A serum metabolic biomarker panel for early rheumatoid arthritis.

Objective: There is an urgent need for novel biomarkers to improve the early diagnosis of rheumatoid arthritis (ERA). Current serum biomarkers used in the management of ERA, including rheumatoid factor and anti-cyclic citrullinated peptide (ACPA), show limited specificity and sensitivity. Here, we used metabolomics to uncover new serum biomarkers of ERA. Methods: We applied an untargeted metabolomics approach including gas chromatography time-of-flight mass spectrometry in serum samples from an ERA cohort (n=32) and healthy controls (n=19). Metabolite set enrichment analysis was performed to explore potentially important biological pathways. Partial least squares discriminant analysis and variable importance in projection analysis were performed to construct an ERA biomarker panel. Results: Significant differences in the content of 11/81 serum metabolites were identified in patients with ERA. Receiver operating characteristic (ROC) analysis showed that a panel of only three metabolites (glyceric acid, lactic acid, and 3-hydroxisovaleric acid) could correctly classify 96.7% of patients with ERA, with an area under the ROC curve of 0.963 and with 94.4% specificity and 93.5% sensitivity, outperforming ACPA-based diagnosis by 2.9% and, thus, improving the preclinical detection of ERA. Aminoacyl-tRNA biosynthesis and serine, glycine, and phenylalanine metabolism were the most significant dysregulated pathways in patients with ERA. Conclusion: A metabolomics serum-based biomarker panel composed of glyceric acid, lactic acid, and 3-hydroxisovaleric acid offers potential for the early clinical diagnosis of RA.

Relación entre la estación del año y la gravedad de los síntomas en pacientes con fibromialgia / Relationship between season of the year and severity of symptoms in patients with fibromyalgia

Antecedentes y objetivo: Es frecuente que los pacientes con fibromialgia refieran que ciertas estaciones del año agravan sus síntomas. Como objetivo primario se determinó la asociación entre síntomas claves de la fibromialgia y estación del año. Como objetivo secundario se determinó la existencia de diferencias en función de los niveles de ansiedad o depresión.Material y métodoMuestra de conveniencia formada por 471 participantes con fibromialgia evaluados antes de iniciar un tratamiento multidisciplinar. Se recogieron datos demográficos y meteorológicos y se evaluaron, mediante instrumentos estandarizados, la intensidad del dolor, la funcionalidad, la fatiga, la rigidez, la calidad del sueño, así como la ansiedad y la depresión.ResultadosLos diferentes grupos estacionales fueron homogéneos en edad, género, nivel educativo, estado marital y situación laboral. No se encontraron diferencias significativas en intensidad del dolor (F=1,334; p=0,265), funcionalidad (F=0,402; p=0,669), fatiga (F=0,714; p=0,490), rigidez (F=0,299; p=0,741), ansiedad (F=0,376; p=0,687), depresión (F=0,608; p=0,545), distrés psicológico (F=0,261; p=0,770), duración del sueño (F=1,507; p=0,223) o el índice de problemas de sueño (F=0,343; p=0,710).ConclusionesNo se han encontrado diferencias en la intensidad de los síntomas de la fibromialgia ni en los porcentajes de gravedad entre las distintas estaciones del año. La ansiedad ha sido más prevalente que la depresión, posiblemente debido a las propias características de la muestra, con mayoría de pacientes con perfil disfuncional. (AU)

Background and objective: Fibromyalgia patients often report that certain seasons aggravate their symptoms. The main objective was to determinate the association between key symptoms of fibromyalgia and the season of the year. A secondary objective was to determinate the existence of differences based on levels of anxiety or depression.Material and methodConvenience sample made up of 471 participants with fibromyalgia evaluated before starting multidisciplinary treatment. Demographic and meteorological data were collected. Clinical data were assessed with standardized instruments of pain intensity, functionality, fatigue, stiffness, sleep quality, anxiety and depression.ResultsThe different groups of participants were homogeneous for age, gender, educational level, marital status and employment situation. No significant differences were found in pain intensity (F=1.334; P=.265), functionality (F=.402; P=.669), fatigue (F=.714; P=.490), stiffness (F=.299; P=.741), anxiety (F=.376; P=.687), depression (F=.608; P=.545), psychological distress (F=.261; P=.770), sleep quantity (F=1.507; P=.223) or sleep disturbances (F=.343; P=.710).ConclusionsNo differences were found in the intensity of fibromyalgia symptoms, nor in the percentages of severity among the different seasons of the year. Anxiety was more prevalent than depression, possibly due to the characteristics of the sample itself, with the majority of patients with a dysfunctional profile. (AU)

[Relationship between season of the year and severity of symptoms in patients with fibromyalgia]. / Relación entre la estación del año y la gravedad de los síntomas en pacientes con fibromialgia.

BACKGROUND AND OBJECTIVE: Fibromyalgia patients often report that certain seasons aggravate their symptoms. The main objective was to determinate the association between key symptoms of fibromyalgia and the season of the year. A secondary objective was to determinate the existence of differences based on levels of anxiety or depression. MATERIAL AND METHOD: Convenience sample made up of 471 participants with fibromyalgia evaluated before starting multidisciplinary treatment. Demographic and meteorological data were collected. Clinical data were assessed with standardized instruments of pain intensity, functionality, fatigue, stiffness, sleep quality, anxiety and depression. RESULTS: The different groups of participants were homogeneous for age, gender, educational level, marital status and employment situation. No significant differences were found in pain intensity (F=1.334; P=.265), functionality (F=.402; P=.669), fatigue (F=.714; P=.490), stiffness (F=.299; P=.741), anxiety (F=.376; P=.687), depression (F=.608; P=.545), psychological distress (F=.261; P=.770), sleep quantity (F=1.507; P=.223) or sleep disturbances (F=.343; P=.710). CONCLUSIONS: No differences were found in the intensity of fibromyalgia symptoms, nor in the percentages of severity among the different seasons of the year. Anxiety was more prevalent than depression, possibly due to the characteristics of the sample itself, with the majority of patients with a dysfunctional profile.

Trajectories in early rheumatoid arthritis related fatigue over 10 years: results from the ESPOIR cohort.

OBJECTIVES: In a cohort of early rheumatoid arthritis (RA) patients, we aimed to determine and characterise fatigue trajectories over 10 years of follow-up and identify predictors of trajectory membership. METHODS: We selected patients fulfilling the 2010 ACR/EULAR criteria for RA included in the ESPOIR cohort. We used a cluster analysis to obtain fatigue (assessed by fatigue visual analogue scale) trajectories over the course of 10 years from enrolment. Chi-square tests or ANOVA were performed to evaluate differences of baseline variables between fatigue trajectories. Using a multinomial logistic regression we were able to identify predictors of trajectory membership. RESULTS: We analysed 598 patients with mean disease duration at enrolment of 26.2±40.9 days. Cluster analysis revealed 3 trajectories: high (18%), moderate (52%) and low fatigue (30%). Compared to patients with moderate or low fatigue trajectory, patients with high fatigue trajectory were predominantly women and reported significantly higher duration and intensity of morning stiffness, HAQ score, tender joints count, levels of pain, number of awakenings due to arthritis, frequency of fibromyalgic RA, levels of physician and patient global assessment, more frequent sleep problems, and increased psychological distress. Female patients with pain, psychological distress and presence of sicca symptoms had a higher risk of being in the high trajectory group. CONCLUSIONS: These findings suggest that levels of fatigue are rather stable over time in each trajectory. Baseline clinical measures and baseline patient-reported measures of functional status better distinguished the three fatigue trajectories. We did not find any differences between trajectories in baseline laboratory measures. Inflammatory activity was not a predictor of being in the high trajectory fatigue group.

A Serum Biomarker Panel of exomiR-451a, exomiR-25-3p and Soluble TWEAK for Early Diagnosis of Rheumatoid Arthritis.

Background: The etiology of rheumatoid arthritis (RA) remains poorly understood. Early and accurate diagnosis still difficult to achieve. Inflammatory related molecules released into the circulation such cytokines and exosome-derived microRNAs (exomiRNAs) could be good candidates for early diagnosis of autoimmune diseases. We sought to discover a serum biomarker panel for the early detection of RA based on exomiRNAs and inflammatory markers. Methods: A 179 miRNAs-microarray panel was analyzed in a pilot study (4 early RA and 4 controls). Validation of deregulated exomiRNAs was performed in a larger cohort (24 patients with early RA and 24 controls). miRNet software was used to predict exomiRNA gene-targets interactions. Potentially altered pathways were analyzed by Reactome pathway database search. STRING database was used to predict protein-protein interaction networks. Enzyme-linked immunosorbent assay was used to measure serum levels of sTWEAK and sCD163. Signature biomarker candidates were statistical analyzed. Results: We detected 11 differentially expressed exomiRNAs in early RA pilot study. Validation analysis revealed that 6/11 exomiRNAs showed strong agreement with the pilot microarray data (exomiR-144-3p, -25-3p, -15a-5p, -451a, -107 and -185-5p). sTWEAK and sCD163 biomarkers were significantly elevated in the serum of patients with early RA. Receiver operating characteristic (ROC) analysis showed that the best panel to diagnose early RA contained exomiR-451a, exomiR-25-3p and sTWEAK, and could correctly classify 95.6% of patients, with an area under the ROC curve of 0.983 and with 100% specificity and 85.7% sensitivity. The YWHAB gene was identified as a common target of the putative miRNA-regulated pathways. Conclusion: A novel serum biomarker panel composed of exomiR-451a, exomiR-25-3p and serum levels of sTWEAK may have use in the early clinical diagnosis of RA. A new predicted exomiRNA-target gene YHWAB has been identified and may have a relevant role in the development of RA.

Abatacept in interstitial lung disease associated with rheumatoid arthritis: national multicenter study of 263 patients.

OBJECTIVE: To assess the efficacy of abatacept (ABA) in RA patients with interstitial lung disease (ILD) (RA-ILD). METHODS: This was an observational, multicentre study of RA-ILD patients treated with at least one dose of ABA. ILD was diagnosed by high-resolution CT (HRCT). We analysed the following variables at baseline (ABA initiation), 12 months and at the end of the follow-up: Modified Medical Research Council (MMRC) scale (1-point change), forced vital capacity (FVC) or diffusion lung capacity for carbon monoxide (DLCO) (improvement or worsening ≥10%), HRCT, DAS on 28 joints evaluated using the ESR (DAS28ESR) and CS-sparing effect. RESULTS: We studied 263 RA-ILD patients [150 women/113 men; mean (s.d.) age 64.6 (10) years]. At baseline, they had a median duration of ILD of 1 (interquartile range 0.25-3.44) years, moderate or severe degree of dyspnoea (MMRC grade 2, 3 or 4) (40.3%), FVC (% of the predicted) mean (s.d.) 85.9 (21.8)%, DLCO (% of the predicted) 65.7 (18.3) and DAS28ESR 4.5 (1.5). The ILD patterns were: usual interstitial pneumonia (UIP) (40.3%), non-specific interstitial pneumonia (NSIP) (31.9%) and others (27.8%). ABA was prescribed at standard dose, i.v. (25.5%) or s.c. (74.5%). After a median follow-up of 12 (6-36) months the following variables did not show worsening: dyspnoea (MMRC) (91.9%); FVC (87.7%); DLCO (90.6%); and chest HRCT (76.6%). A significant improvement of DAS28ESR from 4.5 (1.5) to 3.1 (1.3) at the end of follow-up (P < 0.001) and a CS-sparing effect from a median 7.5 (5-10) to 5 (2.5-7.5) mg/day at the end of follow-up (P < 0.001) was also observed. ABA was withdrawn in 62 (23.6%) patients due to adverse events (n = 30), articular inefficacy (n = 27), ILD worsening (n = 3) and other causes (n = 2). CONCLUSION: ABA may be an effective and safe treatment for patients with RA-ILD.

Abatacept in patients with rheumatoid arthritis and interstitial lung disease: A national multicenter study of 63 patients.

OBJECTIVE: Interstitial lung disease (ILD) is one of the most serious complications of rheumatoid arthritis (RA). In the present study, we aimed to assess the efficacy of abatacept (ABA) in patients with ILD associated to RA. METHODS: National multicenter, non-controlled, open-label registry study of RA patients with ILD treated with ABA. RESULTS: 63 patients (36 women) with RA-associated ILD undergoing ABA therapy were studied. The mean ± standard deviation age at the time of the study was 63.2 ± 9.8 years. The median duration of RA and ILD from diagnosis were 6.8 and 1 year, respectively. RA was seropositive in 55 patients (87.3%). In 15 (23.8%) of 63 patients the development of ILD was closely related to the administration of synthetic or biologic disease modifying anti-rheumatic drugs. After a follow-up of 9.4 ± 3.2 months, two-thirds of patients remained stable whereas one-quarter experienced improvement in the Modified Medical Research Council scale. At that time forced vital capacity remained stable in almost two-thirds of patents and improved in one out of five patients assessed. Also, diffusing capacity of the lung for carbon monoxide remained stable in almost two-thirds and showed improvement in a quarter of the patients assessed. At 12 months, 50% of the 22 patients in whom chest HRCT scan was performed due persistence of respiratory symptoms showed stabilization, 8 (36.4%) improvement and 3 worsening of the HRCT scan pattern. Eleven of 63 patients had to discontinue ABA, mainly due to adverse events. CONCLUSION: ABA appears to be an effective in RA-associated ILD.

Lesión osteolítica cervical como presentación del síndrome SAPHO / SAPHO syndrome presenting as an osteolytic lesion of the neck

Se expone un caso de osteítis vertebral múltiple de presentación aguda con marcada afectación del estado general. Los hallazgos radiológicos, gammagráficos y de resonancia magnética obligaron al diagnóstico diferencial de un proceso neoplásico infiltrativo y de un origen infeccioso vertebral frente a la etiología inflamatoria. Por la presencia de osteítis múltiple no infecciosa, artritis esternoclavicular y la ulterior aparición de pustulosis plantar, se orientó como síndrome SAPHO. El tratamiento con infliximab consiguió la mejoría clínica, analítica y de las alteraciones radiológicas (AU)

We report a case of acute-onset multifocal vertebral osteitis with a marked impact on the patient's general health. The radiological, scintigraphic and magnetic resonance findings made it necessary to carry out a differential diagnosis to distinguish it from an infiltrative neoplastic process and determine whether it had an infectious or an inflammatory etiology. The presence of noninfectious multifocal osteitis and sternoclavicular arthritis and the subsequent development of plantar pustulosis pointed to SAPHO syndrome. Treatment with infliximab led to improvement in the clinical symptoms, laboratory values and radiological abnormalities (AU)

SAPHO syndrome presenting as an osteolytic lesion of the neck. / Lesión osteolítica cervical como presentación del síndrome SAPHO.

We report a case of acute-onset multifocal vertebral osteitis with a marked impact on the patient's general health. The radiological, scintigraphic and magnetic resonance findings made it necessary to carry out a differential diagnosis to distinguish it from an infiltrative neoplastic process and determine whether it had an infectious or an inflammatory etiology. The presence of noninfectious multifocal osteitis and sternoclavicular arthritis and the subsequent development of plantar pustulosis pointed to SAPHO syndrome. Treatment with infliximab led to improvement in the clinical symptoms, laboratory values and radiological abnormalities.

Nefropatía IgA en las enfermedades reumáticas / Immunoglobulin A nephropathy in rheumatic diseases

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Enfermedad de Behçet y enteropatía perdedora de proteínas secundaria a linfangiectasia intestinal / Behc ̧ et disease and protein-losing enteropathy due to intestinal lymphangiectasia

Se describe el caso de un paciente con enfermedad de Behçet y enteropatía perdedora de proteínas secundaria a linfangiectasia intestinal (AU)

We report an unusual case of a patient with Behçet's disease that developed protein-losing enteropathy due to intestinal lymphangiectasia (AU)

Eficacia de bosentán en el tratamiento de las úlceras digitales de la tromboangitis obliterante / Efficacy of bosentan in the treatment of digital ulcers secondary to thromboangiitis obliterans

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Polimialgia reumática con derrame pleuropericárdico: una asociación infrecuente / Rheumatic polymyalgia with pleuropericardial effusion: an uncommon association

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Behçet disease and protein-losing enteropathy due to intestinal lymphangiectasia.

We report an unusual case of a patient with Behçet's disease that developed protein-losing enteropathy due to intestinal lymphangiectasia.

¿Cuál es la evolución de las artritis indiferenciadas? / What is the outcome of undifferentiated arthritis?

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