Frecuencia de eventos cardiovasculares en pacientes con lupus eritematoso sistémico / Frequency of cardiovascular events in patients with systemic lupus erythematosus

Resumen Introducción: el progreso en los tratamientos para el lupus eritematoso sistémico (LES) resultó en una disminución de la mortalidad; sin embargo, la enfermedad cardiovascular y las complicaciones infecciosas aún son las principales causas de muerte. La evidencia apoya la participación del sistema inmunológico en la generación de la placa aterosclerótica, así como su conexión con las enfermedades autoinmunes. Objetivos: describir la frecuencia de eventos cardiovasculares (ECV) en el Registro de Lupus Eritematoso Sistémico de la Sociedad Argentina de Reumatología (RELESSAR) transversal, así como sus principales factores de riesgo asociados. Materiales y métodos: estudio descriptivo y transversal para el cual se tomaron los pacientes ingresados en el registro RELESSAR transversal. Se describieron las variables sociodemográficas y clínicas, las comorbilidades, score de actividad y daño. ECV se definió como la presencia de al menos una de las siguientes patologías: enfermedad arterial periférica, cardiopatía isquémica o accidente cerebrovascular. El evento clasificado para el análisis fue aquel posterior al diagnóstico del LES. Se conformaron dos grupos macheados por edad y sexo 1:2. Resultados: 1515 pacientes mayores de 18 años participaron del registro. Se describieron 80 pacientes con ECV (5,3%). En este análisis se incluyeron 240 pacientes conformando dos grupos. La edad media fue de 47,8 (14,4) y 47,6 (14,2) en el grupo con y sin ECV respectivamente. Los pacientes con ECV tuvieron mayor duración del LES en meses, mayor índice de Charlson, mayor SLICC (Systemic Lupus International Collaborating Clinics/American College of Rheumatology), mayor frecuencia de manifestaciones neurológicas, síndrome antifosfolípido, hospitalizaciones y uso de ciclofosfamida. Las únicas variables asociadas en el análisis multivariado fueron el índice de Charlson (p=0,004) y el SLICC (p<0,001). Conclusiones: los ECV influyen significativamente en nuestros pacientes, y se asocian a mayor posibilidad de daño irreversible y comorbilidades.

Abstract Introduction: progress in treatments for systemic lupus erythematosus (SLE) has resulted in a decrease in mortality; however, cardiovascular and infectious diseases remain the leading causes of death. Evidence supports the involvement of the immune system in the generation of atherosclerotic plaque, as well as its connection to autoimmune diseases. Objectives: to describe the frequency of cardiovascular disease (CVD) in the cross-sectional RELESSAR registry, as well as its associated variables. Materials and methods: a descriptive and cross-sectional study was performed using patients admitted to the cross-sectional RELESSAR registry. Sociodemographic variables, clinical variables, comorbidities, activity and damage scores were described. CVD was defined as at least one of the following: peripheral arterial disease, ischemic heart disease, or cerebrovascular accident. All patients with at least one CVD were included in our analysis (heart attack, central nervous system vascular disease, and peripheral arteries atherosclerotic disease). The event classified for the analysis was that after the diagnosis of SLE. SLE diagnosis was previous to CVD. Two groups matched by age and sex, 1:2 were formed. Results: a total of 1515 patients older than 18 years participated in the registry. Eighty patients with CVD (5.3%) were described in the registry. Two-hundred and forty patients were included, according to two groups. The mean age was 47.8 (SD 14.4) and 47.6 (SD 14.2) in patients with and without CVD, respectively. Patients with CVD had a longer duration of SLE in months, a higher Charlson index, a higher SLICC, increased frequency of neurological manifestations, antiphospholipid syndrome, hospitalizations, and use of cyclophosphamide. The associated variables in the multivariate were the Charlson Index (p=0.004) and the SLICC (p<0.001). Conclusions: CVDs have a significant influence on our patients, being associated with a greater possibility of damage and comorbidities.

Assessment of Intracellular Amyloid Formation in Fixed and Live Bacteria Using Fluorescence Microscopy.

Although amyloid aggregation has been generally associated with protein misfolding and neurodegenerative diseases in mammals, bacteria and other organisms have harnessed amyloidogenesis to perform diverse biological processes. These functional amyloids, some of them secreted and others intracellular, require that the producing cells keep aggregation under control in the cytoplasm upon protein translation, preventing their inherent toxicity. Thus, it is highly relevant to understand how intracellular amyloid formation occurs and is regulated, its metabolic consequences, and the formation dynamics and fate of the amyloid inclusions upon cell division. This chapter describes methods leveraging fluorescence microscopy and fixed- or live-cell imaging to monitor intracellular amyloid formation in bacterial cells.

Identification of Aggregation-Prone and Gatekeeper Residues in Bacterial Amyloids Using Site-Directed Mutagenesis and Flow Cytometry.

Bacterial functional amyloids are remarkable examples of how amyloid aggregation can be kept under control and even leveraged to perform diverse biological processes. In this context, it is highly relevant to understand how amyloidogenesis is modulated by relevant factors, including key amino acids promoting or preventing aggregation. This chapter describes a methodology to identify critical residues for amyloid formation in bacterial proteins, based on mutant construction guided by bioinformatics prediction, their expression in bacteria, and their analysis by flow cytometry. Additionally, we describe a simple downstream analysis of selected mutants to assess their in vitro aggregation properties upon protein purification. We applied the proposed methodology to identify critical residues modulating the aggregation of the antimicrobial peptide microcin E492, a well-studied model of bacterial amyloids.

Multicenter lupus register from Argentina, the RELESSAR database: Influence of ethnicity on disease phenotype.

OBJECTIVE: The objective is to describe the main characteristics of patients with systemic lupus erythematosus (SLE) in Argentina and to examine the influence of ethnicity on the expression of the disease. PATIENTS AND METHODS: RELESSAR is a multicentre register carried out by 106 researchers from 67 rheumatologic Argentine centres. It is a cross-sectional study of SLE (1982/1997 ACR) patients. RELESSAR electronic database includes demographic, cumulative SLE manifestations, SELENA-SLEDAI, SLICC-SDI, Katz's severity and Charlson's comorbidity indexes and treatment patterns. RESULTS: We included 1,610 patients, 91.7% were female with a median age at diagnosis of 28.1 ± 12.8; 96.2% met ≥4 ACR 1982/97 criteria. Frequent manifestations were arthritis (83.5%), malar rash (79.5%), photosensitivity (75.3%), haematological (63.8%) and renal disease (47.4%), antinuclear antibodies (96%), anti-dsDNA (66.5%) and anti-Smith antibodies (29%). The mean Selena-SLEDAI score at last visit was 3.18 (SD 4.3) and mean SDI was 1 (SD 1.3). The accumulated treatments most frequently used were antimalarials (90.4%), corticosteroids (90%), azathioprine (31.8%), intravenous cyclophosphamide (30.2%), mycophenolate mofetil or mycophenolic acid (24.5%), methotrexate (19.3%), belimumab 5.3% and rituximab 5.1%. Refractory lupus was diagnosed in 9.3% of the cases. The main causes of death were lupus activity (25.0%), activity and concomitant infections (25.0%), infections (18.2%), vascular disease (13.6%) and cancer (4.5%). Mortality was associated with higher SLEDAI, Katz, damage indexes and comorbidities. Of the 1610 patients included, 44.6% were Caucasian, 44.5% Mestizo, 8.1% Amerindian and 1.2% Afro-Latin American. Mestizo patients had higher male representation, low socioeconomic status, more inadequate medical coverage, fewer formal years of education and shorter disease duration. Polyadenopathies and Raynaud's phenomenon were more frequent in Caucasians. In the logistic regression analysis higher damage index (OR 1.28, CI 95% 1.02-1.61, p = 0.03) remained associated to mestizo ethnicity. CONCLUSIONS: This study represents the largest number of adult patients with SLE studied in Argentina. Caucasian patients were differentiated by having Raynaud's phenomenon and polyadenopathy more frequently, while patients of Mestizo origin had higher damage indexes.

Lupus en Argentina. Pacientes no respondedores al tratamiento estándar y belimumab como posible opción. Datos del registro RELESSAR / Lupus in Argentina. Non-responders to standard treatment and belimumab as a possible option. RELESSAR record data

Introducción: el lupus es una enfermedad compleja y varias veces de difícil abordaje. Alcanzar la remisión es uno de los objetivos, incorporando opciones terapéuticas. Objetivos: describir las características generales de los pacientes según el estado de la enfermedad y el uso de belimumab. Materiales y métodos: estudio de corte transversal, registro RELESSAR. Se definió el estado de la enfermedad como: remisión: SLEDAI=0 y sin corticoides; baja actividad de la enfermedad: SLEDAI >0 y ≤4 y sin corticoides; control no óptimo: SLEDAI >4 y cualquier dosis de corticoides. Resultados: se incluyeron 1.277 pacientes, 23,4% en remisión, 12,6% en baja actividad y 63,8% con control no óptimo. En este último grupo eran más jóvenes y con menor duración de la enfermedad; presentaban mayores índices de actividad y cronicidad, y mayor empleo de inmunosupresores. Solo el 22,3% de los pacientes con criterio potencial de uso de belimumab (lupus eritematoso sistémico activo a pesar del tratamiento estándar) lo recibía en ese momento. Las variables asociadas a hospitalizaciones fueron: terapia con corticoides, ciclofosfamida y mayor SLICC. Conclusiones: se refleja la complejidad del manejo de estos pacientes y se visualizan aspectos estructurales como la desigualdad. El uso del belimumab resultaría beneficioso en los pacientes seleccionados.

Introduction: lupus is a complex disease and often difficult to approach. Achieving remission is one of the objectives, incorporating therapeutic options. Objectives: to describe the characteristics of the patients and the use of belimumab, according to the status of the disease. Materials and methods: cross-sectional study. Patients of the RELESSAR registry. Stratification: Remission: SLEDAI=0 and without corticosteroids. Low disease activity SLEDAI> 0 and ≤4 and without corticosteroids and non-optimal control: SLEDAI> 4 and any dose of corticosteroids. Results: a total of 1,277 patients were included, 23.4% in remission, 12.6% in low disease activity and 63.8% in non-optimal control. The last group was younger and had a shorter duration of the disease. They had higher activity and chronicity indices and greater use of immunosuppressants. Only 22.3% of the patients with potential criteria for the use of belimumab (activity disease despite standard treatment) were receiving it. The variables associated with hospitalizations were: corticosteroids, cyclophosphamide and higher SLICC. Those associated with severe infection: mycophenolate mofetil, azathioprine, corticosteroids, and higher SLICC. Conclusions: the complexity of the management of these patients is reflected, visualizing structural aspects such as inequality. The use of belimumab could be beneficial in selected patients.

Ultrasound-detected tenosynovitis as a risk factor for flares in rheumatoid arthritis patients in clinical remission.

BACKGROUND: Our objective was to investigate the value of ultrasound (US) detected synovitis and tenosynovitis as risk factors for short term flare in rheumatoid arthritis (RA) patients in clinical remission. METHODS: Consecutive RA patients in clinical remission (DAS28 ERS < 2.6) for at least 3 months underwent Power Doppler ultrasound (PDUS) examination of 1st to 6th extensor compartments at the wrist, 2nd to 5th finger flexor, posterior tibial tendon, and peroneal tendons. To assess synovitis, carpal joints, 1st to 5th metacarpophalangeal (MCP) joints, and 2nd to 5th interphalangeal proximal (IPP) joints were bilaterally examined. Synovitis and tenosynovitis were defined according to OMERACT. Patients were followed for 1 year. Disease flare was defined as an increase in disease activity generating the need for a change in therapy by the attending rheumatologist. RESULTS: Ninety patients were included. After 1 year of follow-up, 26 patients (29%) experienced a flare. At baseline 39%, 23% and 8% had US-detected synovitis, tenosynovitis or both, respectively. In the 1-year period after the baseline US examination, US-detected tenosynovitis (RR: 4.9; 95% CI: 2.2-10.8) was associated with an increased risk of exacerbation. This association was not shown with US-detected synovitis (RR: 1.3; 95% CI: 0.76-2.2). In the multivariate analysis, only subclinical tenosynovitis (OR: 9.8; 95% CI: 2.5-39.1; p = 0.001) and baseline DAS28 (OR: 5.7; 95% CI: 1.1-31.6; p = 0.047) were significantly associated with an increased risk of having a flare. CONCLUSION: In our study, subclinical tenosynovitis was associated with disease flare in patients with RA in clinical remission. KEY POINTS: • Synovitis and tenosynovitis are risk factors for short term flare in RA patients in clinical remission. • Subclinical tenosynovitis, but not synovitis, was associated with disease flare in patients with unstable remission. • Ultrasound-detected tenosynovitis could be useful to predict relapses in RA patients in clinical remission.

Validation and adaptation of the Spanish version of the systemic lupus activity questionnaire (S-SLAQ) in an Argentinean population.

OBJECTIVES: To validate the systemic lupus activity questionnaire (SLAQ) in Spanish language. METHODS: The SLAQ questionnaire was translated and adapted in Spanish. Consecutive SLE patients from 8 centers in Argentina were included. A rheumatologist completed a Systemic Lupus Activity Measure (SLAM), Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K, and a physician's assessment. Reliability was assessed by internal consistency (Cronbach's alpha), stability by test-retest reliability (intraclass correlation coefficient), and construct validity by evaluating the correlation with clinically relevant scores. Sensitivity and specificity for clinically significant disease activity (SLEDAI ≥6) of different S-SLAQ cut-off points were evaluated. RESULTS: We included 97 patients ((93% female, mean age: 40 years (SD14.7)). Internal consistency was excellent (Cronbach's alpha = 0.84, p < 0.001), and the intraclass correlation coefficient was 0.95 (p < 0.001). Mean score of S-SLAQ was 8.2 (SD 7.31). Correlation of S-SLAQ was moderate with Patient NRS (r= 0.63 p< 0.001), weak with SLAM-no lab (r = 0.42, p <0.001) and SLAM (r = 0.38, p < 0.0001), and very weak with SLEDAI-2K (r = 0.15, p =0.1394). Using the S-SLAQ cutoff of five points, the sensitivity was 72.2% and specificity was 37.9%, for clinically significant disease activity. CONCLUSIONS: The S-SLAQ showed good validity and reliability. A good correlation, similar to the original instrument, was observed with patient´s global disease activity. No correlation was found between S-SLAQ and gold standard disease activity measures like SLEDAI-2K and SLAM. The S-SLAQ cutoff point of 5 showed a good sensitivity to identify the active SLE population and therefore could be an appropriate screening instrument for disease activity in clinical and epidemiological studies.

Participación laboral en espondiloartritis axial radiográfica y no radiográfica / Labor participation in radiographic and non-radiographic axial spondyloarthritis

Introducción: las limitaciones laborales son un punto importante a considerar en el tratamiento de la espondiloartritis axial (EspAax) dado que esta enfermedad afecta a las personas en la etapa más productiva de la vida. Objetivos: describir la situación laboral en pacientes con EspAax de Argentina, incluyendo la espondilitis anquilosante (EA) y la espondiloartritis axial no radiográfica (EspAax-nr), y evaluar los factores asociados a la pérdida de productividad laboral (PPL) en esta cohorte nacional y los factores asociados a estar empleado. Materiales y métodos: en este estudio transversal y multicéntrico se incluyeron pacientes con diagnóstico de EA y EspAax-nr según los criterios de clasificación de la Assessment of SpondyloArthritis international Society (ASAS 2009) y en edad laboral (≤65 años). Los objetivos principales fueron evaluar la situación laboral, el ausentismo y el presentismo, valorados por el cuestionario Work Productivity and Activity Impairment Spondyloarthritis (WPAI-SpA). Se utilizó el coeficiente de Spearman para evaluar la correlación entre las medidas de la enfermedad y la PPL. Se realizó un análisis bivariado y multivariado para evaluar los factores asociados a estar empleado. Resultados: se incluyeron 129 pacientes con EspAax, 95 (73,6 %) con EA y 34 (26,4%) con EspAax-nr. La mediana (p25-75) de edad fue de 45 (35-55) años. La duración mediana de la enfermedad fue de 62 (24-123) meses y el retraso en el diagnóstico fue de 24 (6-72) meses. Sesenta (46,5%) pacientes estaban empleados. La mediana (p25-75) de presentismo de los pacientes con EA fue del 29,6% (0-57) y del 30% (20-40) para los pacientes con EspAax-nr (p=0,02). Asimismo, la mediana (p25-75) de PPL fue del 30% en ambos grupos de pacientes. Se encontró una correlación positiva entre la PPL y las siguientes variables: ASDAS (Rho:0.60), BASDAI (Rho:0.50), BASFI (Rho:0.60), ASQoL (Rho:0.60) y ASAS health index (Rho:0.54). En el análisis bivariado, los factores asociados al desempleo fueron el diagnóstico de EA, la edad avanzada, la mayor duración de la enfermedad, las comorbilidades (hipertensión y diabetes), el menor número de años de educación, la peor calidad de vida y la menor capacidad funcional. En el análisis multivariado, una mejor función física (evaluada por BASFI) se asoció de forma independiente a estar empleado. Conclusiones: este estudio demostró que la PPL en esta cohorte nacional fue del 30% en la EspAax. Se asoció con la actividad de la enfermedad, el estado de salud, la calidad de vida y la capacidad funcional. Una mejor función física se relacionó en forma independiente con una mayor probabilidad de mantener a los pacientes con EspAax empleados.

Introduction: work disability is an important outcome in the treatment of spondyloarthritis (SpA) since this disease affects people in the most productive stage of life. Objectives: to investigate working status in patients with axial spondyloarthritis (axSpA) from Argentina, including ankylosing spondylitis (AS) and nonradiographic axial SpA (nr-axSpA), and to evaluate factors associated with work productivity loss (WPL) in this national cohort and factors associated with being employed. Materials and methods: patients with a diagnosis of AS and nr-axSpA according to Assessment of SpondyloArthritis international Society (ASAS 2009) classification criteria and in working age (≤65 years) were included in this multicentric cross-sectional study. Outcomes of interest were employment status, absenteeism and presenteeism, assessed by the Work Productivity and Activity Impairment Spondyloarthritis (WPAI-SpA) questionnaire. Spearman's coefficient was used to assess the correlation between disease measures and WPL. Bivariate and multivariate analysis were performed in order to evaluate factors associated with being employed. Results: 129 patients with axSpA were included, 95 (73.6%) with AS and 34 (26.4%) with nr-axSpA. Median (p25-75) age of 45 (35-55) years. Median (p25-75) disease duration was 62 (24-123) months and diagnosis delay was 24 (6-72) months. 60 (46.5%) of the patients were employed. Median (p25-75) presenteeism of AS patients was 29.6% (0-57) and 30% (20-40) for patients with EspAax-nr (p=0.02). Median (p25-75) WPL was 30% in both groups of patients. A positive correlation was found between WPL and the following variables: ASDAS (Rho:0.60), BASDAI (Rho:0.50), BASFI (Rho:0.60), ASQoL (Rho:0.60) and ASAS health index (Rho:0.54). In the bivariate analysis, the factors associated with unemployment were AS diagnosis, older age, longer disease duration, comorbidities (hypertension and diabetes), fewer years of education, worse quality of life and lower functional capacity. In the multivariate analysis, better physical function (assessed by BASFI) was independently associated with being employed. Conclusions: this study showed that WPL in this national cohort was 30% in axSpA. It was associated with disease activity, health status, quality of life and functional capacity. Better physical function was independently associated with a higher likelihood of keeping patients with axSpA employed.

Recognition of spondyloarthritis lesions on magnetic resonance imaging: Results of an educational intervention.

BACKGROUND: Magnetic resonance imaging (MRI) is a fundamental diagnostic tool in axial spondyloarthritis (SpA), allowing us an earlier diagnosis of the disease compared to radiography. OBJECTIVE: To compare the performance of a recognition test on SpA MRI lesions and theoretical knowledge, before and after carrying out an educational intervention (hands-on workshop). We also evaluated whether the successes in the tests were associated with the individual characteristics of the participants. METHODS: A test was carried out involving 10 questions (seven for image recognition and three for theoretical knowledge) before and after the attendance to an MRI workshop in SpA performed in different cities in Argentina. The number of correct answers was assessed before and after the workshop; good performance was defined as the achievement of 6 correct answers on average between the pre- and post-test. Participants' characteristics were collected. RESULTS: A total of 106 participants were evaluated. Average of correct answers before and after the workshop were 5.3 and 6.8, respectively (P = .0001); 65% of participants achieved good performance. Performance is not associated with the characteristics of trained physicians. CONCLUSION: MRI training workshops in SpA allow rheumatologists to improve recognition of acute inflammatory and structural lesions. The long-term effects of such training need further evaluation.

Performance of Ultrasonography Compared to Conventional Radiography for the Diagnosis of Osteoarthritis in Patients With Knee Pain.

Purpose: To investigate the performance of ultrasonography (US) for the detection of knee osteoarthritis (OA) in patients suffering from knee pain, compared to conventional radiographs. Methods: Cross-sectional study performed at a university teaching hospital. Consecutive patients complaining of unilateral or bilateral mechanical knee pain who signed an informed consent were included. All patients underwent simultaneously an ultrasonographic and a radiographic evaluation of the knee. Exclusion criteria were age under 18 years, prior diagnosis of knee OA, diagnosis of inflammatory arthritis, history of knee surgery or trauma, severe knee deformities, and corticosteroid injection within the last 2 months. The diagnostic properties of US for the detection of knee OA were evaluated using radiological data as the reference method. Evaluated test properties were sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the positive and negative likelihood ratio (LR+ and LR-). Results: Three-hundred twenty-two knees (281 patients) were included. Radiographic degenerative changes were present in 56.8% (183) of the evaluated knees. Regarding the diagnostic properties of the US, the presence of either osteophytes or the compromise of the femoral hyaline cartilage had the best sensitivity to detect OA (95%), with a NPV of 92% and a LR- of 0,07, while the combined identification of osteophytes and compromise of the femoral hyaline cartilage had the best specificity (94%), with 94% PPV and a LR+ of 13. Conclusion: US demonstrated an excellent sensitivity with an adequate specificity for the detection of radiographic knee OA.

¿Permiten los entrenamientos de resonancia magnética en espondiloartritis mejorar la performance de los reumatólogos para el reconocimiento de secuencias y lesiones? / Does MRI training in spondyloarthritis improve the performance of rheumatologists on the recognition of sequences and lesions?

Introducción: La resonancia magnética (RM) es una herramienta diagnóstica fundamental en la espondiloartritis (EspA) axial. Objetivo: Estimar el porcentaje de aciertos en el reconocimiento de lesiones en RM de EspA y conocimientos teóricos, antes y después de realizar una intervención educativa. Estimar si la buena performance en los test se asocia a características individuales de los médicos. Materiales y métodos: Estudio analítico, con intervención activa, se midieron los resultados antes y después de un test con 10 preguntas antes y después del desarrollo de un taller de imágenes de RM en EspA en ciudades distintas de Argentina. Se consideró buena performance a quienes lograron más de 12 puntos entre las dos evaluaciones. Resultados: Se evaluaron en total 106 médicos. Los resultados de los test (total 10 preguntas) antes y después del taller fueron 53% de respuestas correctas y 68% respectivamente (p: 0.000). El 65% de los médicos alcanzaron una buena performance (más de 12 respuestas correctas). Conclusión: El porcentaje de aciertos fue mayor después del taller en forma general, la buena performance no se asoció a ninguna característica especifica de los médicos evaluados.

Introduction: Magnetic resonance imaging (MRI) is a fundamental diagnostic tool in axial spondyloarthritis, it has allowed us, unlike radiography, to diagnose this pathology much earlier. Objective: To estimate the percentage of correct answers in the recognition of SpA MRI lesions and theoretical knowledge, before and after performing an educational intervention. Estimate if the good performance in the tests is associated with individual characteristics of the doctors. Methods: A test was carried out with 10 questions (7 for image recognition and 3 for theoretical knowledge) before and after the development of an MRI image workshop in EspA in diferents cities in Argentina. The correct response number was considered before and after the workshop, and those who achieved more than 12 points between the two evaluations were considered good performance. The following physician characteristics were collected. Results: A total of 106 physicians were evaluated. The results of the tests (total 10 questions) before and after the workshop were 53% and 68% correct, respectively (p:0.000). 65% of the physicians achieved a good performance (more than 12 correct).

¿Permiten los entrenamientos de resonancia magnética en espondiloartritis mejorar la performance de los reumatólogos para el reconocimiento de secuencias y lesiones? / Do magnetic resonance training in spondyloarthritis improve the performance of rheumatologists for the recognition of sequences and lesions?

Introducción: La resonancia magnética (RM) es una herramienta diagnóstica fundamental en la espondiloartritis (EspA) axial. Objetivo: Estimar el porcentaje de aciertos en el reconocimiento de lesiones en RM de EspA y conocimientos teóricos, antes y después de realizar una intervención educativa. Estimar si la buena performance en los test se asocia a características individuales de los médicos. Materiales y métodos: Estudio analítico, con intervención activa, se midieron los resultados antes y después de un test con 10 preguntas antes y después del desarrollo de un taller de imágenes de RM en EspA en ciudades distintas de Argentina. Se consideró buena performance a quienes lograron más e 12 puntos entre las dos evaluaciones. Resultados: Se evaluaron en total 106 médicos. Los resultados de los test (total 10 preguntas) antes y después del taller fueron 53% de respuesta correctas y 68% respectivamente (p: 0.000). El 65% de los médicos alcanzaron una buena performance (más de 12 respuesta correctas). Conclusión: El porcentaje de aciertos fue mayor después del taller en forma general, la buena performance no se asoció a ninguna característica especifica de los médicos evaluados.

Introduction: Magnetic resonance imaging (MRI) is a fundamental diagnostic tool in axial spondyloarthritis, it has allowed us, unlike radiography, to diagnose this pathology much earlier. Objective: To estimate the percentage of correct answers in the recognition of SpA MRI lesions and theoretical knowledge, before and after performing an educational intervention. Estimate if the good performance in the tests is associated with individual characteristics of the doctors. Methods: A test was carried out with 10 questions (7 for image recognition and 3 for theoretical knowledge) before and after the development of an MRI image workshop in EspA in diferents cities in Argentina. The correct response number was considered before and after the workshop, and those who achieved more than 12 points between the two evaluations were considered good performance. The following physician characteristics were collected. Results: A total of 106 physicians were evaluated. The results of the tests (total 10 questions) before and after the workshop were 53% and 68% correct, respectively (p:0.000). 65% of the physicians achieved a good performance (more than 12 correct)

Spanish Validation of the GEPARD Questionnaire for the Detection of Psoriatic Arthritis in Argentinian Patients with Psoriasis.

BACKGROUND/OBJECTIVE: Psoriatic arthritis (PsA) is preceded by psoriasis in approximately 80% of cases. Dermatologists are pivotal for early detection. It is important to have simple tools that allow the detection of PsA in patients with skin psoriasis. The aim of our study was to evaluate the performance of an adapted version of the GEPARD Questionnaire in Spanish in Argentinian patients with psoriasis. METHODS: This is a cross-sectional study. A new Spanish (Argentinian) (GEPARDa) translated version of the original questionnaire (German) was developed and then tested as a diagnostic tool in patients with psoriasis, PsA, osteoarthritis associated to psoriasis, and osteoarthritis, all evaluated by rheumatologists who used the CASPAR criteria. RESULTS: Eighty-three patients were included (55 [66.3%] women with a mean age of 50.7 years [SD 6.3]). Forty-four patients had PsA (29 [34.9%] patients had previous diagnosis of PsA, and 15 [18%] were newly diagnosed after referral by their dermatologists), and 39 patients were without PsA (18 [21.6%] patients had psoriasis without articular involvement, 6 [7.22%] had psoriasis associated with osteoarthritis, and 15 [18%] had osteoarthritis). An area under the curve of 0.9554 (SD 0.01; 95% CI 0.91-0.99) was calculated considering the CASPAR criteria as the gold standard. With a cutoff of ≥6 the questionnaire showed a sensitivity of 88.64%, a specificity of 89.74%, a positive likelihood ratio of 8.6, and a negative likelihood ratio of 0.12. CONCLUSIONS: The GEPARDa version has proven to be a diagnostic tool with excellent performance so that it can be considered a valid tool for the detection of PsA in Argentinian patients.

Value of Color Doppler Ultrasound Assessment of Sacroiliac Joints in Patients with Inflammatory Low Back Pain.

OBJECTIVE: To evaluate the diagnostic value of color Doppler ultrasound (CDUS) for the detection of sacroiliitis, in patients with inflammatory back pain (IBP). METHODS: Consecutive patients with IBP and suspected axial spondyloarthritis (SpA), but without a definitive diagnosis, were included. Consecutive patients with defined SpA and axial involvement were included as a control group. All patients underwent clinical evaluation, magnetic resonance imaging (MRI), and CDUS of sacroiliac joints (SIJ) within the same week. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the diagnosis of sacroiliitis by CDUS were calculated, using MRI as the gold standard. RESULTS: There were 198 SIJ evaluated in 99 patients (36 with previous SpA). There were 61 men (61.6%), with a mean age of 39.8 years (SD 11.3) and median disease duration of 24 months (IQR 12-84). At the patient level, CDUS had a sensitivity of 63% (95% CI 48.7-75.7%) and a specificity of 89% (95% CI 76-96%). The PPV was 87.2% (95% CI 72.6-95.7%) and the NPV was 66.7% (95% CI 53.3-78.3%). At joint level, CDUS had a sensitivity of 60% (95% CI 49-70%) and a specificity of 93% (95% CI 88-98%). The PPV was 83% (95% CI 78-95%) and the NPV was 43% (95% CI 33-56%). The sensitivity of CDUS for the diagnosis of axial SpA was 54% (95% CI 36.6-71.2%), specificity was 82% (95% CI 63.1-93.9%), PPV was 79% (95% CI 57.8-92.9%), and NPV was 59% (95% CI 42.1-74.4%). CONCLUSION: CDUS showed adequate diagnostic properties for detection of sacroiliitis and is a useful tool in patients with IBP.

Reliability of OMERACT ultrasound elementary lesions in gout: results from a multicenter exercise.

The aim of this study was to evaluate the reliability of the outcome measures in rheumatology (OMERACT) definitions for ultrasound (US) elementary lesions in gout through an image reading exercise. Images from patients with gout (static images and videos) were collected. As an initial step, we carried out a image reading exercise within the experts of the Pan-American League of Associations for Rheumatology (PANLAR) US Study Group (n = 16). The following step consisted in a web-based exercise with the participation of larger number of sonographers (n = 63) from different centers. Images were rated evaluating the presence/absence of any US elementary lesion. Inter- and intra-reader reliabilities were analyzed using kappa coefficients. Participants were stratified according to their level of experience. In the first exercise, inter-reader kappa values were 0.45 for aggregates, 0.57 for tophus, 0.69 for erosions, and 0.90 for double contour (DC). Intra-reader kappa values were 0.86, 0.76, 0.80, and 0.90, respectively. The web-based exercise showed inter-reader kappa values for aggregates, tophus, erosions, and DC of 0.42, 0.49, 0.69, and 0.79, respectively. The intra-reader kappa values were 0.62, 0.69, 0.77, and 0.85, respectively. Reliability was not influenced by the sonographer's level of experience. The reliability of the new OMERACT US definitions for elementary lesions in gout ranged from moderate to excellent, depending on the type of lesion.

Tenosinovitis subclínica detectada por ecografía en pacientes con artritis reumatoidea en remisión clínica sostenida / Subclinical tenosynovitis detected by ultrasound in patients with rheumatoid arthritis under sustained clinical remission

El objetivo fue evaluar la prevalencia de tenosinovitis detectada por ecografía-doppler en pacientes con Artritis Reumatoidea (AR) en remisión clínica sostenida, determinar su asociación con las características de la enfermedad y determinar si la presencia de tenosinovitis ecográfica podría agregar información a la sinovitis para definir remisión ecográfica. Se incluyeron 60 pacientes con AR en remisión clínica (DAS28 <2,6, CDAI <2,8 y/o SDAI <3,3) sostenida a quienes se les realizó una ecografía con señal doppler de poder (DP). Un reumatólogo entrenado evaluó en forma bilateral: 1°-6° compartimentos extensores a nivel del carpo, 2°-5° tendones flexores de los dedos de las manos, tibial posterior, peroneo lateral corto y largo. A nivel articular se evaluaron en forma bilateral: carpo, 2°-5° metacarpofalángicas y 2°-5° interfalángicas proximales. Se definió remisión ecográfica a la ausencia de sinovitis en escala de grises (EG) grado ≥2 y la ausencia de señal DP a nivel articular o tendinoso. Se detectó tenosinovitis por EG grado ≥2 y señal DP ≥1 en 14 (23%; IC 95%: 12-34) y 13 (21,7%; IC 95%: 10-32) pacientes, respectivamente. Los tendones más frecuentemente afectados fueron: 6° compartimento extensor del carpo, tibial posterior y 3° tendón flexor tibial posterior. En el análisis multivariado, la única variable que se asoció con la presencia de tenosinovitis por ecografía-doppler fue la ERS (OR: 1,11; IC 95%: 1,02-1,22). Veintinueve pacientes (48,3%; IC 95%: 35-60) presentaron sinovitis subclínica y no fueron clasificados como AR en remisión ecográfica. La adición de la información brindada por la presencia de tenosinovitis subclínica, permitió clasificar 6 pacientes más sin remisión ecográfica, arrojando un total de 35 pacientes (58,3%; IC 95%: 45-70) (p=0,272).

The aims were to evaluate prevalence of ultrasound (US) tenosynovitis in Rheumatoid Arthritis (RA) patients in sustained clinical remission, its association with disease features and to assess whether the presence of tenosynovitis could add information to synovitis to define ultrasound (US) remission. Sixty consecutive RA patients in sustained (≥12 months) clinical remission (DAS28 <2.6, CDAI <2.8 and/or SDAI <3.3) were included. All patients underwent US examination by the same experienced rheumatologist. The following were bilaterally assessed: 1st-6th extensor tendon compartments at wrist level, 2nd-5th finger flexor tendons, posterior tibial, peroneal tendons, wrists, 2nd-5th metacarpophalangeal and 2nd-5th proximal interphalangeal. US remission was defined as the absence of synovitis on gray scale (GS ≥2) and the absence of power doppler (PD) signal at both joint and tendon level. Grey scale ≥2 and PD tenosynovitis were detected in 14 (23%; 95% CI: 12-34) and 13 (21.7%; 95% CI: 10-32) RA patients in clinical remission, respectively. The most frequent involved tendons were: 6th extensor wrist compartment, 3rd finger flexor and posterior tibials. In multivariate analysis, the only feature associated with the presence of subclinical tenosynovitis was erythrosedimentation rate (ESR)(OR: 1.11; 1.02-1.22). Twenty-nine (48.3%; 95% CI: 35-60) patients had subclinical synovitis and were not classified as in US remission. Adding the information of subclinical tenosynovitis, 6 more patients would have been classified as not in US remission, yielding a total of 35 patients (58.3%; 95% CI: 45-70) (p=0.272).

Spotlight on certolizumab pegol in the treatment of axial spondyloarthritis: efficacy, safety and place in therapy.

Certolizumab pegol (CZP) is a pegylated humanized tumor necrosis factor-α inhibitor (TNFi) approved for the treatment of ankylosing spondylitis (AS) in the USA and for AS and non-radiographic axial spondyloarthritis (nr-axSpA) in Europe and in some Latin American countries. CZP lacks Fc region, preventing complement fixation and cytotoxicity mediated by antibody; CZP does not actively cross the placenta, unlike other TNFi. RAPID-axSpA study is a Phase III trial conducted in patients with AS and nr-axSpA as double blind and placebo controlled to week 24, dose blind to week 48 and open label to week 204. Of a total of 325 patients recruited, 107 patients were assigned to placebo and 218 patients to CZP (111 to CZP 200 mg Q2W, 107 to CZP 400 mg Q4W). Improvements in axial involvement, joint involvement, enthesitis and quality of life were reported in patients treated with CZP. Safety profile was like that reported for other TNFi in axSpA patients. In this article, we summarized the pharmacology and we reviewed the efficacy and tolerability of this drug for the treatment of axSpA. Some special considerations of CZP during pregnancy are included. CZP, the latest TNFi to be approved, showed efficacy in all manifestations of AS and nr-axSpA.

Psoriatic arthritis: new evidence for old concepts.

PURPOSE OF REVIEW: The review gives an updated overview of some of the new concepts in the management of psoriatic arthritis (PsA): early diagnosis, remission as an objective, treat-to-target, and treatment guidelines. RECENT FINDINGS: Early diagnosis, targeting remission as part of a treatment strategy, and new guidelines providing evidence-based support to these concepts are main topics in recent publications. SUMMARY: Dermatologists and rheumatologists should work together to reduce the number of patients remaining undiagnosed, and the time to do so.Remission definition in PsA is still controversial. There is good evidence and convincing arguments for both multidimensional measures, such as minimal disease activity, or unidimensional ones, as disease activity index for PsA. New data on the analysis of tight control of inflammation in early PsA trial showed that the strategy might not be cost-effective on the short term, and that oligoarthritis is less benefited.The new European League Against Rheumatism and Group for Research and Assessment of Psoriasis and PsA recommendations exhibit differences. Methotrexate and tumor necrosis factor inhibitors are favored in European League Against Rheumatism guidelines, whereas other conventional synthetic disease-modifying antirheumatic drugs and biologics are equally positioned in Group for Research and Assessment of Psoriasis and PsA recommendations.

The value of power Doppler ultrasound in patients with rheumatoid arthritis in clinical remission: Reclassifying disease activity? / Valor de la ecografía con Doppler de poder en pacientes con artritis reumatoide en remisión clínica: ¿reclasificación de la actividad de la enfermedad?

OBJECTIVES: The aim of the present study was to describe the ultrasound (US) findings in patients with rheumatoid arthritis (RA) in clinical remission, and to evaluate the ability of power Doppler (PD) US to reclassify disease activity in these patients. MATERIAL AND METHODS: We included consecutive patients with RA according to 2010 American College of Rheumatology/European League Against Rheumatism criteria, who were in clinical remission by the Disease Activity Score (DAS28<2.6). Twenty joints of both hands were assessed by US. PD signal was evaluated on a semi-quantitative scale from 0 to 3. Three different US-modified DAS28 (US-DAS28) were constructed, replacing the clinical swollen joint count by the PD US joint count using PD score ≥1, ≥2 or ≥3, respectively. RESULTS: Eighty-six patients were included. Twenty-three (26.7%) patients had at least one joint with abnormal US-positive PD signal. Thirteen percent of patients were reclassified to low disease activity by applying the US-DAS28 when joints were considered active with a PD signal ≥1; 12%, when a PD signal ≥2 was considered, and 2% of the patients were reclassified when a PD score of 3 was considered. No patients were reclassified to a level of moderate or high activity applying US-DAS28. CONCLUSIONS: Although around a quarter of patients with RA in clinical remission showed PD US features indicating residual activity, only a small percentage were reclassified to a state of low activity and none to a level of moderate or high activity, applying the proposed US-DAS28.

Ultrasound entheseal abnormalities at the distal interphalangeal joints and clinical nail involvement in patients with psoriasis and psoriatic arthritis, supporting the nail-enthesitis theory.

OBJECTIVE: It has been shown that nail involvement in psoriasis is associated with systemic enthesopathy. Our objective was to evaluate the association of nail involvement and enthesopathy at distal interphalangeal joint (DIP) level in psoriasis (PsO) and psoriatic arthritis (PsA) patients. METHODS: Consecutive patients (54 PsO and 56 PsA) seen at the outpatients clinic in this cross-sectional study were included. All patients underwent both clinical and ultrasound (US) assessment on the same day. RESULTS: US revealed enthesopathy in at least 1 DIP joint in 9 patients with PsO (17%, 95% CI: 8-29%) and in 18 patients with PsA (32%, 95% CI: 20-46%). US extensor tendon enthesopathy was detected in a higher proportion of fingers with clinical nail involvement compared with fingers without clinical nail involvement, both in PsO and PsA patients (61.2% vs 16.8%, p < 0.0001 and 60.1% vs 22%, p < 0.0001, respectively). Among patients with PsO, 20% (95% CI: 7-41%) and 14% (95% CI: 4-32%) of those with and without clinical nail involvement showed enthesopathy on US examination, respectively (p = 0.54). Among PsA patients, the prevalence of enthesopathy was 30% (95% CI: 15-49%) for patients with clinical nail involvement and 35% (95% CI: 17-56%) for those without nail involvement (p = 0.71). CONCLUSION: Nail disease was associated with DIP US enthesopathy. There was a significant increased prevalence of extensor tendon enthesopathy in fingers with involved nails both in PsO and PsA, although no association was found between nail involvement and extensor tendon enthesopathy at patients' level. These features might support the nail-entheseal pathogenesis theory at DIP level.