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1.
Scand J Rheumatol ; 52(2): 190-195, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35723613

RESUMO

OBJECTIVES: Patients with laboratory criteria for anti-phospholipid syndrome (APS) but presenting only 'non-criteria' clinical manifestations are scarcely characterized in the literature. We aimed to analyse a cohort of these patients regarding the most prevalent manifestations, antibody profile, and treatments, while establishing a comparison with definite APS patients. METHOD: A retrospective analysis was conducted of individuals fulfilling APS laboratory criteria assessed in two tertiary European hospitals between 2005 and 2020. Patients without clinical criteria but with non-criteria manifestations (termed 'clinical non-criteria') and age-/gender-matched controls were included. RESULTS: Altogether, 75 clinical non-criteria patients were analysed, with haematological (thrombocytopenia, haemolytic anaemia) and 'mild' neurological manifestations (white-matter lesions, migraine) as the most prevalent non-obstetric involvements. These patients displayed more thrombocytopenia [odds ratio (OR) = 3.6, 95% confidence interval (CI) 1.7-7.6; p = 0.001] than controls with APS, but severe manifestations, such as valvular heart disease (p < 0.001), livedoid vasculopathy, seizures, chorea, transverse myelitis, bone necrosis, and alveolar haemorrhage, occurred only in definite APS patients. Corticosteroids were required by 40% of patients with thrombocytopenia. Manifestations in anticoagulated patients included white-matter lesions, nephropathy, superficial vein thrombosis, amaurosis fugax, and livedoid vasculopathy. Suspicion of progression towards systemic lupus erythematosus (SLE) occurred in 19% of non-SLE individuals. CONCLUSION: 'Clinical non-criteria' patients displayed significant treatment use, predominantly haematological involvement, and less severe manifestations than definite APS controls. Some patients may additionally progress to future SLE. The impact of certain manifestations flags them as potential future contributors to classifying individuals as definite APS.


Assuntos
Síndrome Antifosfolipídica , Vasculopatia Livedoide , Lúpus Eritematoso Sistêmico , Trombocitopenia , Doenças Vasculares , Humanos , Síndrome Antifosfolipídica/diagnóstico , Estudos Retrospectivos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Trombocitopenia/diagnóstico , Trombocitopenia/etiologia
2.
Ann Rheum Dis ; 80(6): 775-781, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33568386

RESUMO

BACKGROUND/OBJECTIVES: The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 classification criteria for systemic lupus erythematosus system showed high specificity, while attaining also high sensitivity. We hereby analysed the performance of the individual criteria items and their contribution to the overall performance of the criteria. METHODS: We combined the EULAR/ACR derivation and validation cohorts for a total of 1197 systemic lupus erythematosus (SLE) and n=1074 non-SLE patients with a variety of conditions mimicking SLE, such as other autoimmune diseases, and calculated the sensitivity and specificity for antinuclear antibodies (ANA) and the 23 specific criteria items. We also tested performance omitting the EULAR/ACR criteria attribution rule, which defines that items are only counted if not more likely explained by a cause other than SLE. RESULTS: Positive ANA, the new entry criterion, was 99.5% sensitive, but only 19.4% specific, against a non-SLE population that included other inflammatory rheumatic, infectious, malignant and metabolic diseases. The specific criteria items were highly variable in sensitivity (from 0.42% for delirium and 1.84% for psychosis to 75.6% for antibodies to double-stranded DNA), but their specificity was uniformly high, with low C3 or C4 (83.0%) and leucopenia <4.000/mm³ (83.8%) at the lowest end. Unexplained fever was 95.3% specific in this cohort. Applying the attribution rule improved specificity, particularly for joint involvement. CONCLUSIONS: Changing the position of the highly sensitive, non-specific ANA to an entry criterion and the attribution rule resulted in a specificity of >80% for all items, explaining the higher overall specificity of the criteria set.


Assuntos
Lúpus Eritematoso Sistêmico , Doenças Reumáticas , Reumatologia , Anticorpos Antinucleares , Estudos de Coortes , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Doenças Reumáticas/diagnóstico , Reumatologia/métodos , Sensibilidade e Especificidade , Estados Unidos
3.
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
4.
Lupus ; 28(9): 1158-1166, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31299879

RESUMO

INTRODUCTION: Although extensively characterized in the outpatient setting, systemic lupus erythematosus (SLE) in the hospitalization wards is still scarcely portrayed, particularly in the perspective of its evolution over the years. METHODS: Retrospective analysis of SLE patients hospitalized in the Department of Autoimmune Diseases of a university hospital during a 20-year period (1995-2015), describing hospitalization characteristics, causes and predictors of outcome. RESULTS: A total of 814 hospitalizations concerning 339 patients were analysed. The main causes of admission were flare (40.2%), infection (19.2%), diagnostic procedures (18.8%) and thrombotic events (5.4%). Therapy with cyclophosphamide (odds ratio (OR) 1.908, p = 0.047) was associated with admission due to infection, while antimalarials displayed a protective effect (OR 0.649, p = 0.024). Nearly 3.9% of patients required admission to an intensive care unit, with associated antiphospholipid syndrome (OR 7.385, p = 0.04) standing as a predicting factor for this outcome. Readmission at 30 days occurred in 5.8% of patients, with thrombocytopenia (OR 6.007, p = 0.002) and renal involvement (OR 3.362, p = 0.032) featuring as predicting factors. Eight patients died, with antiphospholipid syndrome (OR 26.814, p = 0.02) and thrombocytopenia (OR 31.523, p = 0.01) being associated with mortality. There was no significant variation in patients' demographics or admission causes across the 20-year period, except for a decrease in admissions due to thrombotic and musculoskeletal causes. Recently, an increase in the use of mycophenolate mofetil and lower doses of glucocorticoids were noted. CONCLUSION: While demographics of SLE hospitalizations have not markedly changed over the past 20 years, changes in therapy patterns were observed. Thrombocytopenia, antiphospholipid syndrome and renal involvement featured as predictors of poor outcome.


Assuntos
Síndrome Antifosfolipídica/epidemiologia , Hospitalização/estatística & dados numéricos , Lúpus Eritematoso Sistêmico/terapia , Trombocitopenia/epidemiologia , Adulto , Síndrome Antifosfolipídica/etiologia , Ciclofosfamida/administração & dosagem , Feminino , Humanos , Imunossupressores/administração & dosagem , Lúpus Eritematoso Sistêmico/mortalidade , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente/estatística & dados numéricos , Estudos Retrospectivos , Espanha , Trombocitopenia/etiologia
5.
Scand J Rheumatol ; 48(6): 469-473, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31264525

RESUMO

Objective: To investigate the effectiveness and safety of belimumab in patients with active systemic lupus erythematosus (SLE) in a real-life setting.Methods: All SLE patients treated with belimumab in the Department of Autoimmune Diseases of the Hospital Clinic of Barcelona were retrospectively analysed. The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, clinical SLEDAI-2K, levels of anti-double-stranded DNA (anti-dsDNA) antibody, complement components C3 and C4, and 50% haemolytic complement activity (CH50) were recorded at baseline and at 6, 12, and 24 months. Adverse events were also collected.Results: Twenty-three patients (100% women) were enrolled in the study. The most frequent manifestations that led to belimumab use were arthritis (91%) and skin involvement (39%). Both SLEDAI-2K and clinical SLEDAI-2K improved over time at all time-points (p < 0.005). Complement levels increased and the values of anti-dsDNA antibody decreased during treatment. The mean dose of prednisone could be tapered at all time-points and achieved maximum and significant reduction at 24 months (10.4 ± 4.8 mg/day to 4.8 ± 2.1 mg/day; p < 0.0005). Belimumab was well tolerated and only six patients (26%) experienced adverse events, all of which were classified as infections (one urinary tract infection without bacterial detection in urine culture and five viral infections). No deaths, severe infusion reactions, or hypersensitivity reactions were noted.Conclusion: In our patients with SLE, belimumab decreased disease activity and allowed tapering of the daily glucocorticoid dose with a good safety profile.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Feminino , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Estudos Retrospectivos
6.
BJOG ; 126(5): 656-661, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30222236

RESUMO

OBJECTIVE: To evaluate the subsequent rate of thrombosis among women with obstetric antiphospholipid syndrome (Ob-APS) in a multicentre database of antiphospholipid antibody (aPL)-positive patients, and the clinical utility of the adjusted Global Antiphospholipid Syndrome Score (aGAPSS), a validated tool to assess the likelihood of developing new thrombosis, in this group of patients. DESIGN: Retrospective study. SETTING: The Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking Clinical Database and Repository. POPULATION: Women with Ob-APS. METHODS: Comparison of clinical and laboratory characteristics and measurement of aGAPSS in women with Ob-APS, with or without thrombosis, after initial pregnancy morbidity (PM). MAIN OUTCOME MEASURES: Risk factors for thrombosis and aGAPSS. RESULTS: Of 550 patients, 126 had Ob-APS; 74/126 (59%) presented with thrombosis, and 47 (63%) of these women developed thrombosis after initial PM, in a mean time of 7.6 ± 8.2 years (4.9/100 patient years). Younger age at diagnosis of Ob-APS, additional cardiovascular risk factors, superficial vein thrombosis, heart valve disease, and multiple aPL positivity increased the risk of first thrombosis after PM. Women with thrombosis after PM had a higher aGAPSS compared with women with Ob-APS alone [median 11.5 (4-16) versus 9 (4-13); P = 0.0089]. CONCLUSION: Based on a retrospective analysis of our multicentre aPL database, 63% of women with Ob-APS developed thrombosis after initial obstetric morbidity; additional thrombosis risk factors, selected clinical manifestations, and high-risk aPL profile increased the risk. Women with subsequent thrombosis after Ob-APS had a higher aGAPSS at entry to the registry. We believe that aGAPSS is a valid tool to improve risk stratification in aPL-positive women. TWEETABLE ABSTRACT: More than 60% of women with obstetric antiphospholipid syndrome had thrombosis after initial pregnancy morbidity.


Assuntos
Síndrome Antifosfolipídica/complicações , Complicações Cardiovasculares na Gravidez/imunologia , Trombose/imunologia , Adulto , Anticorpos Antifosfolipídeos/sangue , Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/sangue , Ensaios Clínicos como Assunto , Bases de Dados Factuais , Feminino , Humanos , Gravidez , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco
7.
Lupus ; 27(4): 637-646, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29073812

RESUMO

Background Information regarding urinary biomarkers in Mestizo and Afro-Latin-American patients is very limited. We investigated whether levels of urinary neutrophil gelatinase-associated lipocalin (NGAL), and monocyte chemoattractant protein 1 (MCP-1) are good biomarkers to differentiate patients with lupus nephritis among Latin-American systemic lupus erythematosus (SLE) patients. Methods SLE patients meeting the revised American College of Rheumatology classification criteria for SLE were recruited. Urinary levels of NGAL and MCP-1 were measured using a commercial ELISA kit. Serum anti-C1q antibodies were measured by ELISA. SLE activity was measured with the systemic lupus erythematosus disease activity index (SLEDAI). Mann-Whitney tests were used to compare data and Spearman's rank correlations were used to examine associations between continuous variables. In addition, receiver operating characteristic curves were performed. Results One hundred and twenty SLE patients were recruited (87% women) with a median age of 32.8 ± 12.1 years and median disease duration of 7.3 ± 6.9 years. Afro-Latin-Americans had a significantly higher prevalence of lupus nephritis and higher SLEDAI scores than Mestizos. The three biomarkers were significantly higher in patients with lupus nephritis than in patients without lupus nephritis. In addition, urinary NGAL and MCP-1 were significantly higher in patients with active lupus nephritis than in inactive lupus nephritis. Urinary NGAL levels were significantly higher in Afro-Latin-American patients. A receiver operating characteristic curve for urinary biomarkers for lupus nephritis in all SLE patients showed a good level of sensitivity and specificity. Conclusion In our cohort of SLE patients, we found that urinary NGAL and MCP-1 in addition to anti-C1q antibodies were useful biomarkers for the identification of renal involvement and discrimination of active lupus nephritis among patients with renal disease.


Assuntos
Quimiocina CCL2/urina , Lipocalina-2/urina , Lúpus Eritematoso Sistêmico/complicações , Nefrite Lúpica/urina , Adulto , Autoanticorpos/sangue , Biomarcadores/sangue , Biomarcadores/urina , População Negra , Colômbia/epidemiologia , Complemento C1q/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Indígenas Sul-Americanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/etnologia , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/etnologia , Nefrite Lúpica/etiologia , Masculino , Valor Preditivo dos Testes , Prevalência , Regulação para Cima , Urinálise/métodos , Adulto Jovem
8.
Lupus ; 27(14): 2181-2189, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30282560

RESUMO

The importance of the immunomodulatory effects of vitamin D has recently been associated with autoimmune and chronic inflammatory diseases. Vitamin D deficiency has been linked to the development of autoimmune conditions. Antiphospholipid syndrome is an autoimmune disease characterized by thrombotic events and obstetric complications in patients with antiphospholipid antibodies. Current data show that patients with antiphospholipid syndrome have a high prevalence of vitamin D deficiency even without classic risk factors. Several studies have suggested vitamin D may have anti-thrombotic functions. In antiphospholipid syndrome, low vitamin D serum levels have been associated with thrombotic manifestations, suggesting a possible protective role of vitamin D in antiphospholipid syndrome. This literature review presents current evidence on the haemostatic functions of vitamin D and their possible relationship with the clinical manifestations of antiphospholipid syndrome.


Assuntos
Síndrome Antifosfolipídica/complicações , Deficiência de Vitamina D/complicações , Vitamina D/metabolismo , Anticorpos Antifosfolipídeos/sangue , Anticoagulantes/uso terapêutico , Feminino , Humanos , Gravidez , Complicações Hematológicas na Gravidez/etiologia , Trombose/tratamento farmacológico , Trombose/etiologia , Deficiência de Vitamina D/tratamento farmacológico
9.
Ann Rheum Dis ; 76(3): 476-485, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27457513

RESUMO

OBJECTIVES: Develop recommendations for women's health issues and family planning in systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). METHODS: Systematic review of evidence followed by modified Delphi method to compile questions, elicit expert opinions and reach consensus. RESULTS: Family planning should be discussed as early as possible after diagnosis. Most women can have successful pregnancies and measures can be taken to reduce the risks of adverse maternal or fetal outcomes. Risk stratification includes disease activity, autoantibody profile, previous vascular and pregnancy morbidity, hypertension and the use of drugs (emphasis on benefits from hydroxychloroquine and antiplatelets/anticoagulants). Hormonal contraception and menopause replacement therapy can be used in patients with stable/inactive disease and low risk of thrombosis. Fertility preservation with gonadotropin-releasing hormone analogues should be considered prior to the use of alkylating agents. Assisted reproduction techniques can be safely used in patients with stable/inactive disease; patients with positive antiphospholipid antibodies/APS should receive anticoagulation and/or low-dose aspirin. Assessment of disease activity, renal function and serological markers is important for diagnosing disease flares and monitoring for obstetrical adverse outcomes. Fetal monitoring includes Doppler ultrasonography and fetal biometry, particularly in the third trimester, to screen for placental insufficiency and small for gestational age fetuses. Screening for gynaecological malignancies is similar to the general population, with increased vigilance for cervical premalignant lesions if exposed to immunosuppressive drugs. Human papillomavirus immunisation can be used in women with stable/inactive disease. CONCLUSIONS: Recommendations for women's health issues in SLE and/or APS were developed using an evidence-based approach followed by expert consensus.


Assuntos
Síndrome Antifosfolipídica/tratamento farmacológico , Neoplasias dos Genitais Femininos/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Anticoncepcionais Orais Hormonais/uso terapêutico , Técnica Delphi , Detecção Precoce de Câncer , Terapia de Reposição de Estrogênios , Serviços de Planejamento Familiar , Feminino , Preservação da Fertilidade , Monitorização Fetal , Humanos , Menopausa , Cuidado Pré-Concepcional , Gravidez , Técnicas de Reprodução Assistida , Medição de Risco
10.
Lupus ; 26(9): 1002-1004, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27927881

RESUMO

Objective To illustrate an unusual case of Listeria cerebral abscess. Material and methods A 32-year-old pregnant woman with thrombotic antiphospholipid syndrome (APS) received corticotherapy for two weeks due to hemolysis, elevated liver enzymes, low platelet (HELLP) syndrome. After delivery she presented with neurological symptoms and fever. Results The MRI scan confirmed the presence of a brain abscess, and Listeria monocytogenes was isolated in blood cultures. After eight weeks of antibiotic treatment, the patient presented no sequelae. Conclusion L. monocytogenes should be included in the differential diagnosis of patients with fever and neurological dysfunction, especially in those with a recent history of corticotherapy.


Assuntos
Síndrome Antifosfolipídica/complicações , Abscesso Encefálico/complicações , Síndrome HELLP/diagnóstico , Listeria monocytogenes/isolamento & purificação , Complicações na Gravidez/microbiologia , Adulto , Abscesso Encefálico/diagnóstico por imagem , Abscesso Encefálico/tratamento farmacológico , Abscesso Encefálico/microbiologia , Diagnóstico Diferencial , Feminino , Febre/diagnóstico , Febre/etiologia , Síndrome HELLP/etiologia , Humanos , Listeriose/sangue , Listeriose/microbiologia , Imageamento por Ressonância Magnética , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/etiologia , Gravidez , Complicações na Gravidez/epidemiologia , Resultado do Tratamento
11.
Lupus ; 26(5): 510-516, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28394230

RESUMO

Objectives The objective of this study was to determine whether advanced MRI could provide biomarkers for diagnosis and prognosis in neuropsychiatric systemic lupus erythematosus (NPSLE). Methods Our prospective study included 28 systemic lupus erythematosus (SLE) patients with primary central NPSLE, 22 patients without NPSLE and 20 healthy controls. We used visual scales to evaluate atrophy and white matter hyperintensities, voxel-based morphometry and Freesurfer to measure brain volume, plus diffusion-tensor imaging (DTI) to assess white matter (WM) and gray matter (GM) damage. We compared the groups and correlated MRI abnormalities with clinical data. Results NPSLE patients had less GM and WM than controls ( p = 0.042) in the fronto-temporal regions and corpus callosum. They also had increased diffusivities in the temporal lobe WM ( p < 0.010) and reduced fractional anisotropy in the right frontal lobe WM ( p = 0.018). High clinical scores, longstanding disease, and low serum C3 were associated with atrophy, lower fractional anisotropy and higher diffusivity in the fronto-temporal lobes. Antimalarial treatment correlated negatively with atrophy in the frontal cortex and thalamus; it was also associated with lower diffusivity in the fronto-temporal WM clusters. Conclusions Atrophy and microstructural damage in fronto-temporal WM and GM in NPSLE correlate with severity, activity and the time from disease onset. Antimalarial treatment seems to give some brain-protective effects.


Assuntos
Substância Cinzenta/patologia , Lúpus Eritematoso Sistêmico/complicações , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Substância Branca/patologia , Adulto , Idoso , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Imagem de Tensor de Difusão/métodos , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Substância Branca/diagnóstico por imagem , Adulto Jovem
12.
Lupus ; 26(7): 675-681, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28059022

RESUMO

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) has been widely described in many studies conducted thus far. The syndrome incorporates five immune-mediated conditions, all associated with previous exposure to various agents such as vaccines, silicone implants and several others. The emergence of ASIA syndrome is associated with individual genetic predisposition, for instance those carrying HLA-DRB1*01 or HLA-DRB4 and results from exposure to external or endogenous factors triggering autoimmunity. Such factors have been demonstrated as able to induce autoimmunity in both animal models and humans via a variety of proposed mechanisms. In recent years, physicians have become more aware of the existence of ASIA syndrome and the relationship between adjuvants exposure and autoimmunity and more cases are being reported. Accordingly, we have created a registry that includes at present more than 300 ASIA syndrome cases that have been reported by different physicians worldwide, describing various autoimmune conditions induced by diverse adjuvants. In this review, we have summarized the updated literature on ASIA syndrome and the knowledge accumulated since 2013 in order to elucidate the association between the exposure to various adjuvant agents and its possible clinical manifestations. Furthermore, we especially referred to the relationship between ASIA syndrome and systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS).


Assuntos
Adjuvantes Imunológicos/efeitos adversos , Doenças Autoimunes/induzido quimicamente , Autoimunidade/imunologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Modelos Animais de Doenças , Predisposição Genética para Doença , Cadeias HLA-DRB1/genética , Cadeias HLA-DRB4/genética , Humanos , Síndrome
13.
Lupus ; 26(3): 266-276, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27510605

RESUMO

Objective A task force of scientists at the International Congress on Antiphospholipid Antibodies recognized that phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT) might contribute to a better identification of antiphospholipid syndrome (APS). Accordingly, initial and replication retrospective, cross-sectional multicentre studies were conducted to ascertain the value of aPS/PT for APS diagnosis. Methods In the initial study (eight centres, seven countries), clinical/laboratory data were retrospectively collected. Serum/plasma samples were tested for IgG aPS/PT at Inova Diagnostics (Inova) using two ELISA kits. A replication study (five centres, five countries) was carried out afterwards. Results In the initial study ( n = 247), a moderate agreement between the IgG aPS/PT Inova and MBL ELISA kits was observed ( k = 0.598). IgG aPS/PT were more prevalent in APS patients (51%) than in those without (9%), OR 10.8, 95% CI (4.0-29.3), p < 0.0001. Sensitivity, specificity, positive (LR+) and negative (LR-) likelihood ratio of IgG aPS/PT for APS diagnosis were 51%, 91%, 5.9 and 0.5, respectively. In the replication study ( n = 214), a moderate/substantial agreement between the IgG aPS/PT results obtained with both ELISA kits was observed ( k = 0.630). IgG aPS/PT were more prevalent in APS patients (47%) than in those without (12%), OR 6.4, 95% CI (2.6-16), p < 0.0001. Sensitivity, specificity, LR + and LR- for APS diagnosis were 47%, 88%, 3.9 and 0.6, respectively. Conclusions IgG aPS/PT detection is an easily performed laboratory parameter that might contribute to a better and more complete identification of patients with APS.


Assuntos
Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/diagnóstico , Lúpus Eritematoso Sistêmico/complicações , Fosfatidilserinas/imunologia , Complicações na Gravidez/diagnóstico , Trombose/diagnóstico , Adolescente , Adulto , Idoso , Síndrome Antifosfolipídica/sangue , Estudos Transversais , Feminino , Humanos , Cooperação Internacional , Masculino , Pessoa de Meia-Idade , Gravidez , Complicações na Gravidez/sangue , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
15.
Lupus ; 25(8): 864-72, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27252263

RESUMO

OBJECTIVE: Anti-double stranded desoxyribonucleic acid (anti-dsDNA) antibodies are considered fairly specific for systemic lupus erythematosus (SLE) and their quantification is useful for the clinical management of SLE patients. We assessed the diagnostic performance of the QUANTA Flash dsDNA chemiluminescent immunoassay (CIA) in comparison to an ELISA, using patients from five participating countries. The main focus was to evaluate the correlation between anti-dsDNA antibody results from the CIA and global SLE disease activity, as measured by the SLE Disease Activity Index 2000 (SLEDAI-2K). PATIENTS AND METHODS: A total of 1431 samples (SLE, n = 843; disease controls, n = 588) from five countries (Canada, USA, Portugal, Sweden and Spain) were tested with QUANTA Flash dsDNA (Inova Diagnostics, San Diego, CA, USA). Data obtained with the QUANTA Lite dsDNA SC ELISA (Inova Diagnostics) were available for samples from three sites (Canada, USA and Sweden, n = 566). The SLEDAI-2K scores were available for 805 SLE patients and a cut-off of > 4 was used to define active disease. RESULTS: QUANTA Flash dsDNA had a sensitivity of 54.3% for the diagnosis of SLE, combined with 89.8% specificity. Anti-dsDNA antibody levels were significantly higher (p < 0.0001) in active SLE (SLEDAI-2K > 4; n = 232; median value 83.0 IU/mL) versus the inactive patients (n = 573; median value 22.3 IU/mL), and the SLEDAI-2K scoring correlated with their dsDNA antibody levels (Spearman's rho = 0.44, p < 0.0001). Similar but less pronounced findings were also found for the ELISA, in relation to disease activity. CONCLUSIONS: The QUANTA Flash dsDNA assay showed good clinical performance in a large international multi-center study. Additionally, the strong correlation between anti-dsDNA antibody results and SLEDAI-2K scores supported the potential utility of QUANTA Flash dsDNA for monitoring disease activity.


Assuntos
Anticorpos Antinucleares/sangue , DNA/imunologia , Medições Luminescentes/métodos , Lúpus Eritematoso Sistêmico/imunologia , Adulto , Canadá , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Pessoa de Meia-Idade , Portugal , Sensibilidade e Especificidade , Espanha , Suécia , Estados Unidos
17.
Ann Rheum Dis ; 74(6): 1011-8, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24464962

RESUMO

OBJECTIVES: To assess the prevalence of the main causes of morbi-mortality in the antiphospholipid syndrome (APS) during a 10-year-follow-up period and to compare the frequency of early manifestations with those that appeared later. METHODS: In 1999, we started an observational study of 1000 APS patients from 13 European countries. All had medical histories documented when entered into the study and were followed prospectively during the ensuing 10 years. RESULTS: 53.1% of the patients had primary APS, 36.2% had APS associated with systemic lupus erythematosus and 10.7% APS associated with other diseases. Thrombotic events appeared in 166 (16.6%) patients during the first 5-year period and in 115 (14.4%) during the second 5-year period. The most common events were strokes, transient ischaemic attacks, deep vein thromboses and pulmonary embolism. 127 (15.5%) women became pregnant (188 pregnancies) and 72.9% of pregnancies succeeded in having one or more live births. The most common obstetric complication was early pregnancy loss (16.5% of the pregnancies). Intrauterine growth restriction (26.3% of the total live births) and prematurity (48.2%) were the most frequent fetal morbidities. 93 (9.3%) patients died and the most frequent causes of death were severe thrombosis (36.5%) and infections (26.9%). Nine (0.9%) cases of catastrophic APS occurred and 5 (55.6%) of them died. The survival probability at 10 years was 90.7%. CONCLUSIONS: Patients with APS still develop significant morbidity and mortality despite current treatment. It is imperative to increase the efforts in determining optimal prognostic markers and therapeutic measures to prevent these complications.


Assuntos
Síndrome Antifosfolipídica/mortalidade , Lúpus Eritematoso Sistêmico/mortalidade , Trombose/mortalidade , Aborto Espontâneo/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Epilepsia/etiologia , Feminino , Retardo do Crescimento Fetal/epidemiologia , Humanos , Lactente , Recém-Nascido , Infecções/etiologia , Infecções/mortalidade , Ataque Isquêmico Transitório/etiologia , Livedo Reticular/etiologia , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/complicações , Masculino , Pessoa de Meia-Idade , Gravidez , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Estudos Prospectivos , Embolia Pulmonar/etiologia , Embolia Pulmonar/mortalidade , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidade , Trombocitopenia/etiologia , Trombose/etiologia , Trombose Venosa/etiologia , Trombose Venosa/mortalidade , Adulto Jovem
18.
Lupus ; 24(6): 606-12, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25411259

RESUMO

Our objective was to evaluate whether vitamin D deficiency is associated with cervical human papilloma virus (HPV) infection in women with SLE. This is a cross-sectional study of 67 women with SLE. A structured questionnaire was administered to ascertain the possible risk factors associated with cervical HPV infection. A gynaecological evaluation and cervical cytology screening were made. HPV detection and genotyping was made by PCR and linear array assay. Serum 25 hydroxyvitamin D levels were quantified by chemiluminescence immunoassay. Mean age and disease duration were 44.8 ± 10.6 and 42.5 ± 11.8 years, respectively. Demographic characteristics were similar in patients with and without deficiency (<20 ng/ml and ≥20 ng/ml). There were 28.4% of women with cervical HPV infection and 68.4% had high-risk HPV infections. Patients with 25 hydroxyvitamin D levels <20 ng/ml had a higher prevalence of cervical HPV infection than those with levels ≥20 ng/ml (30.7% vs. 25.8%; p = 0.72). We found no significant difference when high-risk HPV infection was evaluated (36.8% vs. 31.5%; p = 0.73). In conclusion, women with SLE have a high prevalence of vitamin D deficiency and cervical HPV infection. However, we found no association between vitamin D deficiency and cervical HPV.


Assuntos
Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/virologia , Infecções por Papillomavirus/sangue , Doenças do Colo do Útero/sangue , Doenças do Colo do Útero/virologia , Vitamina D/análogos & derivados , Adulto , Estudos Transversais , Feminino , Genótipo , Humanos , Imunoensaio/métodos , Estudos Longitudinais , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Prevalência , Fatores de Risco , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal/métodos , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/virologia , Displasia do Colo do Útero/sangue , Displasia do Colo do Útero/virologia
19.
Lupus ; 24(1): 25-31, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25159099

RESUMO

BACKGROUND: Low bone mineral density (BMD) and vertebral fractures (VF) have been associated with atherosclerosis in the general population. We sought to investigate the relationship between BMD and VF and carotid atherosclerosis in women with systemic lupus erythematosus (SLE). METHODS: We studied 122 women with SLE. All patients had BMD, carotid intima-media thickness (IMT), and carotid artery atherosclerotic plaque assessment by ultrasound. RESULTS: Mean age at study entry was 44 years and mean disease duration was 11 years. Carotid plaque was found in 13 (11%) patients (9 postmenopausal and 4 premenopausal). Patients in the highest IMT quartile were more likely to be older (p = 0.001), have a higher body mass index (p = 0.008), and exhibit dyslipidemia at study entry (p = 0.041), compared with the lower three quartiles. BMD at the lumbar spine was lower in patients in the highest IMT quartile compared with the lower quartiles in the multivariate logistic analysis, however, there was no association between lumbar or total hip BMD and IMT (p = 0.91 and p = 0.6, respectively). IMT measurements did not differ according to the presence or absence of VF (0.08 ± 0.12 vs. 0.06 ± 0.03 mm, p = 0.11). A trend towards higher incidence of VF was found in patients with carotid plaque compared with those without (33% vs. 21%; p = 0.2). CONCLUSIONS: In patients with SLE, the presence of carotid atherosclerosis is not associated with low BMD or VF.


Assuntos
Densidade Óssea , Doenças das Artérias Carótidas/epidemiologia , Vértebras Lombares/lesões , Lúpus Eritematoso Sistêmico/epidemiologia , Osteoporose/epidemiologia , Fraturas da Coluna Vertebral/epidemiologia , Vértebras Torácicas/lesões , Acetábulo/fisiopatologia , Adulto , Índice de Massa Corporal , Doenças das Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Estudos Transversais , Dislipidemias/epidemiologia , Feminino , Cabeça do Fêmur/fisiopatologia , Humanos , Vértebras Lombares/fisiopatologia , Pessoa de Meia-Idade , Pós-Menopausa , Pré-Menopausa , Radiografia , Fatores de Risco , Fraturas da Coluna Vertebral/diagnóstico por imagem
20.
Neurologia ; 30(2): 83-9, 2015 Mar.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-24332784

RESUMO

INTRODUCTION: Migraine is a common and prevalent disease that contributes to health expenditure and interferes with quality of life. Our goal was to analyse the level of stress at work in a sample of migraine and its possible association with the chronicity of the process MATERIAL AND METHODS: We applied the Maslach Burnout Inventory, consisting of 22 items grouped into blocks that assess emotional exhaustion (EE), personal accomplishment (PA), depersonalisation at work (DP)] and positive influence (PI), to 94 consecutive subjects recruited in the outpatient clinic. Differences were compared between clinical groups (chronic migraine [CM]: > 15 days/month with headache over a 3-month period vs episodic migraine [EM]: < 15 days/month with headache) using the general linear model adjusted for age and MIDAS score RESULTS: The mean age was higher in the CM group. Mean MIDAS scores were 51 ± 4.1 in CM, and 17.7 ± 15 in EM (P=.001). Adjusted means for EE were 24.6 ± 2.6 in CM patients, 16.2 ± 2.6 in EM patients, and 13.4 ± 2.3 (P=.03) in the healthy group. MIDAS scale scores were inversely correlated to PA (P<.05) DISCUSSION: Our results suggest that the level of EE at work is higher in EM than in CM patients, while PA levels decrease as impact on the MIDAS scale increases. The Maslach scale is a potentially useful tool for studying migraine impact. Surprisingly, EE is higher in patients with fewer episodes; this tendency could be related to stress adaptation mechanisms present in patients with chronic illness.


Assuntos
Esgotamento Profissional/complicações , Emprego/psicologia , Transtornos de Enxaqueca/psicologia , Estresse Psicológico/complicações , Adulto , Doença Crônica , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/complicações , Qualidade de Vida
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