RESUMEN
This cross-sectional study evaluated the usefulness of an ultrasound technique in assessment of nail changes in 35 patients with psoriatic onychopathy and 25 with nail dystrophy secondary to onychomycosis. All patients underwent 3 examinations: a complete clinical assessment; a nail ultrasound study; and fungal culture. Nails of patients with psoriatic onychopathy presented a thinner nail plate and nail bed, measured by ultrasound, than did those with onychomycosis. The percentage of patients with a power Doppler signal ?2 at nail bed was significantly higher in psoriatic onychopathy than in onychomycosis, and structural bone lesions were more frequent in psoriatic onychopathy than in onychomycosis. These results suggest that the presence of structural damage and high-power Doppler signal are the main ultrasound findings supporting a diagnosis of psoriatic onychopathy.
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Enfermedades de la Uña/diagnóstico por imagen , Uñas/diagnóstico por imagen , Onicomicosis/diagnóstico por imagen , Psoriasis/diagnóstico por imagen , Ultrasonografía Doppler , Adulto , Estudios Transversales , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las PruebasRESUMEN
OBJECTIVE: To develop evidence-based recommendations on the use of ultrasound (US) and magnetic resonance imaging in patients with spondyloarthritis, including psoriatic arthritis, and juvenile idiopathic arthritis. METHODS: Recommendations were generated following a nominal group technique. A panel of experts (15 rheumatologists and 3 radiologists) was established in the first panel meeting to define the scope and purpose of the consensus document, as well as chapters, potential recommendations and systematic literature reviews (we used and updated those from previous EULAR documents). A first draft of recommendations and text was generated. Then, an electronic Delphi process (2 rounds) was carried out. Recommendations were voted from 1 (total disagreement) to 10 (total agreement). We defined agreement if at least 70% of participants voted≥7. The level of evidence and grade or recommendation was assessed using the Oxford Centre for Evidence Based Medicine levels of evidence. The full text was circulated and reviewed by the panel. The consensus was coordinated by an expert methodologist. RESULTS: A total of 12 recommendations were proposed for each disease. They include, along with explanations of the validity of US and magnetic resonance imaging regarding inflammation and damage detection, diagnosis, prediction (structural damage progression, flare, treatment response, etc.), monitoring and the use of US guided injections/biopsies. CONCLUSIONS: These recommendations will help clinicians use US and magnetic resonance imaging in patients with spondyloarthritis and juvenile idiopathic arthritis.
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Artritis Juvenil/diagnóstico por imagen , Artritis Psoriásica/diagnóstico por imagen , Imagen por Resonancia Magnética , Espondiloartritis/diagnóstico por imagen , Humanos , UltrasonografíaRESUMEN
OBJECTIVE: To develop evidence-based recommendations on the use of ultrasound (US) and magnetic resonance imaging (MRI) in patients with rheumatoid arthritis (RA). METHODS: Recommendations were generated following a nominal group technique. A panel of experts, consisting of 15 rheumatologists and 3 radiologists, was established in the first panel meeting to define the scope and purpose of the consensus document, as well as chapters, potential recommendations and systematic literature reviews (we used and updated those from previous EULAR documents). A first draft of recommendations and text was generated. Then, an electronic Delphi process (2 rounds) was carried out. Recommendations were voted from 1 (total disagreement) to 10 (total agreement). We defined agreement if at least 70% of experts voted ≥7. The level of evidence and grade or recommendation was assessed using the Oxford Centre for Evidence-based Medicine Levels of Evidence. The full text was circulated and reviewed by the panel. The consensus was coordinated by an expert methodologist. RESULTS: A total of 20 recommendations were proposed. They include the validity of US and MRI regarding inflammation and damage detection, diagnosis, prediction (structural damage progression, flare, treatment response, etc.), monitoring and the use of US guided injections/biopsies. CONCLUSIONS: These recommendations will help clinicians use US and MRI in RA patients.
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Artritis Reumatoide/diagnóstico por imagen , Imagen por Resonancia Magnética , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Técnica Delphi , Monitoreo de Drogas , Medicina Basada en la Evidencia , Humanos , UltrasonografíaRESUMEN
OBJECTIVE: To determine the level of residual inflammation [synovitis, bone marrow edema (BME), tenosynovitis, and total inflammation] quantified by hand magnetic resonance imaging (h-MRI) in patients with rheumatoid arthritis (RA) in remission according to 3 different definitions of clinical remission, and to compare these remission definitions. METHODS: A cross-sectional study. To assess the level of residual MRI inflammation in remission, cutoff levels associated to remission and median scores of MRI residual inflammatory lesions were calculated. Data from an MRI register of patients with RA who have various levels of disease activity were used. These were used for the analyses: synovitis, BME according to the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring system, tenosynovitis, total inflammation, and disease activity composite measures recorded at the time of MRI. Receiver-operating characteristic analysis was used to identify the best cutoffs associated with remission for each inflammatory lesion on h-MRI. Median values of each inflammatory lesion for each definition of remission were also calculated. RESULTS: A total of 388 h-MRI sets of patients with RA with different levels of disease activity, 130 in remission, were included. Cutoff values associated with remission according to the Simplified Disease Activity Index (SDAI) ≤ 3.3 and the Boolean American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) definitions for BME and tenosynovitis (1 and 3, respectively) were lower than BME and tenosynovitis (2 and 5, respectively) for the Disease Activity Score on 28 joints (DAS28) ≤ 2.6. Median scores for synovitis, BME, and total inflammation were also lower for the SDAI and Boolean ACR/EULAR remission criteria compared with DAS28. CONCLUSION: Patients with RA in remission according to the SDAI and Boolean ACR/EULAR definitions showed lower levels of MRI-detected residual inflammation compared with DAS28.
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Artritis Reumatoide/diagnóstico por imagen , Articulaciones de la Mano/diagnóstico por imagen , Sinovitis/diagnóstico por imagen , Tenosinovitis/diagnóstico por imagen , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Estudios Transversales , Progresión de la Enfermedad , Humanos , Inflamación/diagnóstico por imagen , Imagen por Resonancia Magnética , Inducción de Remisión , Índice de Severidad de la Enfermedad , Sinovitis/tratamiento farmacológico , Tenosinovitis/tratamiento farmacológico , Resultado del TratamientoRESUMEN
OBJECTIVE: RA patients with serum ACPA have a strong and specific genetic background. The objective of the study was to identify new susceptibility genes for ACPA-positive RA using a genome-wide association approach. METHODS: A total of 924 ACPA-positive RA patients with joint damage in hands and/or feet, and 1524 healthy controls were genotyped in 582 591 single-nucleotide polymorphisms (SNPs) in the discovery phase. In the validation phase, the most significant SNPs in the genome-wide association study representing new candidate loci for RA were tested in an independent cohort of 863 ACPA-positive patients with joint damage and 1152 healthy controls. All individuals from the discovery and validation cohorts were Caucasian and of Southern European ancestry. RESULTS: In the discovery phase, 60 loci not previously associated with RA risk showed evidence for association at P < 5×10(-4) and were tested for replication in the validation cohort. A total of 12 loci were replicated at the nominal level (P < 0.05, same direction of effect as in the discovery phase). When combining the discovery and validation cohorts, an intronic SNP in the Solute Carrier family 8 gene (SLC8A3) was found to be associated with ACPA-positive RA at a genome-wide level of significance RA [odds ratio (95% CI): 1.42 (1.25, 1.6), Pcombined = 3.19×10(-8)]. CONCLUSIONS: SLC8A3 was identified as a new risk locus for ACPA-positive RA. This study demonstrates the advantage of analysing relevant subsets of RA patients to identify new genetic risk variants.
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Artritis Reumatoide/genética , Autoanticuerpos/sangre , Sitios Genéticos , Predisposición Genética a la Enfermedad , Intercambiador de Sodio-Calcio/genética , Adulto , Artritis Reumatoide/sangre , Artritis Reumatoide/inmunología , Autoanticuerpos/inmunología , Estudios de Casos y Controles , Femenino , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Péptidos Cíclicos/inmunología , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Intercambiador de Sodio-Calcio/sangre , Población Blanca/genéticaRESUMEN
OBJECTIVE: Rheumatoid factor (RF) is a well-established diagnostic and prognostic biomarker in rheumatoid arthritis (RA). However, â¼20% of RA patients are negative for this anti-IgG antibody. To date, only variation at the HLA-DRB1 gene has been associated with the presence of RF. This study was undertaken to identify additional genetic variants associated with RF positivity. METHODS: A genome-wide association study (GWAS) for RF positivity was performed using an Illumina Quad610 genotyping platform. A total of 937 RF-positive and 323 RF-negative RA patients were genotyped for >550,000 single-nucleotide polymorphisms (SNPs). Association testing was performed using an allelic chi-square test implemented in Plink software. An independent cohort of 472 RF-positive and 190 RF-negative RA patients was used to validate the most significant findings. RESULTS: In the discovery stage, a SNP in the IRX1 locus on chromosome 5p15.3 (SNP rs1502644) showed a genome-wide significant association with RF positivity (P = 4.13 × 10(-8) , odds ratio [OR] 0.37 [95% confidence interval (95% CI) 0.26-0.53]). In the validation stage, the association of IRX1 with RF was replicated in an independent group of RA patients (P = 0.034, OR 0.58 [95% CI 0.35-0.97] and combined P = 1.14 × 10(-8) , OR 0.43 [95% CI 0.32-0.58]). CONCLUSION: To our knowledge, this is the first GWAS of RF positivity in RA. Variation at the IRX1 locus on chromosome 5p15.3 is associated with the presence of RF. Our findings indicate that IRX1 and HLA-DRB1 are the strongest genetic factors for RF production in RA.
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Artritis Reumatoide/genética , Sitios Genéticos , Proteínas de Homeodominio/genética , Factor Reumatoide/genética , Factores de Transcripción/genética , Variación Genética , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Polimorfismo de Nucleótido Simple , RiesgoRESUMEN
The aim of the study was to assess drug levels, immunogenicity and sacroiliitis on MRI in patients with axial spondyloarthritis under biologic tapering strategy. Consecutive patients with axial spondyloarthritis who remained in low disease activity more than 1 year after dose tapering of infliximab and adalimumab were included. Plasma drug concentrations of TNF inhibitors and anti-drug antibodies were determined, and MRI of sacroiliac joints was evaluated. Of twenty patients included, eighteen had therapeutic drug levels, no patient had anti-drug antibodies, and no patient had active sacroiliitis on MRI. These data could support the biologic tapering strategy and their maintenance over time.
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Adalimumab/administración & dosificación , Anticuerpos/sangre , Productos Biológicos/administración & dosificación , Infliximab/administración & dosificación , Articulación Sacroiliaca/efectos de los fármacos , Sacroileítis/tratamiento farmacológico , Espondiloartritis/tratamiento farmacológico , Adalimumab/sangre , Adalimumab/inmunología , Adulto , Productos Biológicos/sangre , Estudios Transversales , Esquema de Medicación , Monitoreo de Drogas , Femenino , Humanos , Infliximab/sangre , Infliximab/inmunología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Articulación Sacroiliaca/diagnóstico por imagen , Sacroileítis/diagnóstico por imagen , Sacroileítis/inmunología , Espondiloartritis/diagnóstico por imagen , Espondiloartritis/inmunología , Factores de Tiempo , Resultado del TratamientoRESUMEN
INTRODUCTION: Interleukin-6 (IL-6) cytokine signaling is key in Rheumatoid Arthritis (RA) pathophysiology. Blocking IL-6 receptor (IL6R) has proven to be a highly effective treatment to prevent joint damage. This study was performed to investigate the association between the genetic variation at IL6R gene and the severity of joint damage in RA. METHODS: IL6R gene tagging SNPs (n = 5) were genotyped in a discovery group of 527 RA patients from 5 different university hospitals from Spain. For each marker, a linear regression analysis was performed using an additive model and adjusting for the years of evolution of the disease, autoantibody status, gender and age. Haplotypes combining the SNPs were also estimated and tested for association with the level of joint destruction. Using an independent cohort of 705 RA patients from 6 university hospitals we performed a validation study of the SNPs associated in the discovery phase. RESULTS: In the discovery group we found a highly significant association between IL6R SNP rs4845618 and the level of joint destruction in RA (P = 0.0058, P corrected = 0.026), and a moderate association with SNP rs4453032 (P = 0.02, P corrected = 0.05). The resulting haplotype from both SNPs was more significantly associated with joint damage (P = 0.0037, P corrected = 0.011). Using the validation cohort, we replicated the association between the two IL-6R SNPs with the degree of joint destruction in RA (P = 0.007 and P = 0.04, meta-analysis P = 0.00011 and P = 0.0021, respectively), and the haplotype association (P = 0.0058, meta-analysis P = 6.64 e-5). CONCLUSIONS: Genetic variation at IL6R gene is associated with joint damage in RA.
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Artritis Reumatoide/genética , Predisposición Genética a la Enfermedad/genética , Articulaciones/metabolismo , Polimorfismo de Nucleótido Simple , Receptores de Interleucina-6/genética , Alelos , Estudios de Cohortes , Frecuencia de los Genes , Genotipo , Haplotipos , Humanos , Articulaciones/patología , Modelos Lineales , Desequilibrio de Ligamiento , Metaanálisis como Asunto , EspañaRESUMEN
The aim of the study was to assess whether dose reduction of biological treatment in patients with axial spondyloarthritis in sustained remission could be effective to maintain remission or low disease activity at 1 year and to explore baseline differences between patients who remained in remission or low disease activity and patients who relapsed. This was a prospective, observational study. All consecutive patients with axial spondyloarthritis in sustained remission were included and received low doses of anti-TNF-α according to a dose reduction protocol. At 1 year, the percentage of patients in remission or low disease activity and in relapse and the differences in baseline characteristics between the two groups were calculated. Of forty-two patients, 76.2 % remained in remission or low disease activity at 1 year. A significant shorter duration of remission before dose reduction, shorter duration of biological treatment and shorter disease duration were observed in the relapse group. Most of our patients with axial spondyloarthritis remained in remission or low disease activity at 1 year after dosage reduction of biologics and shorter duration of remission, shorter duration of biological treatment and shorter disease duration discriminated the patients who relapsed.
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Antiinflamatorios/administración & dosificación , Productos Biológicos/administración & dosificación , Espondiloartritis/tratamiento farmacológico , Adulto , Antiinflamatorios/uso terapéutico , Productos Biológicos/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Recurrencia , Inducción de Remisión , Índice de Severidad de la Enfermedad , Espondiloartritis/diagnóstico , Resultado del TratamientoRESUMEN
OBJECTIVE: Anti-TNF therapies have been highly efficacious in the management of rheumatoid arthritis (RA), but 25-30% of patients do not show a significant clinical response. There is increasing evidence that genetic variation at the Fc receptor FCGR2A is associated with the response to anti-TNF therapy. We aimed to validate this genetic association in a patient cohort from the Spanish population, and also to identify new genes functionally related to FCGR2A that are also associated with anti-TNF response. METHODS: A total of 348 RA patients treated with an anti-TNF therapy were included and genotyped for FCGR2A polymorphism rs1081274. Response to therapy was determined at 12 weeks, and was tested for association globally and independently for each anti-TNF drug (infliximab, etanercept and adalimumab). Using gene expression profiles from macrophages obtained from synovial fluid of RA patients, we searched for genes highly correlated with FCGR2A expression. Tag SNPs were selected from each candidate gene and tested for association with the response to therapy. RESULTS: We found a significant association between FCGR2A and the response to adalimumab (P=0.022). Analyzing the subset of anti-CCP positive RA patients (78%), we also found a significant association between FCGR2A and the response to infliximab (P=0.035). DHX32 and RGS12 were the most consistently correlated genes with FCGR2A expression in RA synovial fluid macrophages (P<0.001). We found a significant association between the genetic variation at DHX32 (rs12356233, corrected P=0.019) and a nominally significant association between RGS12 and the response to adalimumab (rs4690093, uncorrected P=0.040). In the anti-CCP positive group of patients, we also found a nominally significant association between RGS12 and the response to infliximab (rs2857859, uncorrected P=0.042). CONCLUSIONS: In the present study we have validated the FCGR2A association in an independent population, and we have identified new genes associated with the response to anti-TNF therapy in RA.
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Antirreumáticos/farmacología , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Polimorfismo de Nucleótido Simple , Receptores de IgG/genética , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto , Antirreumáticos/uso terapéutico , Artritis Reumatoide/inmunología , Femenino , Humanos , Macrófagos/efectos de los fármacos , Masculino , Líquido Sinovial/efectos de los fármacos , Líquido Sinovial/inmunología , Resultado del TratamientoAsunto(s)
Antirreumáticos/efectos adversos , Terapia Biológica/efectos adversos , Predisposición Genética a la Enfermedad , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades de la Piel/inducido químicamente , Enfermedades de la Piel/genética , Adulto , Antirreumáticos/uso terapéutico , Proteínas Ricas en Prolina del Estrato Córneo/genética , Femenino , Marcadores Genéticos , Antígenos HLA/genética , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Enfermedades Reumáticas/genéticaRESUMEN
OBJECTIVE: To evaluate the association of synovitis, bone marrow edema (BME), and tenosynovitis in the progression of erosions quantified by hand magnetic resonance imaging (MRI) at 1 year in patients with early rheumatoid arthritis (RA) in remission. METHODS: A total of 56 of 196 patients with early RA in remission at 1 year and with available MRI data at baseline and at 12 months were included. MRI images were assessed according to the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) system. Persistent remission was defined as 28-joint Disease Activity Score-erythrocyte sedimentation rate ≤ 2.6 and/or Simplified Disease Activity Index ≤ 3.3 and/or the new boolean American College of Rheumatology/European League Against Rheumatism remission criteria for a continuous period of at least 6 months. Progression of bone erosions was defined as an increase of 1 or more units in annual RAMRIS score for erosions compared to baseline. RESULTS: At 1 year, the majority of patients with RA in sustained remission showed some inflammatory activity on MRI (94.6% synovitis, 46.4% BME, and 58.9% tenosynovitis) and 19 of the 56 patients (33.9%) showed MRI progression of bone erosions. A significant difference was observed in MRI BME at 1 year, with higher mean score in patients with progression compared to nonprogression of erosions (4.8 ± 5.6 and 1.4 ± 2.6, p = 0.03). CONCLUSION: Subclinical inflammation was identified by MRI in 96.4% of patients with RA in sustained clinical remission. Significantly higher scores of BME after sustained remission were observed in patients with progression of erosions compared to patients with no progression. The persistence of higher scores of BME may explain the progression of bone erosions in patients with persistent clinical remission.
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Artritis Reumatoide/tratamiento farmacológico , Enfermedades Óseas/patología , Progresión de la Enfermedad , Edema/patología , Mano , Imagen por Resonancia Magnética , Sinovitis/patología , Antirreumáticos/uso terapéutico , Artritis Reumatoide/complicaciones , Sedimentación Sanguínea , Enfermedades Óseas/diagnóstico , Evaluación de la Discapacidad , Edema/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Inducción de Remisión , Reproducibilidad de los Resultados , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Sinovitis/diagnóstico , Factores de Tiempo , Resultado del TratamientoAsunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Vértebras Cervicales/diagnóstico por imagen , Vértebras Lumbares/diagnóstico por imagen , Articulación Sacroiliaca/diagnóstico por imagen , Espondiloartritis/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adalimumab , Adulto , Anticuerpos Monoclonales Humanizados/uso terapéutico , Progresión de la Enfermedad , Etanercept , Femenino , Estudios de Seguimiento , Humanos , Inmunoglobulina G/uso terapéutico , Infliximab , Masculino , Radiografía , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Espondiloartritis/diagnóstico por imagen , Resultado del TratamientoAsunto(s)
Anticuerpos Monoclonales de Origen Murino/efectos adversos , Antirreumáticos/efectos adversos , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/fisiología , Hepatitis B/inducido químicamente , Replicación Viral/efectos de los fármacos , Anciano , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Humanos , Masculino , RituximabRESUMEN
The sacroiliac joints are involved in most cases of axial spondyloarthropathy, the first manifestation usually being sacroiliitis. A finding of sacroiliitis at radiography is the classic diagnostic hallmark of axial spondyloarthropathy. However, radiographic changes reflect structural damage rather than active inflammation, which may delay the diagnosis by several years. In the past decade, the field of spondyloarthropathy has undergone major changes, largely driven by the development of new drugs for the treatment of ankylosing spondylitis. In recent years, the Assessment of SpondyloArthritis international Society has focused on the reassessment of existing classification criteria and the development and validation of diagnostic tools to facilitate early diagnosis and assessment of treatment response. Magnetic resonance (MR) imaging is the most recent innovation and the important change with respect to the previously established classification criteria. This modality has become an integral part of managing patients with sacroiliitis. MR imaging can serve as a biomarker of disease activity, allows monitoring, and can provide guidance for the treatment of affected patients, and it will likely become even more central to the care of these patients. Familiarity with the anatomy, anatomic variants, and physiologic changes of the sacroiliac joints is important for correctly interpreting findings and avoiding misdiagnosis.
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Vértebra Cervical Axis/patología , Predicción , Imagen por Resonancia Magnética/tendencias , Sacroileítis/etiología , Sacroileítis/patología , Espondiloartropatías/complicaciones , Espondiloartropatías/patología , Adulto , Humanos , Imagen por Resonancia Magnética/normas , Masculino , Guías de Práctica Clínica como AsuntoRESUMEN
AIM: The present study was undertaken to replicate the association of candidate genes for anti-TNF response in rheumatoid arthritis. Candidate genes were selected from a recent genome-wide association study on anti-TNF response performed in a population from Denmark. MATERIALS & METHODS: Genomic DNA was obtained from 315 Spanish rheumatoid arthritis patients having received an anti-TNF agent as their first biological therapy. SNPs from NR2FR2, MAP2K6, CBLN2 and PDE3A-SLCO1C1 candidate loci were genotyped. RESULTS: The PDE3A-SLCO1C1 locus rs3794271 SNP showed a highly significant association with anti-TNF treatment response (p = 1.74 × 10â»5). Combining the statistical evidence from the Spanish and Danish rheumatoid arthritis cohorts, the associated rs3794271 SNP reached a genome-wide significance level of association (p = 3.3 × 10⻹°). CONCLUSION: The present findings establish the PDE3A-SLCO1C1 locus as a strong genetic marker of anti-TNF therapy response.
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Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 3/genética , Transportadores de Anión Orgánico/genética , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Antirreumáticos/uso terapéutico , Dinamarca , Femenino , Sitios Genéticos , Marcadores Genéticos/genética , Estudio de Asociación del Genoma Completo/métodos , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Resultado del TratamientoRESUMEN
OBJECTIVE: The LCE3C_LCE3B-del variant is associated with psoriasis and rheumatoid arthritis. Its role in psoriatic arthritis (PsA) is unclear, however, as shown by 3 recent studies with contradictory results. In order to investigate whether LCE3C_LCE3B-del constitutes a risk factor for PsA susceptibility, we first tested this variant in patients with PsA from Spanish and Italian populations and then performed a meta-analysis including the previous case-control studies. METHODS: We genotyped LCE3C_LCE3B-del and its tag single-nucleotide polymorphism (SNP), rs4112788, in an original discovery cohort of 424 Italian patients with PsA and 450 unaffected control subjects. A Spanish replication cohort consisting of 225 patients with PsA and 469 control subjects was also genotyped. A meta-analysis considering 7,758 control subjects and 2,325 patients with PsA was also performed. RESULTS: We observed a significant association between PsA and the LCE3C_LCE3B-del tag SNP in the Italian and Spanish cohorts, with an overall corrected P value of 0.00019 and a corresponding odds ratio of 1.35 (95% confidence interval 1.14-1.59). Stratified analyses by subphenotype indicated a stronger association for patients with oligoarticular disease. Meta-analysis including data from all previous published studies confirmed an association of PsA with the LCE3C_LCE3B-del tag SNP. CONCLUSION: LCE3C_LCE3B-del is a susceptibility factor for PsA, confirming the existence of a shared risk factor involving the epidermal skin barrier in autoimmune disorders.
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Artritis Psoriásica/genética , Proteínas Ricas en Prolina del Estrato Córneo/genética , Predisposición Genética a la Enfermedad , Adulto , Alelos , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Genotipo , Humanos , Italia , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , España , Población Blanca/genéticaRESUMEN
OBJECTIVE: To assess the efficacy of etanercept in reducing tenosynovitis evaluated by MRI of the hand (h-MRI) in patients with active rheumatoid arthritis (RA) refractory to disease-modifying antirheumatic drug (DMARD) after 6 weeks of treatment. METHODS: 31 patients with active RA defined by a disease activity score (DAS28) >3.2 and synovitis in the hands were randomised into two groups: 19 patients received 50 mg weekly subcutaneous etanercept added to previous DMARD treatment and 12 patients continued with previous DMARD therapy. Clinical evaluation, blood tests, functional capacity evaluation and h-MRI were performed at the start of the investigation and at week 6. Tenosynovitis was evaluated on T1-weighted sequences with fat suppression after gadolinium as the presence of a peritendinous signal enhancement on axial images using a new method including wrist and finger tendons. The reliability, sensitivity to change and responsiveness of this method were also evaluated. RESULTS: Scores for tenosynovitis showed a significant reduction in the etanercept group compared with placebo (p=0.01) after 6 weeks of treatment. Adding MRI joint synovitis to tenosynovitis scores gave an even higher significant reduction in the etanercept group (p=0.007). A positive and statistically significant correlation between tenosynovitis and DAS28, erythrocyte sedimentation rate and C-reactive protein was found, but not with functional capacity. Responsiveness for tenosynovitis was small but was higher when joint synovitis scores were added. CONCLUSION: Addition of etanercept significantly reduced MRI tenosynovitis of the wrist and fingers in patients with active RA refractory to DMARD treatment. The method of scoring tenosynovitis showed good reliability and moderate responsiveness.
Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Articulaciones de los Dedos , Inmunoglobulina G/uso terapéutico , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Tenosinovitis/tratamiento farmacológico , Articulación de la Muñeca , Adulto , Anciano , Artritis Reumatoide/complicaciones , Quimioterapia Combinada , Etanercept , Femenino , Articulaciones de los Dedos/patología , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Tenosinovitis/etiología , Tenosinovitis/patología , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Articulación de la Muñeca/patologíaRESUMEN
OBJECTIVE: To demonstrate the efficacy of etanercept to reduce synovitis as measured by magnetic resonance imaging (MRI) as early as 6 weeks after starting treatment in patients with active rheumatoid arthritis (RA). METHODS: Twenty-two patients with active RA despite disease modifying antirheumatic drug (DMARD) treatment were included in this prospective, controlled study. Patients were randomized in 2 groups. In the treatment group, etanercept was added at usual doses during 6 weeks. In the control group, patients continued with prior DMARD therapy. MRI of the dominant wrist and 2nd-5th MCP joints were obtained at baseline and at 6 weeks and evaluated according to OMERACT recommendations. Results of changes in synovitis in the treatment group were compared with changes in the control group. RESULTS: Changes in synovitis measured by MRI of the hand (OMERACT evaluation) in the etanercept group showed a significant reduction after 6 weeks of treatment compared with no changes in the control group. Reduction of synovitis in the treatment group also showed good correlation with decrease of various clinical and laboratory measures. CONCLUSION: In patients with active RA despite DMARD therapy, etanercept, but not placebo, reduced synovitis as measured by MRI after 6 weeks.
Asunto(s)
Artritis Reumatoide/tratamiento farmacológico , Inmunoglobulina G/farmacología , Imagen por Resonancia Magnética , Membrana Sinovial/efectos de los fármacos , Sinovitis/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto , Anciano , Antirreumáticos/uso terapéutico , Artritis Reumatoide/patología , Huesos/efectos de los fármacos , Huesos/patología , Quimioterapia Combinada , Etanercept , Femenino , Humanos , Articulaciones/efectos de los fármacos , Articulaciones/patología , Masculino , Persona de Mediana Edad , Receptores del Factor de Necrosis Tumoral , Membrana Sinovial/patología , Sinovitis/patologíaRESUMEN
The ideal aim of treatment in rheumatoid arthritis (RA) is to suppress synovial inflammation and to stop or reduce structural joint damage progression. To evaluate joint damage in RA, radiographic assessment of hands and feet is the traditional method. Nevertheless, plain film radiography can only evaluate bone damage (erosion) and, indirectly, joint cartilage. Magnetic resonance imaging presents important advantages since allows to study, not only the cortical bone and the marrow, but also the synovial membrane, tendon and ligament structures,and adjacent soft tissue that usually are involved in early disease. Moreover, hand-magnetic resonance (h-MRI) has shown to be more sensitive than plain radiography in detecting early erosions and predicting progression of bone damage, allowing a rapid diagnosis and to start the most efficient therapy as well as to achieve better outcomes for this disease.