparison of worldwide disease burden. Lupus 2006; 15:308 - 18Tan EM, Cohen AS, Fries FJ, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25:1271-7Petri M, Madger L. Classification criteria for systemic lupus erythematosus: a review. Lupus 2004; 13:829-37Disclosure of InterestNone declared
Background:The role of chronic use of hydroxychloroquine (HCQ) in rheumatic disease (RD) patients during the SARS-CoV-2 pandemic is still subject of discussion.Objectives:To compare the occurrence of COVID-19 and its outcomes between RD patients on HCQ use with individuals from the same household not taking the drug during community viral transmission in an observational prospective multicenter study in Brazil.Methods:Participants were enrolled and monitored through 24-week (From March 29th to Sep 30th, 2020) regularly scheduled phone calls performed by trained medical professionals. Epidemiological and demographic data, as well as RD disease activity status and current treatment data, specific information about COVID-19, hospitalization, need for intensive care, and death was recorded in both groups and stored in the Research Electronic Data Capture (REDCap) database. COVID-19 was defined according to the Brazilian Ministry of Health (BMH) criteria. The statistical analysis was performed using IBM-SPSS v.20.0 software. Group comparisons were made using the Man-Whitney, Chi-Square and Fisher Exact Test, as well as multivariate regression models adjusted to confounders. Survival curves were performed using Kaplan-Meier analysis.Results:A total of 10,427 participants mean age (SD) of 44.04 (14.98) years were enrolled, including 6004 (57.6%) rheumatic disease patients, of whom 70.8% had systemic lupus erythematosus (SLE), 6.7% rheumatoid arthritis (RA), 4% primary Sjögren’s syndrome (pSS), 1.8% mixed connective tissue disease (DMTC), 1% systemic sclerosis (SSc) and others (15.9), including overlap syndromes. In total, 1,132 (10.8%) participants fulfilled criteria for COVID-19, being 6.7% RD patients and 4.1% controls (p=0.002). A recent influenza vaccination had a protective role (p<0.001). Moderate and severe COVID-19 included the need for hospitalization, intensive care, mechanical ventilation or death. Infection severity was not different between groups (p=0.391) (Table 1). After adjustments for multiple confounders, the main risk factors significantly associated with COVID-19 were higher education level (OR=1.29 95%CI 1.05-1.59), being healthcare professionals (OR=1.91; 95%CI 1.45-2.53), presence of two comorbidities (OR=1.31; 95%CI 1.01-1.66) and three or more comorbidities associated (OR=1.69; 95%CI 1.23-2.32). Interestingly, age >=65 years (OR=0.20; 95%CI 0.11-0.34) was negatively associated. Regarding RD, the risk factors associated with COVID-19 diagnosys were SLE (OR= 2.37; 95%CI 1.92-293), SSc (OR=2.25; 95%CI 1.05-4.83) and rituximab use (OR=1.92; 95%CI 1.13-3.26). In addition, age >=65 years (OR=5.47; 95%CI 1.7-19.4) and heart disease (OR=2.60; 95%CI 1.06-6.38) were associated with hospitalization. Seven female RD patients died, six with SLE and one with pSS, and the presence of two or more comorbidities were associated with higher mortality rate.Conclusion:Chronic HCQ use did not prevent COVID-19 in RD compared to their household cohabitants. Health care profession, presence of comorbidities LES, SSc and rituximab were identified as main risk factors for COVID-19 and aging and heart disease as higher risk for hospitalization. Our data suggest these outcomes could be considered to manage them in clinical practice.Table 1.Frequency and severity of COVID-19 in patients with rheumatic diseases on chronic use of hydroxychloroquine compared to their household controlsCOVID-19 outcomesTotal(%)GroupsPPatients(%)Controls (%)DiagnosisNo9256 (89.1)5300 (88.3)3956 (90.2)0.002Yes1132 (10.9)704 (11.7)428 (9.8)SeverityMild1059 (93.6)662 (94.0)397 (92.8)0.391Moderate52 (4.6)32 (4.5)20 (4.7)Severe21 (1.9)10 (1.4)11 (2.6)HCQ: hydroxychloroquine.Moderate and severe COVID-19 included the need for any of the following: hospitalization, intensive care, mechanical ventilation or death.Acknowledgements:To the Brazilian Society of Rheumatology for technical support and rapid nationwide mobilization.To all the 395 interviewers (medical students and physicians) who collaborated in the study and the participantsTo CNPq (Number 403442/2020-6)Disclosure of Interests:None declared
BackgroundGout is considered an autoinflammatory disease characterized by activation of innate immunity. The presence of uric acid crystals causes oligomerization and dysfunctional activity of NPRL3 inflammasome macromolecules, resulting in hyperactivity of caspase-1. This process causes increased secretion of inflammatory cytokines such as IL-1β and IL-18. These cytokines, in turn, trigger a cascade of proinflammatory mediators, leading ultimately to endothelial activation and leukocyte recruitment. The main cytokines with secondary involvement in this process are IL-8 (neutrophil recruitment and activation), IL-6 (amplification of the inflammatory process, possible contribution to bone damage), TNFα (proinflammatory activation, maturation and increased monocyte to macrophage transformation). The association between serum cytokines levels and clinical manifestations of the disease, however, is not yet well understood.ObjectivesEvaluated the serum profile of proinflammatory cytokines in gout (IL-1β, IL-6, IL-8, IL-17A, IL-18, IL-22 and IL-23) and described their relationship with clinical and laboratory data in a group of patients with the disorderMethodsThis is a cross-sectional, observational study of 39 male patients with gout (GG), assessing the following variables: age, disease duration, body mass index (BMI), presence or not of comorbidities such as diabetes mellitus (DM), arterial hypertension (AH), dyslipidemia (DLD), and the presence of tophi, deformities and arthritis. Laboratory data on erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and uric acid were also analyzed. Levels of IL-1β, IL-6, IL-8, IL-17A, IL-18, IL-22 and IL-23 were measured by ELISA, following the supplier's recommendations. For the purposes of comparison, 34 males with no previous history of arthritis were also included in the study (CG).ResultsThe average age in the GG was 58.2 (±1.6) years and 54.3 (±1.8) years (p=0.102) in the CG. Seventeen participants (43%) exhibited active arthritis on evaluation. Levels of IL-18 were significantly higher in patients in relation to the CG (p=0.0013). No statistically significant differences were found between the GG and CG for the other measured cytokines. There was moderate correlation between IL-18 and ESR (R=0.43, p=0.0073), PCR (R=0.47, p=0.0025) and serum levels of IL-6 (R=0.36, p=0.023). No correlation was recorded between the cytokines analyzed and uric acid, age, time since diagnosis or the presence of comorbidities. An association was observed between serum levels of IL-6 and the presence of tophi (p=0.005) and deformities (p=0.0008), as well as a correlation between this cytokine and ESR (R=0.41, p=0.011) and CRP (R=0.48, p=0.02).ConclusionsIL-18 was correlated with inflammatory activity in gout, as well as IL-6 levels, while IL-6 was associated with clinical and laboratory activity, the presence of tophi and deformities, and may be a prognostic marker or influence the development of joint damage this pathology.Disclosure of InterestNone declared
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