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Objectives: To compare the correlations of histological class inferences based on clinical manifestations and laboratory tests between rheumatologists and nephrologists, to determine the associations of clinical and laboratory data with histological classes and to develop an instrument that can assist histological class identification in lupus nephritis (LN)., Methods: Retrospective study based on medical records of 80 systemic lupus erythematosus patients (SLICC criteria classification, 2012) who underwent kidney biopsy between 2010 and 2017. Two rheumatologists and two nephrologists received clinical and laboratory data and answered questions regarding which histological class was expected on kidney biopsy. Kappa (K) coefficient was used to assess agreement between evaluators. A decision tree was constructed using the chi-square interaction detector and logistic regression was performed for the development of the proliferative histological class predictor instrument ., Results: The mean age and disease duration were 33 ± 10.3 years and 11.5 ± 6.7 years, respectively. The level of agreement between the evaluators and kidney biopsy was poor (global K 0.364 ± 0.029; p < .001). Analyzing clinical and laboratory variables as predictors of proliferative histological class, patients with abnormal urinary sediment and positive anti-dsDNA antibodies presented 13.96 and 4.96 times higher risks of presenting class III or IV, respectively ( p < 0.001). Our instrument has a sensitivity of 87.8% and specificity of 80%, using abnormal urinary sediment, anti-dsDNA antibodies, and serum creatinine as variables., Conclusions: Rheumatologists and nephrologists with experience in treating LN generated evaluations that correlated weakly with kidney biopsy. When kidney biopsy is unavailable or is contraindicated for medical reasons, instruments based on clinical and laboratory predictors may be helpful.

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.

Personalized medicine (PM) aims individualized approach to prevention, diagnosis, and treatment. Precision Medicine applies the paradigm of PM by defining groups of individuals with akin characteristics. Often the two terms have been used interchangeably. The quest for PM has been advancing for centuries as traditional nosology classification defines groups of clinical conditions with relatively similar prognoses and treatment options. However, any individual is characterized by a unique set of multiple characteristics and therefore the achievement of PM implies the determination of myriad demographic, epidemiological, clinical, laboratory, and imaging parameters. The accelerated identification of numerous biological variables associated with diverse health conditions contributes to the fulfillment of one of the pre-requisites for PM. The advent of multiplex analytical platforms contributes to the determination of thousands of biological parameters using minute amounts of serum or other biological matrixes. Finally, big data analysis and machine learning contribute to the processing and integration of the multiplexed data at the individual level, allowing for the personalized definition of susceptibility, diagnosis, prognosis, prevention, and treatment. Autoantibodies are traditional biomarkers for autoimmune diseases and can contribute to PM in many aspects, including identification of individuals at risk, early diagnosis, disease sub-phenotyping, definition of prognosis, and treatment, as well as monitoring disease activity. Herein we address how autoantibodies can promote PM in autoimmune diseases using the examples of systemic lupus erythematosus, antiphospholipid syndrome, rheumatoid arthritis, Sjögren syndrome, systemic sclerosis, idiopathic inflammatory myopathies, autoimmune hepatitis, primary biliary cholangitis, and autoimmune neurologic diseases., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: To determine characteristics associated with more severe outcomes in a global registry of people with systemic lupus erythematosus (SLE) and COVID-19., Methods: People with SLE and COVID-19 reported in the COVID-19 Global Rheumatology Alliance registry from March 2020 to June 2021 were included. The ordinal outcome was defined as: (1) not hospitalised, (2) hospitalised with no oxygenation, (3) hospitalised with any ventilation or oxygenation and (4) death. A multivariable ordinal logistic regression model was constructed to assess the relationship between COVID-19 severity and demographic characteristics, comorbidities, medications and disease activity., Results: A total of 1606 people with SLE were included. In the multivariable model, older age (OR 1.03, 95% CI 1.02 to 1.04), male sex (1.50, 1.01 to 2.23), prednisone dose (1-5 mg/day 1.86, 1.20 to 2.66, 6-9 mg/day 2.47, 1.24 to 4.86 and ≥10 mg/day 1.95, 1.27 to 2.99), no current treatment (1.80, 1.17 to 2.75), comorbidities (eg, kidney disease 3.51, 2.42 to 5.09, cardiovascular disease/hypertension 1.69, 1.25 to 2.29) and moderate or high SLE disease activity (vs remission; 1.61, 1.02 to 2.54 and 3.94, 2.11 to 7.34, respectively) were associated with more severe outcomes. In age-adjusted and sex-adjusted models, mycophenolate, rituximab and cyclophosphamide were associated with worse outcomes compared with hydroxychloroquine; outcomes were more favourable with methotrexate and belimumab., Conclusions: More severe COVID-19 outcomes in individuals with SLE are largely driven by demographic factors, comorbidities and untreated or active SLE. Patients using glucocorticoids also experienced more severe outcomes., Competing Interests: Competing interests: MFU-G has received research grants from Pfizer and Janssen, not related to this manuscript. AD-G is supported by the Rheumatology Research Foundation (Scientist Development Award) and the Centers for Disease Control and Prevention. CR-S has received research grants from Janssen, not related to this manuscript. AEC has received consulting fees from AstraZeneca, BMS and GSK, all unrelated to this manuscript. LW has received consulting fees and speaker’s honoraria from Aurinia Pharma unrelated to this manuscript. GJP-E reports no competing interests related to this work. Outside of this work, he reports personal consulting and/or speaking fees from Pfizer, GSK, Janssen and Sanofi (all

Background: Acute transverse myelitis (ATM) is an infrequent but severe complication of systemic lupus erythematosus (SLE). The purpose of study was to describe clinical features and prognostic factors of patients with SLE-related ATM., Methods: In this medical records review study, data were collected from 60 patients from 16 centers seen between 1996 and 2017 who met diagnostic criteria for SLE and myelitis as defined by the American College of Rheumatology/Systemic International Collaborating Clinics and the Working Group of the Transverse Myelitis Consortium, respectively. Objective neurological impairment was measured with American Spinal Injury Association Impairment Scale (AIS) and European Database for Multiple Sclerosis Grade Scale (EGS)., Results: Among patients included, 95% (n = 57) were female, and the average age was 31.6 ± 9.6 years. Myelitis developed after diagnosis of SLE in 60% (n = 36). Symmetrical paraparesis with hypoesthesia, flaccidity, sphincter dysfunction, AIS = A/B, and EGS ≥ 8 was the most common presentation. Intravenous methylprednisolone was used in 95% (n = 57), and 78.3% (n = 47) received intravenous cyclophosphamide. Sensory/motor recovery at 6 months was observed in 75% (42 of 56), but only in 16.1% (9 of 56) was complete. Hypoglycorrhachia and EGS ≥ 7 in the nadir were associated with an unfavorable neurological outcome at 6 months (p < 0.05). A relapse rate during follow-up was observed in 30.4% (17 of 56). Hypoglycorrhachia and hypocomplementemia seem to be protective factors for relapse. Intravenous cyclophosphamide was associated with time delay to relapse., Conclusions: Systemic lupus erythematosus-related ATM may occur at any time of SLE course, leading to significant disability despite treatment. Relapses are infrequent and intravenous cyclophosphamide seems to delay it. Hypoglycorrhachia, hypocomplementemia, and EGS at nadir are the most important prognostic factors., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Hydroxychloroquine and chloroquine, also known as antimalarial drugs, are widely used in the treatment of rheumatic diseases and have recently become the focus of attention because of the ongoing COVID-19 pandemic. Rheumatologists have been using antimalarials to manage patients with chronic immune-mediated inflammatory rheumatic diseases for decades. It is an appropriate time to review their immunomodulatory and anti-inflammatory mechanisms impact on disease activity and survival of systemic lupus erythematosus patient, including antiplatelet effect, metabolic and lipid benefits. We also discuss possible adverse effects, adding a practical and comprehensive approach to monitoring rheumatic patients during treatment with these drugs.

Objective: To determine the incidence of positive CMV antigenemia (CMV-Ag) in patients with autoimmune rheumatic diseases (AIRD) and to describe the outcomes of these patients., Methods: From January 2011 to December 2014, a total of 443 patients with AIRD were enrolled in this retrospective analysis. Demographic, clinical and laboratory data, current clinical manifestations, organs affected by CMV infection, therapeutic management and outcomes were evaluated. The CMV-Ag was considered positive when one cell was detected at least., Results: CMV-Ag was requested in 70 (15.8%) patients with suspicious CMV infection and was positive in 24 (34.3%). The incidence rate of positive CMV-Ag was 4.97% (95% CI 3.1-7.4%). Systemic lupus erythematosus (SLE) (59%), followed by ANCA-related vasculitis (18.2%) and rheumatoid arthritis (9%) were the diseases more associated with positive CMV-Ag. At the time of CMV infection, SLE patients had moderate to severe disease activity, with high frequency of positive anti-dsDNA antibody (69.2%) and complement consumption (61.5%), as well as high doses of corticosteroids and use of immunosuppressants. The main CMV sites involved were lung (45.5%), bone marrow (40.9%) and gut (27.3%). Mortality rate was 45.5%, especially in those with higher doses of daily oral corticosteroids (107 ± 55.4 mg vs. 71.7 ± 46.3 mg; p = 0.07) and lower number of lymphocytes (309 ± 368.2/mm 3 vs. 821 ± 692.9/mm 3 ; p = 0.06)., Conclusions: Our data showed high incidence of CMV-Ag in AIRD patients, particularly those with SLE and greater disease severity. In addition, it was observed high mortality in these patients, highlighting the CMV infection should be included in differential diagnosis.

Systemic lupus erythematosus (SLE), a complex and heterogeneous autoimmune disease, represents a significant challenge for both diagnosis and treatment. Patients with SLE in Latin America face special problems that should be considered when therapeutic guidelines are developed. The objective of the study is to develop clinical practice guidelines for Latin American patients with lupus. Two independent teams (rheumatologists with experience in lupus management and methodologists) had an initial meeting in Panama City, Panama, in April 2016. They selected a list of questions for the clinical problems most commonly seen in Latin American patients with SLE. These were addressed with the best available evidence and summarised in a standardised format following the Grading of Recommendations Assessment, Development and Evaluation approach. All preliminary findings were discussed in a second face-to-face meeting in Washington, DC, in November 2016. As a result, nine organ/system sections are presented with the main findings; an 'overarching' treatment approach was added. Special emphasis was made on regional implementation issues. Best pharmacologic options were examined for musculoskeletal, mucocutaneous, kidney, cardiac, pulmonary, neuropsychiatric, haematological manifestations and the antiphospholipid syndrome. The roles of main therapeutic options (ie, glucocorticoids, antimalarials, immunosuppressant agents, therapeutic plasma exchange, belimumab, rituximab, abatacept, low-dose aspirin and anticoagulants) were summarised in each section. In all cases, benefits and harms, certainty of the evidence, values and preferences, feasibility, acceptability and equity issues were considered to produce a recommendation with special focus on ethnic and socioeconomic aspects. Guidelines for Latin American patients with lupus have been developed and could be used in similar settings., Competing Interests: Competing interests: LBF, BAPE and OAM have been speakers for GlaxoSmithKline (GSK). JCTB has received research grants from GSK. RMX, ON and JFM have received support grants for meetings from GSK. JAGP has been a lecturer for Roche. ERS has received research grants and has been a lecturer for Roche. JFM has been a clinical researcher for Anthera. MHC has received research grants from Roche and is an advisor for Eli Lilly., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Acute exercise increases IL-6, IL-10 and TNF-α levels in healthy subjects. There is no study evaluating the effect of exercise on cytokines level in systemic lupus erythematosus (SLE) patients., Objective: Our aim was to assess IL-10, IL-6 and TNF-α levels at baseline and after acute physical exercise in patients with SLE., Methods: In total, 27 female SLE patients and 30 healthy controls were evaluated. Serum levels of IL-10, IL-6 and TNF-α at baseline and soon after the ergospirometric test were measured by ELISA test. Student's t-tests and Mann-Whitney test were used for intra- and inter-group comparisons; p values <0.05 were considered significant., Results: Patients with SLE presented worse ergospirometric parameters compared with controls: VO2max (25.78 ± 5.51 vs. 32.74 ± 5.85 ml/kg/min, p < 0.001); maximum heart rate (174.18 ± 12.36 vs. 185.15 ± 2.07 bpm, p = 0.001); maximum ventilation (65.51 ± 15.68 vs. 80.48 ± 18.98 l/min, p = 0.001) and maximum speed (7.70 ± 1.24 vs. 9.40 ± 1.22 km/h, p < 0.001). At baseline, SLE patients presented higher levels of IL-6 (2.38 ± 1.70 vs. 1.71 ± 0.29 pg/ml, p = 0.035) and IL-10 (1.09 ± 1.55 vs. 0.30 ± 0.11 pg/ml, p = 0.037) than controls. Acute exercise in controls increased IL-6 level (1.71 ± 0.29 vs. 2.01 ± 0.27 pg/ml, p = 0.003) without change in IL-10 and TNF-α levels. However, no significant change in cytokine levels was observed in SLE patients after acute exercise., Conclusion: This is the first study evaluating the effect of acute exercise on cytokine levels in patients with SLE. In contrast to healthy controls, acute physical exercise did not increase the levels of IL-6 in patients with SLE, and seems to be safe in those patients with inactive or mild active disease.

Objective: The objective of this study was to evaluate the effect of supervised physical exercise on endothelial function, ergospirometric test variables and disease activity in SLE patients., Methods: We conducted a prospective study in which women with SLE who were available to perform physical exercise were allocated to the exercise group (EG) to practise supervised physical exercise for 1 h three times per week for 16 weeks. Those who were not available for this activity were allocated to the control group (CG). Intervention consisted of walking at a heart rate corresponding to the ventilatory 1 threshold obtained from ergospirometry and monitored by a frequency meter. At baseline (T0) and after 16 weeks (T16), patients were assessed for endothelial function by brachial artery (flow-mediated dilation), ergospirometry and disease activity (SLEDAI). Statistical analysis was performed through normality tests, Student's t-test and non-parametric tests for data with non-normal distribution. P < 0.05 was considered significant., Results: Eighteen patients were allocated in the EG and 20 in the CG. After 16 weeks there was an increase in FMD in the EG [6.3 (6.7)% vs 14.1 (9.1)%, P = 0.006] without a change in the CG [8.4 (8.2)% vs 9.4 (5.7)%, P = 0.598]. Regarding the ergospirometric test, we found improvement in exercise tolerance [12.3 (2.4) vs 13.4 (2.6) min, P = 0.027], maximum speed [7.7 (1.0) vs 8.3 (1.2) km/h, P = 0.027] and threshold speed [5.6 (0.7) vs 6.1 (0.9) km/h, P = 0.005] in the EG without a difference in the CG. There was no difference in the SLEDAI score in both groups., Conclusion: Physical exercise is a useful strategy to improve endothelial function and aerobic capacity without worsening disease activity in SLE patients. TRIAL REGISTRATION; ClinicalTrials.gov (http://www.clinicaltrials.gov), NCT01712529.