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1.
PLoS One ; 13(12): e0209343, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30586461

RESUMO

BACKGROUND: The TNFSF13B (TNF superfamily member 13b) gene encodes BAFF, a cytokine with a crucial role in the differentiation and activation of B cells. An insertion-deletion variant (GCTGT→A) of this gene, leading to increased levels of BAFF, has been recently implicated in the genetic predisposition to several autoimmune diseases, including multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis. Based on the elevated levels of this cytokine found in patients with giant cell arteritis (GCA) and systemic sclerosis (SSc), we aimed to assess whether this functional variant also represents a novel genetic risk factor for these two disorders. METHODS: A total of 1,728 biopsy-proven GCA patients from 4 European cohorts, 4,584 SSc patients from 3 European cohorts and 5,160 ethnically-matched healthy controls were included in the study. The single nucleotide polymorphism (SNP) rs374039502, which colocalizes with the genetic variant previously implicated in autoimmunity, was genotyped using a custom TaqMan assay. First, association analysis was conducted in each independent cohort using χ2 test in Plink (v1.9). Subsequently, different case/control sets were meta-analyzed by the inverse variance method. RESULTS: No statistically significant differences were found when allele distributions were compared between cases and controls for any of the analyzed cohorts. Similarly, combined analysis of the different sets evidenced a lack of association of the rs374039502 variant with GCA (P = 0.421; OR (95% CI) = 0.92 (0.75-1.13)) and SSc (P = 0.500; OR (95% CI) = 1.05 (0.91-1.22)). The stratified analysis considering the main clinical subphenotypes of these diseases yielded similar negative results. CONCLUSION: Our data suggest that the TNFSF13B functional variant does not contribute to the genetic network underlying GCA and SSc.


Assuntos
Fator Ativador de Células B/genética , Predisposição Genética para Doença , Arterite de Células Gigantes/genética , Escleroderma Sistêmico/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Estudos de Casos e Controles , Estudos de Coortes , Europa (Continente) , Feminino , Redes Reguladoras de Genes/genética , Técnicas de Genotipagem , Arterite de Células Gigantes/patologia , Humanos , Mutação INDEL , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Escleroderma Sistêmico/patologia
2.
Rheumatol Int ; 38(9): 1699-1704, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29946742

RESUMO

The efficacy of tocilizumab (TCZ), a monoclonal antibody to the interleukin (IL)-6 receptor, in suppressing disease activity in glucocorticoid-naïve patients with new-onset polymyalgia rheumatica (PMR) was studied. Its effect on a panel of cytokines and growth factors was evaluated. Three patients, fulfilling the PMR ACR/EULAR criteria, received TCZ at the dosage of 8 mg/kg every 4 weeks for three times followed by prednisone 0.2 mg/kg in case of inefficacy. Concentrations of IL-10, IL-6, tumour necrosis factor (TNF)-α, IL-1ß, IL-10, IL-17, interferon (IFN)-γ, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and leukaemia inhibitory factor (LIF) were measured at baseline, after 72 h of the first TCZ infusion and then at weeks 1, 4, 5, 8, 9, 12, 13, 14, 16, and 22. A slight clinical improvement was seen only after the first TCZ infusion, but was largely inferior to that of conventional doses of GC administered subsequently. An ischaemic visual accident suggestive of GCA occurred in one patient during TCZ treatment. IL-6 was increased at baseline compared to controls, further increased after the first TCZ infusion, and was suppressed by GC. IL-17 production decreased during TCZ treatment and reverted to pre-treatment levels after GC. VEGF e PDGF showed a less constant pattern, but an increase of VEGF concentration antedated visual symptoms. The other cytokines were not detectable in patients and controls. In our small sample, TCZ was not able to suppress inflammation at the same degree as GC. As a result, monotherapy with TCZ in PMR cannot be recommended, although its efficacy as adjunctive treatment in GC-resistant patients should be further evaluated.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Interleucina-6/antagonistas & inibidores , Interleucina-6/fisiologia , Polimialgia Reumática/imunologia , Idoso , Diabetes Mellitus Tipo 2 , Feminino , Humanos , Itália , Masculino , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Fator A de Crescimento do Endotélio Vascular
3.
Ann Rheum Dis ; 77(5): 636-643, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29358285

RESUMO

To develop evidence-based recommendations for the use of imaging modalities in primary large vessel vasculitis (LVV) including giant cell arteritis (GCA) and Takayasu arteritis (TAK). European League Against Rheumatism (EULAR) standardised operating procedures were followed. A systematic literature review was conducted to retrieve data on the role of imaging modalities including ultrasound, MRI, CT and [18F]-fluorodeoxyglucose positron emission tomography (PET) in LVV. Based on evidence and expert opinion, the task force consisting of 20 physicians, healthcare professionals and patients from 10 EULAR countries developed recommendations, with consensus obtained through voting. The final level of agreement was voted anonymously. A total of 12 recommendations have been formulated. The task force recommends an early imaging test in patients with suspected LVV, with ultrasound and MRI being the first choices in GCA and TAK, respectively. CT or PET may be used alternatively. In case the diagnosis is still in question after clinical examination and imaging, additional investigations including temporal artery biopsy and/or additional imaging are required. In patients with a suspected flare, imaging might help to better assess disease activity. The frequency and choice of imaging modalities for long-term monitoring of structural damage remains an individual decision; close monitoring for aortic aneurysms should be conducted in patients at risk for this complication. All imaging should be performed by a trained specialist using appropriate operational procedures and settings. These are the first EULAR recommendations providing up-to-date guidance for the role of imaging in the diagnosis and monitoring of patients with (suspected) LVV.


Assuntos
Arterite de Células Gigantes/diagnóstico por imagem , Imagem por Ressonância Magnética/normas , Reumatologia/normas , Arterite de Takayasu/diagnóstico por imagem , Ultrassonografia/normas , Vasculite/diagnóstico por imagem , Europa (Continente) , Fluordesoxiglucose F18 , Humanos , Imagem por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons/métodos , Tomografia por Emissão de Pósitrons/normas , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X/métodos , Tomografia Computadorizada por Raios X/normas , Ultrassonografia/métodos
5.
Clin Exp Rheumatol ; 36(1): 44-49, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28770709

RESUMO

OBJECTIVES: To evaluate if the timing of appearance with respect to disease onset may influence the arthritis presentation pattern in antisynthetase syndrome (ASSD). METHODS: The patients were selected from a retrospective large international cohort of ASSD patients regularly followed-up in centres referring to AENEAS collaborative group. Patients were eligible if they had an antisynthetase antibody testing positive in at least two determinations along with arthritis occurring either at ASSD onset (Group 1) or during the course of the disease (Group 2). RESULTS: 445 (70%; 334 females, 110 males, 1 transsexual) out of the 636 ASSD we collected had arthritis, in the majority of cases (367, 83%) from disease onset (Group 1). Patients belonging to Group 1 with respect to Group 2 had an arthritis more commonly polyarticular and symmetrical (p=0.015), IgM-Rheumatoid factor positive (p=0.035), erosions at hands and feet plain x-rays (p=0.036) and more commonly satisfying the 1987 revised classification criteria for rheumatoid arthritis (RA) (p=0.004). Features such as Raynaud's phenomenon, mechanic's hands and fever (e.g. accompanying findings) were more frequently reported in Group 2 (p=0.005). CONCLUSIONS: In ASSD, the timing of appearance with respect to disease onset influences arthritis characteristics. In particular, RA features are more common when arthritis occurs from ASSD onset, suggesting an overlap between RA and ASSD in these patients. When arthritis appears during the follow-up, it is very close to a connective tissue disease-related arthritis. Also, the different prevalence of accompanying features between these two groups is in line with this possibility.


Assuntos
Artrite/epidemiologia , Miosite/epidemiologia , Adulto , Artrite/diagnóstico , Artrite/imunologia , Autoanticorpos/sangue , Biomarcadores/sangue , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Miosite/diagnóstico , Miosite/imunologia , Fenótipo , Prevalência , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
6.
Am J Hum Genet ; 100(1): 64-74, 2017 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-28041642

RESUMO

Giant cell arteritis (GCA) is the most common form of vasculitis in individuals older than 50 years in Western countries. To shed light onto the genetic background influencing susceptibility for GCA, we performed a genome-wide association screening in a well-powered study cohort. After imputation, 1,844,133 genetic variants were analyzed in 2,134 case subjects and 9,125 unaffected individuals from ten independent populations of European ancestry. Our data confirmed HLA class II as the strongest associated region (independent signals: rs9268905, p = 1.94 × 10-54, per-allele OR = 1.79; and rs9275592, p = 1.14 × 10-40, OR = 2.08). Additionally, PLG and P4HA2 were identified as GCA risk genes at the genome-wide level of significance (rs4252134, p = 1.23 × 10-10, OR = 1.28; and rs128738, p = 4.60 × 10-9, OR = 1.32, respectively). Interestingly, we observed that the association peaks overlapped with different regulatory elements related to cell types and tissues involved in the pathophysiology of GCA. PLG and P4HA2 are involved in vascular remodelling and angiogenesis, suggesting a high relevance of these processes for the pathogenic mechanisms underlying this type of vasculitis.


Assuntos
Alelos , Predisposição Genética para Doença/genética , Variação Genética , Estudo de Associação Genômica Ampla , Arterite de Células Gigantes/genética , Plasminogênio/genética , Prolil Hidroxilases/genética , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Europa (Continente)/etnologia , Feminino , Humanos , Masculino , Neovascularização Fisiológica , Polimorfismo de Nucleotídeo Único/genética , Risco
7.
Arthritis Rheumatol ; 69(2): 429-438, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27748084

RESUMO

OBJECTIVE: To examine the performance of ultrasound (US) for the diagnosis of gout using the presence of monosodium urate monohydrate (MSU) crystals as the gold standard. METHODS: We analyzed data from the Study for Updated Gout Classification Criteria (SUGAR), a large, multicenter observational cross-sectional study of consecutive subjects with at least 1 swollen joint who conceivably may have gout. All subjects underwent arthrocentesis; cases were subjects with confirmed MSU crystals. Rheumatologists or radiologists who were blinded with regard to the results of the MSU crystal analysis performed US on 1 or more clinically affected joints. US findings of interest were double contour sign, tophus, and snowstorm appearance. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Multivariable logistic regression models were used to examine factors associated with positive US results among subjects with gout. RESULTS: US was performed in 824 subjects (416 cases and 408 controls). The sensitivity, specificity, PPV, and NPV for the presence of any 1 of the features were 76.9%, 84.3%, 83.3%, and 78.2%, respectively. Sensitivity was higher among subjects with a disease duration of ≥2 years and among subjects with subcutaneous nodules on examination (suspected tophus). Associations with a positive US finding included suspected clinical tophus (odds ratio [OR] 4.77 [95% confidence interval (95% CI) 2.23-10.21]), any abnormality on plain radiography (OR 4.68 [95% CI 2.68-8.17]), and serum urate level (OR 1.31 [95% CI 1.06-1.62]). CONCLUSION: US features of MSU crystal deposition had high specificity and high PPV but more limited sensitivity for early gout. The specificity remained high in subjects with early disease and without clinical signs of tophi.


Assuntos
Gota/sangue , Gota/diagnóstico por imagem , Ultrassonografia , Ácido Úrico/sangue , Estudos Transversais , Cristalização , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade
9.
Arthritis Care Res (Hoboken) ; 68(12): 1894-1898, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27014846

RESUMO

OBJECTIVE: To identify the best-performing survey definition of gout from items commonly available in epidemiologic studies. METHODS: Survey definitions of gout were identified from 34 epidemiologic studies contributing to the Global Urate Genetics Consortium (GUGC) genome-wide association study. Data from the Study for Updated Gout Classification Criteria (SUGAR) were randomly divided into development and test data sets. A data-driven case definition was formed using logistic regression in the development data set. This definition, along with definitions used in GUGC studies and the 2015 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) gout classification criteria were applied to the test data set, using monosodium urate crystal identification as the gold standard. RESULTS: For all tested GUGC definitions, the simple definition of "self-report of gout or urate-lowering therapy use" had the best test performance characteristics (sensitivity 82%, specificity 72%). The simple definition had similar performance to a SUGAR data-driven case definition with 5 weighted items: self-report, self-report of doctor diagnosis, colchicine use, urate-lowering therapy use, and hyperuricemia (sensitivity 87%, specificity 70%). Both of these definitions performed better than the 1977 American Rheumatism Association survey criteria (sensitivity 82%, specificity 67%). Of all tested definitions, the 2015 ACR/EULAR criteria had the best performance (sensitivity 92%, specificity 89%). CONCLUSION: A simple definition of "self-report of gout or urate-lowering therapy use" has the best test performance characteristics of existing definitions that use routinely available data. A more complex combination of features is more sensitive, but still lacks good specificity. If a more accurate case definition is required for a particular study, the 2015 ACR/EULAR gout classification criteria should be considered.


Assuntos
Estudos Epidemiológicos , Gota/classificação , Avaliação de Sintomas/métodos , Colchicina/uso terapêutico , Autoavaliação Diagnóstica , Feminino , Gota/urina , Supressores da Gota/uso terapêutico , Humanos , Hiperuricemia/classificação , Hiperuricemia/urina , Modelos Logísticos , Masculino , Sensibilidade e Especificidade , Ácido Úrico/urina
10.
Clin Exp Rheumatol ; 34(2): 254-60, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26886247

RESUMO

OBJECTIVES: To assess the diagnostic performance of ultrasound (US), x-rays, and microscopic analysis of synovial fluid (SF) for calcium pyrophosphate dihydrate crystal deposition disease (CPPD) using histology as a reference standard. METHODS: We enrolled consecutive patients with osteoarthritis waiting to undergo knee replacement surgery. Each patient underwent US of the knee, focusing on menisci and the hyaline cartilage, the day before surgery. During surgery, SF, menisci and condyles were retrieved and examined microscopically. For the meniscus and cartilage microscopic analysis, 8 samples were collected from each specimen and knee radiographs, performed up to 3 months before surgery, were also assessed. A dichotomous score was given for the presence/absence of CPP for each method. Microscopic findings of the specimens were considered the reference standard. All the procedures followed were in accordance with the ethical standards of the local responsible committee. RESULTS: 42 patients (14 males) were enrolled. All patients underwent US, 34 had eligible radiographs and 32 had SF analysis. 25 patients (59.5%) were positive for CPP at US, 15 (44.1%) at X-ray and 14 (43.7%) at SF. Sensitivity and specificity values were 96% and 87% for US, 75% and 93% for radiography and 77% and 100% for SF respectively. There were no statistically significant differences between the diagnostic performance across single tests. CONCLUSIONS: US proved to be at least as accurate as SF analysis for the diagnosis of CPPD. US, which is feasible and harmless, could be considered the first exam of choice for CPPD diagnosis.


Assuntos
Pirofosfato de Cálcio/análise , Condrocalcinose/diagnóstico , Líquido Sinovial/química , Idoso , Idoso de 80 Anos ou mais , Condrocalcinose/diagnóstico por imagem , Cristalização , Feminino , Humanos , Masculino , Radiografia , Sensibilidade e Especificidade , Ultrassonografia
11.
Arthritis Care Res (Hoboken) ; 68(10): 1530-7, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-26815286

RESUMO

OBJECTIVE: To develop a new composite disease activity score for gout and provide its first validation. METHODS: Disease activity has been defined as the ongoing presence of urate deposits that lead to acute arthritis and joint damage. Every measure for each Outcome Measures in Rheumatology core domain was considered. A 3-step approach (factor analysis, linear discriminant analysis, and linear regression) was applied to derive the Gout Activity Score (GAS). Decision to change treatment or 6-month flare count were used as the surrogate criteria of high disease activity. Baseline and 12-month followup data of 446 patients included in the Kick-Off of the Italian Network for Gout cohort were used. Construct- and criterion-related validity were tested. External validation on an independent sample is reported. RESULTS: Factor analysis identified 5 factors: patient-reported outcomes, joint examination, flares, tophi, and serum uric acid (sUA). Discriminant function analysis resulted in a correct classification of 79%. Linear regression analysis identified a first candidate GAS including 12-month flare count, sUA, visual analog scale (VAS) of pain, VAS global activity assessment, swollen and tender joint counts, and a cumulative measure of tophi. Alternative scores were also developed. The developed GAS demonstrated a good correlation with functional disability (criterion validity) and discrimination between patient- and physician-reported measures of active disease (construct validity). The results were reproduced in the external sample. CONCLUSION: This study developed and validated a composite measure of disease activity in gout. Further testing is required to confirm its generalizability, responsiveness, and usefulness in assisting with clinical decisions.


Assuntos
Progressão da Doença , Gota/diagnóstico , Índice de Gravidade de Doença , Idoso , Artralgia/etiologia , Artralgia/patologia , Análise Fatorial , Feminino , Seguimentos , Gota/tratamento farmacológico , Gota/patologia , Humanos , Articulações/patologia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Medição da Dor , Medidas de Resultados Relatados pelo Paciente , Análise de Regressão , Reprodutibilidade dos Testes , Ácido Úrico/sangue
12.
Clin Exp Rheumatol ; 34(1): 49-52, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26575013

RESUMO

OBJECTIVES: Ankylosis, or spontaneous bone fusion, of the small joints of the hand is a rare event in patients with rheumatoid arthritis (RA), being observed in 0.8% of them on conventional radiographs. It is associated with long-lasting and severe disease. In other settings, such as fracture healing, bone fusion is a reparative process. The aim of this paper is the study of the frequency of wrist ankylosis in patients with RA in comparison with other arthritides; to correlate ankylosis with disease activity. METHODS: A total of 94 patients affected by RA, 71 patients with different rheumatic conditions and 42 controls with no joint disease or with slight hand osteoarthritis were studied. DAS-28 CRP was calculated in patients with RA and psoriatic arthritis. MRI of the clinically most involved wrist was performed with a 0.2 T, extremity-dedicated MRI system. RESULTS: Of RA patients, 10/94 (10.6%) showed ankylosis in comparison with 2/113 (1.8%) controls (p=0.015). RA patients with ankylosis had longer disease duration (p=0.019) but similar disease activity. CONCLUSIONS: MRI-defined bone ankylosis is frequent in RA. It is not limited to seronegative spondyloarthritides and may be part of the bone damage observed in RA.


Assuntos
Anquilose/patologia , Artrite Reumatoide/patologia , Imagem por Ressonância Magnética , Articulação do Punho/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Progressão da Doença , Desenho de Equipamento , Feminino , Humanos , Imagem por Ressonância Magnética/instrumentação , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Índice de Gravidade de Doença
13.
Arthritis Care Res (Hoboken) ; 68(5): 667-72, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26414176

RESUMO

OBJECTIVE: To establish consensus for potential remission criteria to use in clinical trials of gout. METHODS: Experts (n = 88) in gout from multiple countries were invited to participate in a web-based questionnaire study. Three rounds of Delphi consensus exercises were conducted using SurveyMonkey, followed by a discrete-choice experiment using 1000Minds software. The exercises focused on identifying domains, definitions for each domain, and the timeframe over which remission should be defined. RESULTS: There were 49 respondents (56% response) to the initial survey, with subsequent response rates ranging from 57% to 90%. Consensus was reached for the inclusion of serum urate (98% agreement), flares (96%), tophi (92%), pain (83%), and patient global assessment of disease activity (93%) as measurement domains in remission criteria. Consensus was also reached for domain definitions, including serum urate (<0.36 mm), pain (<2 on a 10-point scale), and patient global assessment (<2 on a 10-point scale), all of which should be measured at least twice over a set time interval. Consensus was not achieved in the Delphi exercise for the timeframe for remission, with equal responses for 6 months (51%) and 1 year (49%). In the discrete-choice experiment, there was a preference towards 12 months as a timeframe for remission. CONCLUSION: These consensus exercises have identified domains and provisional definitions for gout remission criteria. Based on the results of these exercises, preliminary remission criteria are proposed with domains of serum urate, acute flares, tophus, pain, and patient global assessment. These preliminary criteria now require testing in clinical data sets.


Assuntos
Consenso , Gota/terapia , Índice de Gravidade de Doença , Avaliação de Sintomas/normas , Técnica Delfos , Gota/sangue , Gota/patologia , Humanos , Indução de Remissão , Inquéritos e Questionários , Fatores de Tempo , Ácido Úrico/sangue
14.
J Rheumatol Suppl ; 93: 53-6, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26523058

RESUMO

By providing additional and more sensitive information over clinical examination, imaging techniques are useful in the assessment of patients with psoriatic arthritis (PsA) and have been increasingly used to obtain additional clues to its pathogenesis. This review describes the current status and future development of conventional radiography, computed tomography, magnetic resonance imaging, positron emission tomography, and other novel techniques in the evaluation of PsA, with a focus on their use in diagnosing, monitoring, and predicting disease course and followup treatment response. The role and applications of ultrasonography are outside the scope and are reviewed elsewhere in these proceedings.


Assuntos
Artrite Psoriásica/diagnóstico , Diagnóstico por Imagem , Articulações , Artrografia , Diagnóstico por Imagem/métodos , Humanos , Articulações/diagnóstico por imagem , Articulações/patologia , Imagem por Ressonância Magnética , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Valor Preditivo dos Testes , Prognóstico , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
15.
Arthritis Care Res (Hoboken) ; 67(9): 1304-1315, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25777045

RESUMO

OBJECTIVE: To determine which clinical, laboratory, and imaging features most accurately distinguished gout from non-gout. METHODS: We performed a cross-sectional study of consecutive rheumatology clinic patients with ≥1 swollen joint or subcutaneous tophus. Gout was defined by synovial fluid or tophus aspirate microscopy by certified examiners in all patients. The sample was randomly divided into a model development (two-thirds) and test sample (one-third). Univariate and multivariate association between clinical features and monosodium urate-defined gout was determined using logistic regression modeling. Shrinkage of regression weights was performed to prevent overfitting of the final model. Latent class analysis was conducted to identify patterns of joint involvement. RESULTS: In total, 983 patients were included. Gout was present in 509 (52%). In the development sample (n = 653), the following features were selected for the final model: joint erythema (multivariate odds ratio [OR] 2.13), difficulty walking (multivariate OR 7.34), time to maximal pain <24 hours (multivariate OR 1.32), resolution by 2 weeks (multivariate OR 3.58), tophus (multivariate OR 7.29), first metatarsophalangeal (MTP1) joint ever involved (multivariate OR 2.30), location of currently tender joints in other foot/ankle (multivariate OR 2.28) or MTP1 joint (multivariate OR 2.82), serum urate level >6 mg/dl (0.36 mmoles/liter; multivariate OR 3.35), ultrasound double contour sign (multivariate OR 7.23), and radiograph erosion or cyst (multivariate OR 2.49). The final model performed adequately in the test set, with no evidence of misfit, high discrimination, and predictive ability. MTP1 joint involvement was the most common joint pattern (39.4%) in gout cases. CONCLUSION: Ten key discriminating features have been identified for further evaluation for new gout classification criteria. Ultrasound findings and degree of uricemia add discriminating value, and will significantly contribute to more accurate classification criteria.


Assuntos
Gota/classificação , Adulto , Idoso , Estudos Transversais , Feminino , Gota/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada
16.
Am J Hum Genet ; 96(4): 565-80, 2015 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-25817017

RESUMO

We conducted a large-scale genetic analysis on giant cell arteritis (GCA), a polygenic immune-mediated vasculitis. A case-control cohort, comprising 1,651 case subjects with GCA and 15,306 unrelated control subjects from six different countries of European ancestry, was genotyped by the Immunochip array. We also imputed HLA data with a previously validated imputation method to perform a more comprehensive analysis of this genomic region. The strongest association signals were observed in the HLA region, with rs477515 representing the highest peak (p = 4.05 × 10(-40), OR = 1.73). A multivariate model including class II amino acids of HLA-DRß1 and HLA-DQα1 and one class I amino acid of HLA-B explained most of the HLA association with GCA, consistent with previously reported associations of classical HLA alleles like HLA-DRB1(∗)04. An omnibus test on polymorphic amino acid positions highlighted DRß1 13 (p = 4.08 × 10(-43)) and HLA-DQα1 47 (p = 4.02 × 10(-46)), 56, and 76 (both p = 1.84 × 10(-45)) as relevant positions for disease susceptibility. Outside the HLA region, the most significant loci included PTPN22 (rs2476601, p = 1.73 × 10(-6), OR = 1.38), LRRC32 (rs10160518, p = 4.39 × 10(-6), OR = 1.20), and REL (rs115674477, p = 1.10 × 10(-5), OR = 1.63). Our study provides evidence of a strong contribution of HLA class I and II molecules to susceptibility to GCA. In the non-HLA region, we confirmed a key role for the functional PTPN22 rs2476601 variant and proposed other putative risk loci for GCA involved in Th1, Th17, and Treg cell function.


Assuntos
Genes MHC da Classe II/genética , Arterite de Células Gigantes/genética , Herança Multifatorial/genética , Estudos de Coortes , Grupo com Ancestrais do Continente Europeu/genética , Estudos de Associação Genética , Genótipo , Humanos , Análise Multivariada , Razão de Chances
17.
BMJ Open ; 5(1): e006029, 2015 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-25631308

RESUMO

OBJECTIVES: To develop and validate a new algorithm to identify patients with rheumatoid arthritis (RA) and estimate disease prevalence using administrative health databases (AHDs) of the Italian Lombardy region. DESIGN: Case-control and cohort diagnostic accuracy study. METHODS: In a randomly selected sample of 827 patients drawn from a tertiary rheumatology centre (training set), clinically validated diagnoses were linked to administrative data including diagnostic codes and drug prescriptions. An algorithm in steps of decreasing specificity was developed and its accuracy assessed calculating sensitivity/specificity, positive predictive value (PPV)/negative predictive value, with corresponding CIs. The algorithm was applied to two validating sets: 106 patients from a secondary rheumatology centre and 6087 participants from the primary care. Alternative algorithms were developed to increase PPV at population level. Crude and adjusted prevalence estimates taking into account algorithm misclassification rates were obtained for the Lombardy region. RESULTS: The algorithms included: RA certification by a rheumatologist, certification for other autoimmune diseases by specialists, RA code in the hospital discharge form, prescription of disease-modifying antirheumatic drugs and oral glucocorticoids. In the training set, a four-step algorithm identified clinically diagnosed RA cases with a sensitivity of 96.3 (95% CI 93.6 to 98.2) and a specificity of 90.3 (87.4 to 92.7). Both external validations showed highly consistent results. More specific algorithms achieved >80% PPV at the population level. The crude RA prevalence in Lombardy was 0.52%, and estimates adjusted for misclassification ranged from 0.31% (95% CI 0.14% to 0.42%) to 0.37% (0.25% to 0.47%). CONCLUSIONS: AHDs are valuable tools for the identification of RA cases at the population level, and allow estimation of disease prevalence and to select retrospective cohorts.


Assuntos
Algoritmos , Artrite Reumatoide/diagnóstico , Bases de Dados Factuais/estatística & dados numéricos , Sistemas Computadorizados de Registros Médicos/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/epidemiologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Itália/epidemiologia , Masculino , Registro Médico Coordenado , Pessoa de Meia-Idade , Prevalência , Reumatologia/estatística & dados numéricos , Sensibilidade e Especificidade
20.
Arthritis Res Ther ; 16(6): 492, 2014 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-25435011

RESUMO

INTRODUCTION: Polymyalgia rheumatica (PMR) is a common inflammatory disease in older people characterized by shoulder and/or pelvic girdle, and cervical and, occasionally, lumbar pain. Interspinous bursitis has been suggested as a potential cause of spinal symptoms. We evaluated, by 18 F-fluorodeoxyglucose (FDG) positron emission tomography integrated with computed tomography (PET/CT), the vertebral structures involved in PMR in a cohort of consecutive, untreated patients. METHODS: Sixty-five consecutive patients with PMR were studied. After a standardized physical examination, which included evaluation of pain and tenderness in the vertebral column, they underwent FDG-PET/CT. Sites of increased uptake and their correlation with spontaneous and provoked pain were recorded. For comparison, FDG-PET/CT was performed also in 65 age- and sex-matched controls and in 10 rheumatoid arthritis (RA) patients. RESULTS: The most frequent site of spontaneous and provoked pain was the cervical portion. FDG uptake was more frequent in the lumbar portion than at any other location, and in the cervical rather than in the thoracic portion (P <0.0001). No correlation was found between uptake and spontaneous or provoked pain. There was an association between presence of cervical and lumbar bursitis (r = 0.34, P = 0.007). None of the control patients and one out of ten RA patients showed interspinous bursitis. CONCLUSIONS: Interspinous bursitis is a frequent finding in the lumbar spine of patients with PMR. However, it is not associated with clinical symptoms and can hardly explain the spinal pain reported by the patients. Cervical pain is more frequent than lumbar pain in PMR patients and may be caused by shoulder girdle involvement.


Assuntos
Bursite/diagnóstico , Vértebras Cervicais/patologia , Dor Lombar/diagnóstico , Vértebras Lombares/patologia , Polimialgia Reumática/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Bursite/complicações , Estudos de Coortes , Feminino , Humanos , Dor Lombar/complicações , Masculino , Pessoa de Meia-Idade , Polimialgia Reumática/complicações , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada por Raios X/métodos
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