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1.
Cochrane Database Syst Rev ; 3: CD007478, 2021 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-33687069

RESUMO

BACKGROUND: Lupus erythematosus is an autoimmune disease with significant morbidity and mortality. Cutaneous disease in systemic lupus erythematosus (SLE) is common. Many interventions are used to treat SLE with varying efficacy, risks, and benefits. OBJECTIVES: To assess the effects of interventions for cutaneous disease in SLE. SEARCH METHODS: We searched the following databases up to June 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, Wiley Interscience Online Library, and Biblioteca Virtual em Saude (Virtual Health Library). We updated our search in September 2020, but these results have not yet been fully incorporated. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of interventions for cutaneous disease in SLE compared with placebo, another intervention, no treatment, or different doses of the same intervention. We did not evaluate trials of cutaneous lupus in people without a diagnosis of SLE. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Primary outcomes were complete and partial clinical response. Secondary outcomes included reduction (or change) in number of clinical flares; and severe and minor adverse events. We used GRADE to assess the quality of evidence. MAIN RESULTS: Sixty-one RCTs, involving 11,232 participants, reported 43 different interventions. Trials predominantly included women from outpatient clinics; the mean age range of participants was 20 to 40 years. Twenty-five studies reported baseline severity, and 22 studies included participants with moderate to severe cutaneous lupus erythematosus (CLE); duration of CLE was not well reported. Studies were conducted mainly in multi-centre settings. Most often treatment duration was 12 months. Risk of bias was highest for the domain of reporting bias, followed by performance/detection bias. We identified too few studies for meta-analysis for most comparisons. We limited this abstract to main comparisons (all administered orally) and outcomes. We did not identify clinical trials of other commonly used treatments, such as topical corticosteroids, that reported complete or partial clinical response or numbers of clinical flares. Complete clinical response Studies comparing oral hydroxychloroquine against placebo did not report complete clinical response. Chloroquine may increase complete clinical response at 12 months' follow-up compared with placebo (absence of skin lesions) (risk ratio (RR) 1.57, 95% confidence interval (CI) 0.95 to 2.61; 1 study, 24 participants; low-quality evidence). There may be little to no difference between methotrexate and chloroquine in complete clinical response (skin rash resolution) at 6 months' follow-up (RR 1.13, 95% CI 0.84 to 1.50; 1 study, 25 participants; low-quality evidence). Methotrexate may be superior to placebo with regard to complete clinical response (absence of malar/discoid rash) at 6 months' follow-up (RR 3.57, 95% CI 1.63 to 7.84; 1 study, 41 participants; low-quality evidence). At 12 months' follow-up, there may be little to no difference between azathioprine and ciclosporin in complete clinical response (malar rash resolution) (RR 0.83, 95% CI 0.46 to 1.52; 1 study, 89 participants; low-quality evidence). Partial clinical response Partial clinical response was reported for only one key comparison: hydroxychloroquine may increase partial clinical response at 12 months compared to placebo, but the 95% CI indicates that hydroxychloroquine may make no difference or may decrease response (RR 7.00, 95% CI 0.41 to 120.16; 20 pregnant participants, 1 trial; low-quality evidence). Clinical flares Clinical flares were reported for only two key comparisons: hydroxychloroquine is probably superior to placebo at 6 months' follow-up for reducing clinical flares (RR 0.49, 95% CI 0.28 to 0.89; 1 study, 47 participants; moderate-quality evidence). At 12 months' follow-up, there may be no difference between methotrexate and placebo, but the 95% CI indicates there may be more or fewer flares with methotrexate (RR 0.77, 95% CI 0.32 to 1.83; 1 study, 86 participants; moderate-quality evidence). Adverse events Data for adverse events were limited and were inconsistently reported, but hydroxychloroquine, chloroquine, and methotrexate have well-documented adverse effects including gastrointestinal symptoms, liver problems, and retinopathy for hydroxychloroquine and chloroquine and teratogenicity during pregnancy for methotrexate. AUTHORS' CONCLUSIONS: Evidence supports the commonly-used treatment hydroxychloroquine, and there is also evidence supporting chloroquine and methotrexate for treating cutaneous disease in SLE. Evidence is limited due to the small number of studies reporting key outcomes. Evidence for most key outcomes was low or moderate quality, meaning findings should be interpreted with caution. Head-to-head intervention trials designed to detect differences in efficacy between treatments for specific CLE subtypes are needed. Thirteen further trials are awaiting classification and have not yet been incorporated in this review; they may alter the review conclusions.


Assuntos
Fármacos Dermatológicos/uso terapêutico , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/terapia , Dermatopatias/terapia , Idade de Início , Azatioprina/uso terapêutico , Viés , Fatores Biológicos/uso terapêutico , Cloroquina/efeitos adversos , Cloroquina/uso terapêutico , Técnicas Cosméticas , Ciclosporina/uso terapêutico , Fármacos Dermatológicos/efeitos adversos , Exantema , Feminino , Humanos , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/uso terapêutico , Lúpus Eritematoso Cutâneo/classificação , Lúpus Eritematoso Cutâneo/diagnóstico , Lúpus Eritematoso Cutâneo/terapia , Lúpus Eritematoso Sistêmico/classificação , Lúpus Eritematoso Sistêmico/complicações , Masculino , Medicina Tradicional Chinesa , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Placebos/uso terapêutico , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Dermatopatias/etiologia , Exacerbação dos Sintomas
2.
Ann Rheum Dis ; 79(10): 1333-1339, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32816709

RESUMO

OBJECTIVES: The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 Classification Criteria for systemic lupus erythematosus (SLE) have been validated with high sensitivity and specificity. We evaluated the performance of the new criteria with regard to disease duration, sex and race/ethnicity, and compared its performance against the Systemic Lupus International Collaborating Clinics (SLICC) 2012 and ACR 1982/1997 criteria. METHODS: Twenty-one SLE centres from 16 countries submitted SLE cases and mimicking controls to form the validation cohort. The sensitivity and specificity of the EULAR/ACR 2019, SLICC 2012 and ACR 1982/1997 criteria were evaluated. RESULTS: The cohort consisted of female (n=1098), male (n=172), Asian (n=118), black (n=68), Hispanic (n=124) and white (n=941) patients; with an SLE duration of 1 to <3 years (n=196) and ≥5 years (n=879). Among patients with 1 to <3 years disease duration, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% vs 81%). The EULAR/ACR criteria performed well in men (sensitivity 93%, specificity 96%) and women (sensitivity 97%, specificity 94%). Among women, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% vs 83%) and better specificity than the SLICC criteria (94% vs 82%). Among white patients, the EULAR/ACR criteria had better sensitivity than the ACR criteria (95% vs 83%) and better specificity than the SLICC criteria (94% vs 83%). The EULAR/ACR criteria performed well among black patients (sensitivity of 98%, specificity 100%), and had better sensitivity than the ACR criteria among Hispanic patients (100% vs 86%) and Asian patients (97% vs 77%). CONCLUSIONS: The EULAR/ACR 2019 criteria perform well among patients with early disease, men, women, white, black, Hispanic and Asian patients. These criteria have superior sensitivity than the ACR criteria and/or superior specificity than the SLICC criteria across many subgroups.


Assuntos
Lúpus Eritematoso Sistêmico/classificação , Índice de Gravidade de Doença , Feminino , Humanos , Masculino , Seleção de Pacientes , Sensibilidade e Especificidade
3.
Ann Rheum Dis ; 79(7): 943-950, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32321721

RESUMO

OBJECTIVES: Remission in systemic lupus erythematosus (SLE) is defined through a combination of 'clinical SLE Disease Activity Index (cSLEDAI)=0', 'physician's global assessment (PGA) <0.5' and 'prednisone (PDN) ≤5 mg/day'. We investigated the performance of these items, alone or in combination, in defining remission and in predicting SLICC/ACR Damage Index. METHODS: We tested seven potential definitions of remission in SLE patients followed-up for ≥5 years: PDN ≤5 mg/day; PGA <0.5; cSLEDAI=0; PGA <0.5 plus PDN ≤5 mg/day; cSLEDAI=0 plus PGA <0.5; cSLEDAI=0 plus PDN ≤5 mg/day; cSLEDAI=0 plus PDN ≤5 mg/day plus PGA <0.5. The effect of these definitions on damage was evaluated by Poisson regression analysis; the best performance was identified as the lowest Akaike and Bayesian information criterion (AIC and BIC). Positive and negative predictive values in identifying no damage increase were calculated. RESULTS: We included 646 patients (mean±SD disease duration 9.2±6.9 years). At multivariate analysis, ≥2 consecutive year remission according to all definitions protected against damage (OR, 95% CI: PGA <0.5 0.631, 0.444 to 0.896; cSLEDAI=0 0.531, 0.371 to 0.759; PGA <0.5 plus PDN ≤5 mg/day 0.554, 0.381 to 0.805; cSLEDAI=0 plus PGA <0.5 0.574, 0.400 to 0.826; cSLEDAI=0 plus PDN ≤5 mg/day 0.543, 0.376 to 0.785; cSLEDAI=0 plus PDN ≤5 mg/day plus PGA <0.5 0.532, 0.363 to 0.781, p<0.01 for all), except PDN ≤5 mg/day, which required four consecutive years (OR 0.534, 95% CI 0.325 to 0.877, p=0.013). Positive and negative predictive values were similar; however, cSLEDAI=0 showed the best performance (AIC 1082.90, BIC 1109.72, p<0.0001). Adding PGA <0.5 and/or PDN ≤5 mg/day to cSLEDAI=0 decreased remission duration (-1.8 and -1.5 year/patient, respectively) without increasing cSLEDAI=0 performance in predicting damage accrual. CONCLUSIONS: cSLEDAI=0 is the most attainable definition of remission, while displaying the best performance in predicting damage progression in the short-to-mid-term follow-up.


Assuntos
Lúpus Eritematoso Sistêmico/classificação , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Avaliação de Resultados em Cuidados de Saúde/métodos , Índice de Gravidade de Doença , Adulto , Anti-Inflamatórios/administração & dosagem , Teorema de Bayes , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prednisona/administração & dosagem , Análise de Regressão , Indução de Remissão
5.
Lupus ; 29(3): 344-350, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32046576

RESUMO

OBJECTIVE: Systemic lupus erythematosus (SLE) is a complex multi-systemic autoimmune disease with variable levels of activity that may wax and wane within the same patient over the years. In view of the scarcity of data about lupus in the East Malaysian population, we aimed to study the disease activity and damage index in patients with SLE hospitalized in a tertiary center in Sabah, East Malaysia. METHODS: We retrospectively studied all patients with SLE admitted from 1 January 2013 to 31 December 2015. Demographic data, clinical features, treatment received, SLEDAI and SLICC/ACR (Systemic Lupus International Collaborating Clinics/American College of Rheumatology) criteria and outcomes were collected. RESULTS: There were 108 patients studied whereby 88.9% were females. They had a mean age of 31.4 ± 11.02 years at admission and were multiethnic in origin. The mean number of ACR criteria for SLE was 5.03 ± 1.5 at the time of diagnosis. There were 158 hospitalizations during the 3 years. The main causes of hospitalization were flare of SLE (66.5%), infection (57.6%), renal biopsy (15.5%) and others (11.4%). Active nephritis (65%), cutaneous (44.4%) and hematological involvement (40.2%) were the three commonest manifestations. There was concurrent flare of SLE and infection in 41.1% of the admissions. The mean SLEDAI score at admission was 10.8 ± 7.20, with a mean SLEDAI of 9.3 ± 6.9 in those without damage and 11.9 ± 7.21 in those with damage (p-value = 0.026). The median SLICC score was 1 with a mean of 0.93 ± 1.07. There were nine deaths (5.6%) during the study period and all patients were females. Compared with those who survived, they had a significantly higher SLEDAI score of 15.80 ± 8.2 (p-value = 0.0207) and a SLICC score of 2.70 ± 1.6 (p-value <0.001). CONCLUSION: SLE is more common among the indigenous population of Sabah, the Kadazan-Dusun, which has not been shown before this study. Disease characteristics were, however, similar to reports from the Asia-Pacific region. Acute flare of SLE and infection remained the main causes of admission and readmissions and was present in 44.4% of the mortalities in our cohort.


Assuntos
Hospitalização/estatística & dados numéricos , Lúpus Eritematoso Sistêmico/classificação , Lúpus Eritematoso Sistêmico/diagnóstico , Adolescente , Adulto , Grupo com Ancestrais do Continente Asiático , Feminino , Humanos , Malásia , Masculino , Estudos Retrospectivos , Reumatologia/normas , Índice de Gravidade de Doença , Sociedades Médicas/normas , Adulto Jovem
6.
Ann Rheum Dis ; 79(2): 232-241, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31704720

RESUMO

OBJECTIVES: Classification criteria are biased towards classifying long-standing disease. We compared the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR)-2019, Systemic Lupus International Collaborating Clinics (SLICC)-2012 and ACR-1997 criteria in an early (median 48 months) systemic lupus erythematosus (SLE) cohort. METHODS: Patients diagnosed with SLE (n=690) or control diseases (n=401). Sensitivity, specificity of the criteria and time-to-classification were calculated. Modified classification algorithms were derived from a random 80% and validated in the remaining 20% of the dataset running multiple iterations. RESULTS: At last assessment, sensitivities of ACR-1997, SLICC-2012 and EULAR/ACR-2019 criteria were 85.7%, 91.3% and 88.6%, with specificities 93.0%, 93.8% and 97.3%, respectively. Both SLICC and EULAR/ACR enabled earlier classification. Only 76.7% of patients with SLE met all three criteria suggesting non-overlapping groups. Notably, unclassified patients had high prevalence of British Isles Lupus Assessment Group moderate/severe manifestations (43.3%-60%) and SLICC/ACR organ damage (30%-50%). At diagnosis, criteria missed 25.6%-30.5% of patients. Modification of EULAR/ACR and SLICC algorithms to include hypocomplementaemia and/or positive anti-phospholipid antibodies as alternative entry criterion, and/or allow classification with fewer clinical criteria from multiple organs, increased their sensitivity at diagnosis (median 82.0% and 86.2%) and overall (93.7% and 97.1%) with modest decreases in specificity. Importantly, patients who were still missed by the modified criteria had lower incidence of major organ involvement, use of immunosuppressive/biological therapies and organ damage. CONCLUSIONS: The SLICC and EULAR/ACR are more sensitive than the ACR and the EULAR/ACR criteria have superior specificity in early SLE, although patients with significant disease can be missed. Combination and/or modification of the classification algorithms may enhance their sensitivity, allowing earlier classification and treatment of more patients with high disease burden.


Assuntos
Lúpus Eritematoso Sistêmico/classificação , Lúpus Eritematoso Sistêmico/diagnóstico , Reumatologia/métodos , Índice de Gravidade de Doença , Avaliação de Sintomas/métodos , Adulto , Algoritmos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Reumatologia/normas , Sensibilidade e Especificidade , Avaliação de Sintomas/normas
7.
Arthritis Care Res (Hoboken) ; 72(5): 607-614, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-30932354

RESUMO

Incomplete systemic lupus (iSLE) is an acknowledged condition of patients with clinical signs of lupus who do not fulfill classification criteria for SLE. Some patients with iSLE have persistent mild disease, but others have serious organ involvement, and up to 55% progress to established SLE. Research on this subject could reveal predictive or diagnostic biomarkers for SLE. Ideally, it would become possible to discern those patients with critical organ involvement or a high risk for progression to SLE. This high-risk group might benefit from early treatment, which would preferably be confirmed in randomized controlled trials. This process would, however, require agreement on a definition of iSLE. The Systemic Lupus International Collaborating Clinics (SLICC) classification criteria was composed in order to diagnose SLE earlier. The present review outlines the clinical characteristics of iSLE after introduction of SLICC criteria and furthermore proposes a definition of iSLE with the aim of discriminating the high-risk group from those with a lower risk.


Assuntos
Técnicas de Apoio para a Decisão , Lúpus Eritematoso Sistêmico/diagnóstico , Terminologia como Assunto , Adulto , Progressão da Doença , Feminino , Humanos , Lúpus Eritematoso Sistêmico/classificação , Lúpus Eritematoso Sistêmico/terapia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco , Índice de Gravidade de Doença
8.
Semin Arthritis Rheum ; 49(3S): S14-S17, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31779843

RESUMO

Supported by both the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) from the beginning, a large transatlantic, and in many phases worldwide, project has led to new classification criteria for systemic lupus erythematosus (SLE). The project had ambitious goals, particularly maintaining the high specificity of the ACR criteria, while reaching a sensitivity close to the Systemic Lupus International Collaborating Clinics (SLICC) 2012 criteria. The validation data suggest that the new criteria reached this goal, with a specificity of 93% (as for the ACR criteria) and a sensitivity of 96% (vs 97% for the SLICC criteria). The new EULAR/ACR classification criteria use positive antinuclear antibodies (ANA) as an entry criterion and have weighted items, ranging from 2 (for delirium, non-infectious fever and anti-phospholipid antibodies) to 10 (for class III or IV lupus nephritis). The cut-off for classification is 10, reached by class III/IV nephritis alone. Items are organized in domains, within which only the highest item is to be counted. Instead of many defined exclusions, one rule is used for all, namely that items are to be attributed to SLE and counted only if there is no more likely alternative diagnosis. These criteria are now expected to be externally validated in various other cohorts. The team spirit and collegiality characteristic for this EULAR/ACR criteria effort will hopefully facilitate future international projects on SLE.


Assuntos
Autoimunidade , Lúpus Eritematoso Sistêmico/classificação , Reumatologia , Sociedades Médicas , Europa (Continente) , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Estados Unidos
9.
Autoimmun Rev ; 18(12): 102400, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31639513

RESUMO

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with highly variable clinical and immunological manifestations. In the classification of patients with this condition, the presence of an antinuclear antibody (ANA) is an important element, with new criteria from the American College of Rheumatology and European League against Rheumatism positioning ANA positivity by an immunofluorescence assay on HEp2-cells (HEp2-IFA) or by an equivalent solid phase assay as the entry criterion. This positioning is based on assumptions about the frequency of ANA positivity in SLE as well as the reliability of the assays. Studies indicate that these assumptions are still a matter of uncertainty since both types of assay show considerable variability and patients with SLE may display negative results in ANA testing. These findings suggest caution in positioning ANA positivity as an entry criterion for classification and point to the value of alternative serological approaches for ANA determinations.


Assuntos
Anticorpos Antinucleares/imunologia , Lúpus Eritematoso Sistêmico/classificação , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Anticorpos Antinucleares/análise , Feminino , Imunofluorescência , Humanos , Imunoensaio/métodos , Imunoensaio/normas , Reprodutibilidade dos Testes
10.
Sci Rep ; 9(1): 15502, 2019 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-31664045

RESUMO

Systemic lupus erythematosus (SLE) is a heterogeneous disease with unpredictable patterns of activity. Patients with similar activity levels may have different prognosis and molecular abnormalities. In this study, we aimed to measure the main differences in drug-induced gene expression signatures across SLE patients and to evaluate the potential for clinical data to build a machine learning classifier able to predict the SLE subset for individual patients. SLE transcriptomic data from two cohorts were compared with drug-induced gene signatures from the CLUE database to compute a connectivity score that reflects the capability of a drug to revert the patient signatures. Patient stratification based on drug connectivity scores revealed robust clusters of SLE patients identical to the clusters previously obtained through longitudinal gene expression data, implying that differential treatment depends on the cluster to which patients belongs. The best drug candidates found, mTOR inhibitors or those reducing oxidative stress, showed stronger cluster specificity. We report that drug patterns for reverting disease gene expression follow the cell-specificity of the disease clusters. We used 2 cohorts to train and test a logistic regression model that we employed to classify patients from 3 independent cohorts into the SLE subsets and provide a clinically useful model to predict subset assignment and drug efficacy.


Assuntos
Lúpus Eritematoso Sistêmico/genética , Transcriptoma/efeitos dos fármacos , Estudos de Casos e Controles , Análise por Conglomerados , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/classificação , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Masculino , Índice de Gravidade de Doença
11.
Croat Med J ; 60(4): 333-344, 2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31483119

RESUMO

AIM: To validate Systemic Lupus International Collaborating Clinics (SLICC)-12 and American College of Rheumatology (ACR)-97 classification criteria on a patient cohort from the University Hospital Center Zagreb. METHODS: This retrospective study, conducted from 2014 to 2016, involved 308 patients with systemic lupus erythematosus (SLE) (n=146) and SLE-allied conditions (n=162). Patients' medical charts were evaluated by an expert rheumatologist to confirm the clinical diagnosis, regardless of the number of the ACR-97 criteria met. Overall sensitivity and specificity, as well as the sensitivity and specificity according to disease duration, were compared between ACR-97 and SLICC-12 classifications. Predictive value for SLE for both classifications was assessed using logistic regression and receiver operating characteristic (ROC) curves. RESULTS: The SLICC-12 criteria had significantly higher sensitivity in early disase, which increased with disease duration. The ACR-97 criteria had higher specificity. The specificity of the SLICC-12 criteria was low and decreased with disease duration. Regression analysis demonstrated the superiority of the SLICC-12 classification criteria over the ACR-97 criteria, with areas under the ROC curve of 0.801 and 0.780, respectively. CONCLUSION: Although the SLICC-12 criteria were superior to the ACR-97 and were more sensitive for diagnosing early SLE, their specificity in our population was too low. The sensitivity of the SLICC-12 classification is increased by better defined clinical features within each criterion. Our results contribute to the current initiative for developing new criteria for SLE.


Assuntos
Lúpus Eritematoso Sistêmico/classificação , Lúpus Eritematoso Sistêmico/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Hospitais Universitários , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Curva ROC , Encaminhamento e Consulta , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Adulto Jovem
12.
Ann Rheum Dis ; 78(9): 1151-1159, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31383717

RESUMO

OBJECTIVE: To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: This international initiative had four phases. (1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort and a patient survey. (2) Criteria reduction by Delphi and nominal group technique exercises. (3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. (4) Refinement of weights and threshold scores in a new derivation cohort of 1001 subjects and validation compared with previous criteria in a new validation cohort of 1270 subjects. RESULTS: The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in seven clinical (constitutional, haematological, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and three immunological (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria. CONCLUSION: These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered and weighted criteria reflect current thinking about SLE and provide an improved foundation for SLE research.


Assuntos
Lúpus Eritematoso Sistêmico/classificação , Doenças Reumáticas , Reumatologia , Sociedades Médicas , Humanos
13.
Arthritis Rheumatol ; 71(9): 1400-1412, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31385462

RESUMO

OBJECTIVE: To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: This international initiative had four phases. 1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort, and a patient survey. 2) Criteria reduction by Delphi and nominal group technique exercises. 3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. 4) Refinement of weights and threshold scores in a new derivation cohort of 1,001 subjects and validation compared with previous criteria in a new validation cohort of 1,270 subjects. RESULTS: The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in 7 clinical (constitutional, hematologic, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and 3 immunologic (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria. CONCLUSION: These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered, and weighted criteria reflects current thinking about SLE and provides an improved foundation for SLE research.


Assuntos
Lúpus Eritematoso Sistêmico/classificação , Reumatologia/normas , Adulto , Anticorpos Antinucleares/sangue , Anticorpos Antinucleares/imunologia , Anticorpos Antifosfolipídeos/sangue , Anticorpos Antifosfolipídeos/imunologia , Autoanticorpos/sangue , Autoanticorpos/imunologia , Estudos de Coortes , Proteínas do Sistema Complemento/análise , Técnicas de Apoio para a Decisão , Técnica Delfos , Europa (Continente) , Feminino , Humanos , Cooperação Internacional , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Sociedades Médicas , Estados Unidos
14.
Autoimmun Rev ; 18(10): 102361, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31401343

RESUMO

Systemic lupus erythematosus (SLE) is a severe lifelong multisystem autoimmune disease characterized by the presence of autoantibodies targeting nuclear autoantigens, increased production of type I interferon and B cell abnormalities. Clinical presentation of SLE is extremely heterogeneous and different groups of disease are likely to exist. Recently, childhood-onset SLE (cSLE) cases have been linked to single gene mutations, defining the concept of monogenic or Mendelian lupus. Genes associated with Mendelian lupus can be grouped in at least three functional categories. First, complement deficiencies represent the main cause of monogenic lupus and its components are involved in the clearance of dying cells, a mechanism also called efferocytosis. Mutations in extracellular DNASE have been also identified in cSLE patients and represent additional causes leading to defective clearance of nucleic acids and apoptotic bodies. Second, the study of Aicardi-Goutières syndromes has introduced the concept of type-I interferonopathies. Bona fide lupus syndromes have been associated to this genetic condition, driven by defective nucleic acids metabolism or innate sensors overactivity. Interferon signalling anomalies can be detected and monitored during therapies, such as Janus-kinase (JAK) inhibitors. Third, tolerance breakdown can occur following genetic mutations in B and/or T cell expressing key immunoregulatory molecules. Biallelic mutations in PRKCD are associated to lupus and lymphoproliferative diseases as PKC-δ displays proapoptotic activity and is crucial to eliminate self-reactive transitional B cells. Here we review the literature of the emerging field of Mendelian lupus and discuss the physiopathological learning from these inborn errors of immunity. In addition, clinical and biological features are highlighted as well as specific therapies that have been tested in these genetic contexts.


Assuntos
Predisposição Genética para Doença , Lúpus Eritematoso Sistêmico/classificação , Lúpus Eritematoso Sistêmico/genética , Polimorfismo Genético , Humanos , Lúpus Eritematoso Sistêmico/imunologia
15.
Lancet ; 393(10188): 2332-2343, 2019 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-31180030

RESUMO

Systemic lupus erythematosus (SLE) is an autoimmune disease characterised by the loss of self-tolerance and formation of nuclear autoantigens and immune complexes resulting in inflammation of multiple organs. The clinical presentation of SLE is heterogeneous, can involve one or more organs, including the skin, kidneys, joints, and nervous system, and take a chronic or relapsing and remitting disease course. SLE is most common in women and in those of non-white ethnicity. Because of the multitude of presentations, manifestations, and serological abnormalities in patients with SLE, diagnosis can be challenging. Therapeutic approaches predominantly involve immunomodulation and immunosuppression and are targeted to the specific organ manifestation, with the aim of achieving low disease activity. Despite many treatment advances and improved diagnostics, SLE continues to cause substantial morbidity and premature mortality. Current management strategies, although helpful, are limited by high failure rates and toxicity. An overreliance on corticosteroid therapy contributes to much of the long-term organ damage. In this Seminar, we outline the classification criteria for SLE, current treatment strategies and medications, the evidence supporting their use, and explore potential future therapies.


Assuntos
Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico , Adulto , Feminino , Humanos , Lúpus Eritematoso Sistêmico/classificação , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/mortalidade , Lúpus Eritematoso Sistêmico/fisiopatologia , Resultado do Tratamento
16.
Lancet ; 393(10188): 2344-2358, 2019 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-31180031

RESUMO

The heterogeneity of systemic lupus erythematosus (SLE), long recognised by clinicians, is now challenging the entire lupus community, from geneticists to clinical investigators. Although the outlook for patients with SLE has greatly improved, many unmet needs remain, chief of which is the development of safer and more efficacious therapies. To develop innovative therapies, a far better understanding of SLE pathogenesis as it relates to the array of clinical phenotypes is needed. Additionally, to efficiently achieve these goals, the lupus community needs to refine existing clinical research tools and better adapt them to overcome the obstacles created by the heterogeneity of manifestations. Here, we review progress towards the ultimate goal of safely reducing disease activity and preventing damage accrual and death. We discuss the new classification criteria from the European League Against Rheumatism and American College of Rheumatology, novel definitions of remission and low lupus disease activity, and new proposals for the histological classification of lupus nephritis. Recommendations for the treatment of SLE and novel approaches to drug development hold much promise to further enhance SLE outcomes.


Assuntos
Lúpus Eritematoso Sistêmico/tratamento farmacológico , Feminino , Humanos , Lúpus Eritematoso Sistêmico/classificação , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Indução de Remissão , Reumatologia/métodos , Reumatologia/tendências , Índice de Gravidade de Doença
18.
Lupus ; 28(6): 778-782, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31046572

RESUMO

In a joint effort, the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) recently proposed new criteria for the classification of systemic lupus erythematosus (SLE) with the overarching goal to identify potential participants for clinical studies. Herein, we present the first independent evaluation of these criteria in comparison with older classification grounds using an adult Scandinavian study population of confirmed SLE cases and individuals with SLE-mimicking conditions. We included 56 confirmed SLE cases meeting the 1982 ACR criteria (ACR-82) and/or the Fries "diagnostic principle" (antinuclear antibodies on at least one occasion plus involvement of at least two defined organ systems) and 55 controls with possible systemic autoimmune disease, including the presence of any SLE-related autoantibody. The proposed EULAR/ACR criteria showed a diagnostic sensitivity of 93% (95% confidence interval (CI), 0.83-0.98) compared with 83% (95% CI, 0.72-0.91) for the updated ACR criteria from 1997. The diagnostic accuracy of all tested classification grounds was fairly similar, achieving approximately 85%. However, the disease specificity of the EULAR/ACR criteria reached only 73% (95% CI, 0.59-0.83), which was comparable with the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria, 75% (95% CI, 0.61-0.85), but clearly lower than for ACR-82, 94% (95% CI, 0.83-0.99). In this first independent evaluation of a limited number of cases, we found comparable results with respect to diagnostic sensitivity, specificity and accuracy regarding the SLICC-12 and the proposed EULAR/ACR classification criteria. However, their specificity for SLE appeared to be lower compared with ACR-82.


Assuntos
Lúpus Eritematoso Sistêmico/classificação , Lúpus Eritematoso Sistêmico/diagnóstico , Reumatologia/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Suécia , Adulto Jovem
19.
Adv Rheumatol ; 59(1): 20, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-31092290

RESUMO

BACKGROUND: To date there are no specific classification criteria for childhood-onset systemic lupus erythematosus (cSLE). This study aims to compare the performance among the American College of Rheumatology (ACR) 1997, the Systemic Lupus International Collaborating Clinics criteria (SLICC) and the new European League Against Rheumatism (EULAR)/ACR criteria, in a cSLE cohort. METHODS: We conducted a medical chart review study of cSLE cases and controls with defined rheumatic diseases, both ANA positive, to establish each ACR1997, SLICC and EULAR/ACR criterion fulfilled, at first visit and 1-year-follow-up. RESULTS: Study population included 122 cSLE cases and 89 controls. At first visit, SLICC criteria had higher sensitivity than ACR 1997 (89.3% versus 70.5%, p <  0.001), but similar specificity (80.9% versus 83.2%, p = 0.791), however performance was not statistically different at 1-year-follow-up. SLICC better scored in specificity compared to EULAR/ACR score ≥ 10 at first visit (80.9% versus 67.4%, p = 0.008) and at 1-year (76.4% versus 58.4%, p = 0.001), although sensitivities were similar. EULAR/ACR criteria score ≥ 10 exhibited higher sensitivity than ACR 1997 (87.7% versus 70.5%, p <  0.001) at first visit, but comparable at 1-year, whereas specificity was lower at first visit (67.4% versus 83.2%, p = 0.004) and 1-year (58.4% versus 76.4%, p = 0.002). A EULAR/ACR score ≥ 13 against a score ≥ 10, resulted in higher specificity, positive predictive value, and cut-off point accuracy. Compared to SLICC, a EULAR/ACR score ≥ 13 resulted in lower sensitivity at first visit (76.2% versus 89.3%, p <  0.001) and 1-year (91% versus 97.5%, p = 0.008), but similar specificities at both assessments. When compared to ACR 1997, a EULAR/ACR total score ≥ 13, resulted in no differences in sensitivity and specificity at both observation periods. CONCLUSIONS: In this cSLE population, SLICC criteria better scored at first visit and 1-year-follow-up. The adoption of a EULAR/ACR total score ≥ 13 in this study, against the initially proposed ≥10 score, was most appropriate to classify cSLE. Further studies are necessary to address if SLICC criteria might allow fulfillment of cSLE classification earlier in disease course and may be more inclusive of cSLE subjects for clinical studies.


Assuntos
Lúpus Eritematoso Sistêmico/classificação , Adolescente , Idade de Início , Anticorpos Antinucleares/análise , Estudos de Casos e Controles , Criança , Pré-Escolar , Europa (Continente) , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Reumatologia , Sensibilidade e Especificidade , Estados Unidos
20.
Lupus ; 28(5): 597-606, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30845880

RESUMO

OBJECTIVE: Further prospective study is needed to elucidate the etiology and natural history of systemic lupus erythematosus development. The clinical complexity of this heterogeneous disease makes study design challenging. Our objective was to ascertain useful screening factors for identifying at-risk individuals for follow-up rheumatologic assessment or inclusion in prospective studies. METHODS: We attempted to re-contact 3823 subjects with a family history of systemic lupus erythematosus, who did not meet American College of Rheumatology systemic lupus erythematosus classification at a baseline study visit; 436 agreed to follow-up participation an average of 6.3 years after baseline. In total, 56 of these individuals had transitioned to classified systemic lupus erythematosus (≥ 4 cumulative American College of Rheumatology criteria, verified by medical record review) by the time of follow up. Generalized estimating equations assessed associations between our dichotomous outcome of transitioning to systemic lupus erythematosus with baseline characteristics, including ANA positivity, Connective Tissue Disease Screening questionnaire systemic lupus erythematosus score, and number of American College of Rheumatology criteria. We analyzed predictive accuracy of characteristics on transitioning. RESULTS: ANA positivity, Connective Tissue Disease Screening questionnaire systemic lupus erythematosus score categorization of possible or probable systemic lupus erythematosus, and greater number of American College of Rheumatology criteria at baseline were each associated with transitioning to systemic lupus erythematosus classification. Being ANA positive and having confirmed immunologic criteria at baseline had the highest positive predictive value and specificity for transitioning to systemic lupus erythematosus. American College of Rheumatology Connective Tissue Disease Screening questionnaire systemic lupus erythematosus score categorization of possible or probable systemic lupus erythematosus had a better positive predictive value, negative predictive value, sensitivity, and specificity than ANA positivity. CONCLUSION: Given limited resources, identifying individuals for follow up based on the systemic lupus erythematosus portion of the Connective Tissue Disease Screening questionnaire could be an efficient way to identify family members at highest risk of disease transition.


Assuntos
Autoanticorpos/sangue , Mediadores da Inflamação/sangue , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/diagnóstico , Adulto , Idoso , Progressão da Doença , Feminino , Seguimentos , Humanos , Lúpus Eritematoso Sistêmico/classificação , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Medição de Risco , Índice de Gravidade de Doença , Estados Unidos
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