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1.
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
2.
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
3.
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
4.
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
5.
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
6.
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
7.
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
8.
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
9.
Ann Rheum Dis ; 78(5): 634-640, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30692164

RESUMO

European League Against Rheumatism and are jointly supporting multiphase development of systemic lupus erythematosus (SLE) classification criteria based on weighted criteria and a continuous probability scale. Prior steps included item generation, item reduction and hierarchical organisation of candidate criteria using an evidence-based approach. Our objectives were to determine relative weights using multicriteria decision analysis (MCDA) and to set a provisional threshold score for SLE classification. An SLE Expert Panel (8 European, 9 North American) submitted 164 real, unique cases with a wide range of SLE probability in a standardised format. Using the candidate criteria, experts scored and rank-ordered 20 representative cases. At an in-person meeting, experts reviewed inter-rater reliability of scoring, further refined criteria definitions and participated in an MCDA exercise. Based on expert consensus decisions on pairwise comparisons of criteria, 1000minds software calculated criteria weights and rank-ordered the remaining 144 cases based on their additive scores. The score of the lowest-ranked case for which complete expert consensus was achieved defined the provisional threshold classification score. Inter-rater reliability of scoring cases with the candidate criteria was good. MCDA involved 74 pairwise decisions and was repeated for the arthritis and mucocutaneous domains when the initial ranking of some cases did not match expert opinion. After criteria weights and additive scores were recalculated once, experts reached consensus for SLE classification for all cases scoring>83. Using an iterative process, the candidate criteria definitions were refined, preliminary weights were calculated and a provisional threshold score for SLE classification was determined.


Assuntos
Técnicas de Apoio para a Decisão , Lúpus Eritematoso Sistêmico/classificação , Reumatologia/normas , Consenso , Humanos , Reprodutibilidade dos Testes , Reumatologia/métodos
10.
Arthritis Rheumatol ; 71(1): 91-98, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30035365

RESUMO

OBJECTIVE: Systemic lupus erythematosus (SLE) presents with nonspecific signs and symptoms that are also found in other conditions. This study aimed to evaluate manifestations at disease onset and to compare early SLE manifestations to those of diseases mimicking SLE. METHODS: Academic lupus centers in Asia, Europe, North America, and South America collected baseline data on patients who were referred to them during the previous 3 years for possible SLE and who had a symptom duration of <1 year. Clinical and serologic manifestations were compared between patients diagnosed as having SLE and those diagnosed as having SLE-mimicking conditions. Diagnostic performance of the 1997 American College of Rheumatology (ACR) SLE classification criteria and the 2012 Systemic Lupus International Collaborating Clinics (SLICC) SLE classification criteria was tested. RESULTS: Data were collected on 389 patients with early SLE and 227 patients with SLE-mimicking conditions. Unexplained fever was more common in early SLE than in SLE-mimicking conditions (34.5% versus 13.7%, respectively; P < 0.001). Features less common in early SLE included Raynaud's phenomenon (22.1% versus 48.5%; P < 0.001), sicca symptoms (4.4% versus 34.4%; P < 0.001), dysphagia (0.3% versus 6.2%; P < 0.001), and fatigue (28.3% versus 37.0%; P = 0.024). Anti-double-stranded DNA, anti-ß2 -glycoprotein I antibodies, positive Coombs' test results, autoimmune hemolytic anemia, hypocomplementemia, and leukopenia were more common in early SLE than in SLE-mimicking conditions. Symptoms detailed in the ACR and SLICC classification criteria were significantly more frequent among those with early SLE. Fewer patients with early SLE were not identified as having early SLE with use of the SLICC criteria compared to the ACR criteria (16.5% versus 33.9%), but the ACR criteria demonstrated higher specificity than the SLICC criteria (91.6% versus 82.4%). CONCLUSION: In this multicenter cohort, clinical manifestations that could help to distinguish early SLE from SLE-mimicking conditions were identified. These findings may aid in earlier SLE diagnosis and provide information for ongoing initiatives to revise SLE classification criteria.


Assuntos
Doenças Autoimunes/diagnóstico , Lúpus Eritematoso Sistêmico/diagnóstico , Síndrome de Sjogren/diagnóstico , Adulto , Anemia Hemolítica Autoimune/etiologia , Anticorpos Antinucleares , Síndrome Antifosfolipídica/diagnóstico , Artrite Reumatoide/diagnóstico , Autoanticorpos/imunologia , Estudos de Coortes , Proteínas do Sistema Complemento/imunologia , Teste de Coombs , DNA/imunologia , Transtornos de Deglutição/etiologia , Diagnóstico Diferencial , Feminino , Febre de Causa Desconhecida/etiologia , Hepatite Autoimune/diagnóstico , Humanos , Leucopenia/etiologia , Doenças Pulmonares Intersticiais/diagnóstico , Lúpus Eritematoso Sistêmico/classificação , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Doença Mista do Tecido Conjuntivo/diagnóstico , Doença de Raynaud/etiologia , Escleroderma Sistêmico/diagnóstico , Síndrome de Sjogren/etiologia , Tireoidite Autoimune/diagnóstico , Doenças do Tecido Conjuntivo Indiferenciado/diagnóstico , Adulto Jovem , beta 2-Glicoproteína I/imunologia
11.
Lupus ; 28(1): 11-18, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30463470

RESUMO

OBJECTIVE: We compared the 1997 update of the 1982 American College of Rheumatology (ACR-97) and the 2012 Systemic Lupus International Collaborating Clinics (SLICC-12) criteria, for earlier classification of systemic lupus erythematosus (SLE) in a multiethnic urban Asian SLE population. METHODS: Patients from a retrospective, nested case-control study of the influence of lupus nephritis on mortality in SLE were studied. For each patient, dates of first manifestations of each criteria (both ACR-97 and SLICC-12) were recorded, and the date of disease classification using ACR-97 or SLICC-12 criteria was compared to determine which criteria resulted in earlier classification. RESULTS: Among 182 SLE patients (74.2% Chinese, 18.1% Malay, 4.4% Indian and 3.3% Other ethnicities), 10 (5.5%) did not fulfill the ACR-97 criteria and 2 (1.1%) did not fulfill the SLICC-12 criteria. Using the SLICC-12 criteria, 18% of subjects showed earlier classification, whereas 7% of subjects showed earlier classification using the ACR-97 criteria. The SLICC hematologic criteria of "Leukopenia or lymphopenia" contributed most significantly to earlier diagnosis by SLICC-12. "Leukopenia or lymphopenia'' was present in 59% (19/32) of patients where SLICC-12 criteria allowed for earlier classification than ACR-97, compared with 15.4% (2/13) of patients where ACR-97 allowed earlier classification than SLICC-12 ( p = 0.02). The immunologic criterion that is considered a strength of the SLICC-12 criteria did not appear to contribute significantly to earlier diagnosis in this study. CONCLUSION: SLICC-12 criteria allow for earlier classification of SLE in a multiethnic cohort of Asian patients, supporting the validity of the SLICC-12 criteria and its use in clinical care and research.


Assuntos
Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Lúpus Eritematoso Sistêmico/classificação , Lúpus Eritematoso Sistêmico/diagnóstico , Reumatologia/normas , Estudos de Casos e Controles , Humanos , Estudos Retrospectivos , Índice de Gravidade de Doença , Singapura , Sociedades Médicas , População Urbana
13.
Z Gastroenterol ; 56(10): 1257-1266, 2018 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-30103221

RESUMO

INTRODUCTION: Systemic lupus erythematodes (SLE) represents an autoimmune disease with a highly variable clinical course affecting numerous organs. Hepatic manifestation seems to be rare. It is not clear whether hepatic disease in SLE is of any prognostic importance or whether it correlates with disease activity. METHODS: Our patient cohort included 172 patients with proven SLE, all treated at Bogenhausen Hospital between 01.2009 and 12.2015. Retrospectively, all admissions as inpatients and outpatients were analyzed (n = 671; mean 3.9 per patient). Liver damage was diagnosed by evaluation of laboratory parameters on the basis of pathological liver enzymes and by imaging methods. Disease activity of SLE was calculated by using European Consensus Lupus Activity Measurement-(ECLAM-)Score. Additionally, parameters of SLE including disease duration, organ damage and immune suppressive medication and their possible association with hepatopathy were analyzed. RESULTS: Elevated liver parameters (ASAT, ALAT, GGT, AP) indicating liver damage were detectable in 109 patients (63.4 % of total population) demonstrating significant association with disease activity (on the basis of ECLAM-score, p < 0.001), duration of treatment, frequency of admissions (p < 0.01, respectively), number of used immunosuppressive agents (p < 0.018), increased blood sedimentation rate (p < 0.001) and reduction of serum complement (p < 0.03). Abnormal ultrasound findings of the liver (e. g., non-alcoholic fatty liver disease) were diagnosed in 19.8 %. DISCUSSION: Elevated liver parameters occur frequently in patients with SLE, especially in context with increased disease activity (on the basis of ECLAM-Score or intensified immunosuppressive therapy) and prolonged course of the disease. Liver enzymes should be obtained regularly in patients with SLE and, if necessary, further diagnostic steps should be initiated. Further prospective studies might clarify whether abnormal liver parameters must be included in activity indices to judge disease activity in SLE.


Assuntos
Hepatopatias , Lúpus Eritematoso Sistêmico , Índice de Gravidade de Doença , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hepatopatias/complicações , Hepatopatias/epidemiologia , Lúpus Eritematoso Sistêmico/classificação , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
14.
Arthritis Rheumatol ; 70(12): 2025-2035, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29938934

RESUMO

OBJECTIVE: The highly heterogeneous clinical presentation of systemic lupus erythematosus (SLE) is characterized by the unpredictable occurrence of disease flares and organ damage. Attempts to stratify lupus patients have been limited to classification based on clinical information, leading to unsuccessful clinical trials and controversial research results. This study was undertaken to develop and validate a robust method to stratify patients with lupus according to longitudinal disease activity and whole-genome gene expression data in order to establish subgroups of patients who share disease progression mechanisms. METHODS: We used a cluster-based approach to stratify SLE patients based on the correlation between disease activity scores and longitudinal gene expression information. Clustering robustness was evaluated by the bootstrap method, and the clusters were characterized in terms of clinical and functional features. RESULTS: We observed a clear partition into 3 different disease clusters in 2 independent sets of patients, one pediatric and one adult, which was not influenced by treatment, race, or other source of bias. Two of the clusters differentiated into a group showing a correlation between the percentage of neutrophils and disease activity progression and a group showing a correlation between the percentage of lymphocytes and disease activity progression. The third cluster, in which the percentage of neutrophils correlated to a lesser degree with disease activity, was functionally more heterogeneous. Patients in the neutrophil-driven clusters had an increased risk of developing proliferative nephritis. CONCLUSION: Our findings indicate that SLE patients can be stratified into 3 subgroups of patients who show different mechanisms of disease progression and are clinically differentiated. Our results have important implications for treatment options, the design of clinical trials, our understanding of the etiology of the disease, and the prediction of severe glomerulonephritis.


Assuntos
Perfilação da Expressão Gênica , Lúpus Eritematoso Sistêmico/classificação , Lúpus Eritematoso Sistêmico/genética , Linfócitos/metabolismo , Neutrófilos/metabolismo , Adulto , Criança , Análise por Conglomerados , Progressão da Doença , Feminino , Glomerulonefrite/genética , Humanos , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/sangue , Nefrite Lúpica/genética , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Índice de Gravidade de Doença
15.
Rheumatology (Oxford) ; 57(8): 1350-1357, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29672737

RESUMO

Objectives: aPL are frequently present in SLE. In a well characterized SLE cohort we aimed at investigating the prevalence of aPL and assessing their analytical performance and clinical association by testing criteria specificities including LA, aCL IgG and IgM, anti-ß2-glycoprotein 1 (antiß2GP1) IgG and IgM, as well as the non-criteria aPS-PT IgG and IgM and anti-ß2GP1 domain 1 (aD1) IgG. Methods: We included 178 patients satisfying the ACR SLE classification criteria, from whom 283 samples and thrombotic events were collected longitudinally. Each sample was tested for criteria and non-criteria aPL using validated techniques in a single centre. Results: All assays provided highly reproducible results. Of the samples, 42.5% were positive for at least one criteria assay, 20.5% showed double positivity and 12.6% triple positivity. All criteria and non-criteria specificities persisted over time. Most antibody titres were only moderately correlated; however, strong correlation was observed on one hand between aD1 IgG, antiß2GP1 IgG and aCL IgG, and on the other between aPS-PT IgG and LA. aD1 IgG titres were extremely elevated in triple-positive samples. aPS-PT IgG by itself, and jointly with LA, was associated with thrombosis, an association mostly driven by venous thrombotic events. Conclusions: In this SLE cohort, the non-criteria aPL aD1 IgG and aPS-PT IgG performed differently. aD1 IgG was highly enriched in triple-positive samples, and aPS-PT IgG, jointly with LA, was associated with thrombotic events.


Assuntos
Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/etnologia , Lúpus Eritematoso Sistêmico/epidemiologia , Trombose/epidemiologia , Adolescente , Adulto , Idoso , Síndrome Antifosfolipídica/classificação , Síndrome Antifosfolipídica/imunologia , Criança , Feminino , Seguimentos , Humanos , Lúpus Eritematoso Sistêmico/classificação , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Suíça/epidemiologia , Trombose/imunologia , Fatores de Tempo , Adulto Jovem
16.
Clin Rheumatol ; 37(3): 817-818, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29392510

RESUMO

The American College of Rheumatology (ACR) classification criteria for lupus and Systemic Lupus International Collaborating Clinics (SLICC) criteria are designed to classify disease. However, they have become widely used as diagnostic criteria in clinical situations. Patients may be labelled as systemic lupus erythematosus (SLE) in their medical records, when in fact they have cutaneous lupus erythematosus (CLE) without systemic symptoms. We sought to investigate how many of our cutaneous lupus patients attending a dermatology lupus clinic were mislabelled as either CLE or SLE using the ACR and SLICC criteria. Thirty-six patients with biopsy-proven cutaneous lupus were identified. Fourteen (39%) of the patients were labelled as 'SLE' in their medical notes, either by dermatology or another medical team. Of these 14 patients, 12 (86%) fulfilled the ACR and SLICC criteria; however, two (14%) did not meet the criteria for SLE. Of the remaining 22 patients who were not labelled as having SLE, four (18%) met both the SLICC and ACR criteria, one (5%) met the ACR criteria and one (5%) met the SLICC criteria. These patients had a history of discoid or subacute lupus, with very few systemic symptoms. They met the criteria for SLE primarily on their cutaneous signs and positive serology. It is important to screen patients with CLE routinely for SLE. Although the ACR and SLICC criteria can be helpful as they have a high sensitivity for systemic lupus, their use needs to be paired with the clinical context and patient evolution. We found patients were labelled as SLE when in fact they had no evidence of systemic involvement, as well as patients labelled as cutaneous lupus who fulfilled the criteria for SLE, although unlikely having any systemic involvement. It is important to correctly identify patients as 'cutaneous lupus' or 'systemic lupus erythematosus' and documentation in clinical notes should be accurate to avoid confusion and allow appropriate treatment.


Assuntos
Lúpus Eritematoso Cutâneo/classificação , Lúpus Eritematoso Sistêmico/classificação , Reumatologia , Humanos , Lúpus Eritematoso Cutâneo/diagnóstico , Lúpus Eritematoso Sistêmico/diagnóstico , Índice de Gravidade de Doença , Avaliação de Sintomas
17.
Ann Pathol ; 38(1): 43-54, 2018 Feb.
Artigo em Francês | MEDLINE | ID: mdl-29290386

RESUMO

Lupus can present itself in a multitude of clinical and histopathological manifestations. Cutaneous lesions can be very variable either from the clinical point of view or at the microscopic scale. Signs can be specific, concerning the dermo-epidermal stage, the dermal stage or the hypodermal stage. Conversely, some manifestations can be not specific but associated to the lupus. Finally, the question of the differential diagnosis can be tricky and often requires a beam of clinical, biological and histopathological arguments.


Assuntos
Imunidade Celular , Lúpus Eritematoso Cutâneo/patologia , Lúpus Eritematoso Sistêmico/patologia , Autoanticorpos/imunologia , Autoantígenos/imunologia , Doenças do Tecido Conjuntivo/imunologia , Doenças do Tecido Conjuntivo/patologia , Diagnóstico Diferencial , Técnica Direta de Fluorescência para Anticorpo , Humanos , Lúpus Eritematoso Cutâneo/classificação , Lúpus Eritematoso Cutâneo/diagnóstico , Lúpus Eritematoso Cutâneo/imunologia , Lúpus Eritematoso Sistêmico/classificação , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Mucinoses/patologia , Dermatopatias/diagnóstico
18.
Autoimmun Rev ; 17(3): 316-322, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29366725

RESUMO

OBJECTIVE: To evaluate the performance in classifying systemic lupus erythematosus by the 2012 Systemic Lupus International Collaborating Clinics criteria (SLICC'12), versus the revised American College of Rheumatology criteria from 1997 (ACR'97) in adult and juvenile SLE patients. METHODS: A systematic literature search was conducted in PubMed and Embase for studies comparing SLICC'12 and ACR'97 with clinical diagnosis. A meta-analysis was performed to estimate the sensitivity and specificity of SLICC'12 and ACR'97. To assess classification earlier in the disease by either set, sensitivity and specificity were compared for patients with disease duration <5years. Sensitivity and specificity of individual criteria items were also assessed. RESULTS: In adult SLE (nine studies: 5236 patients, 1313 controls), SLICC'12 has higher sensitivity (94.6% vs. 89.6%) and similar specificity (95.5% vs. 98.1%) compared to ACR'97. For juvenile SLE (four studies: 568 patients, 339 controls), SLICC'12 demonstrates higher sensitivity (99.9% vs. 84.3%) than ACR'97, but much lower specificity (82.0% vs. 94.1%). SLICC'12 classifies juvenile SLE patients earlier in disease course. Individual items contributing to diagnostic accuracy are low complement, anti-ds DNA and acute cutaneous lupus in SLICC'12, and the immunologic and hematologic disorder in ACR'97. CONCLUSION: Based on sensitivity and specificity SLICC'12 is best for adult SLE. Following the view that higher specificity, i.e. avoidance of false positives, is preferable, ACR'97 is best for juvenile SLE even if associated with lower sensitivity. Our results on the contribution of the individual items of SLICC'12 and ACR´97 may be of value in future efforts to update classification criteria.


Assuntos
Lúpus Eritematoso Sistêmico/classificação , Reumatologia/classificação , Adolescente , Adulto , Criança , Progressão da Doença , Feminino , História do Século XX , História do Século XXI , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Estados Unidos , Adulto Jovem
19.
Arthritis Care Res (Hoboken) ; 70(3): 428-438, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28544593

RESUMO

OBJECTIVE: To review the published literature on the performance of indirect immunofluorescence (IIF)-HEp-2 antinuclear antibody (ANA) testing for classification of systemic lupus erythematosus (SLE). METHODS: A systematic literature search was conducted in the Medline, Embase, and Cochrane databases for articles published between January 1990 and October 2015. The research question was structured according to Population, Intervention, Comparator, Outcome (PICO) format rules, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations were followed where appropriate. Meta-regression analysis for diagnostic tests was performed, using the ANA titer as independent variable, while sensitivity and specificity were dependent variables. RESULTS: Of 4,483 publications screened, 62 matched the eligibility criteria, and another 2 articles were identified through reference analysis. The included studies comprised 13,080 SLE patients in total, of whom 12,542 (95.9%) were reported to be IIF-ANA positive at various titers. For ANA at titers of 1:40, 1:80, 1:160, and 1:320, meta-regression gave sensitivity values of 98.4% (95% confidence interval [95% CI] 97.6-99.0%), 97.8% (95% CI 96.8-98.5%), 95.8% (95% CI 94.1-97.1%), and 86.0% (95% CI 77.0-91.9%), respectively. The corresponding specificities were 66.9% (95% CI 57.8-74.9%), 74.7% (95% CI 66.7-81.3%), 86.2% (95% CI 80.4-90.5%), and 96.6% (95% CI 93.9-98.1%), respectively. CONCLUSION: The results of this systematic literature review and meta-regression confirm that IIF-ANAs have high sensitivity for SLE. ANAs at a titer of 1:80 have sufficiently high sensitivity to be considered as an entry criterion for SLE classification criteria, i.e., formally test other classification criteria for SLE only if ANAs of at least 1:80 have been found.


Assuntos
Anticorpos Antinucleares/imunologia , Lúpus Eritematoso Sistêmico/diagnóstico , Testes Sorológicos , Anticorpos Antinucleares/sangue , Biomarcadores/sangue , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/classificação , Lúpus Eritematoso Sistêmico/imunologia , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes
20.
Lupus ; 27(4): 556-563, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28933234

RESUMO

Objective To compare damage and mortality, from inception up to 10-year follow-up, between SLE patients meeting at baseline the 1997 ACR criteria or only the 2012 SLICC classification criteria. Methods Patients fulfilling the ACR and/or the SLICC classification criteria for SLE were enrolled at inception and followed-up to 10 years at an academic lupus clinic. Damage was defined as SLICC Damage Index (SDI) score ≥1. We assessed with multivariate Cox models the damage and mortality outcomes, according to SLE classification status at inception, adjusting for potential baseline confounders. Results We recruited 192 patients (69.8% fulfilling at inception the ACR criteria and 30.2% only the SLICC criteria). During follow-up, 24.0% of patients accrued organ damage and 4.2% died. Patients meeting ACR criteria compared to those with SLICC criteria alone presented during follow-up with more cases of lupus nephritis (35.1% versus 13.8%, p < 0.01), but less thrombotic antiphospholipid syndrome (4.5% versus 17.2%, p < 0.01). The Cox models showed no significant differences in risk for damage [hazard ratio (HR) (95% CI) 0.991 (0.453-2.167)] or death [hazard ratio (HR) (95% CI) 0.694 (0.107-4.506)] between groups. Conclusion The SLE classification status at inception identified different patterns of clinical phenotype, but did not influence damage accrual or mortality up to 10-year follow-up.


Assuntos
Lúpus Eritematoso Sistêmico/mortalidade , Lúpus Eritematoso Sistêmico/patologia , Adulto , Distribuição de Qui-Quadrado , Progressão da Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Lúpus Eritematoso Sistêmico/classificação , Lúpus Eritematoso Sistêmico/terapia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fenótipo , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo
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