Prevalence and incidence of uveitis in patients with spondyloarthritis: the impact of the biologics era. Data from International ASAS-COMOSPA Study.

OBJECTIVES: Uveitis is a common extra-musculoskeletal manifestation in Spondyloarthritis (SpA). The aim of this study was to analyze the prevalence of uveitis in SpA patients, its association with geographical areas and to determine whether its incidence was different before and after the biological era. METHODS: ASAS-COMOSPA is a retrospective study that includes patients fulfilling ASAS SpA classification criteria from 22 countries. The overall prevalence of uveitis was calculated, and factors associated with the onset of a first episode of uveitis were evaluated using a Cox regression. A Log-Rank test was performed to compare the new onset of uveitis in the no biological era (SpA onset before 2000) vs biological era (SpA onset after 2000). RESULTS: 3984 patients were included. The likelihood of presenting a first uveitis episode increased over time, from a prevalence of 10.5% (95%CI 9.5%-11.4%) at the time of the SpA diagnosis to 46.6% (41.6%-51.5%) after 30 years since the SpA diagnosis. HLA-B27 positivity, family history of uveitis, peripheral enthesitis and IBD were associated with higher risk of uveitis. Patients with SpA disease onset after year 2000 showed a lower prevalence of uveitis compared with disease onset before year 2000 (8.2% vs 25.5%, p< 0.01), as well as a lower incidence (2.8 per 100 PY vs 6.1 per 100 PY, respectively). CONCLUSION: In our study the risk of having suffered from at least one episode of uveitis ranged from 10% at the time of the diagnosis of axSpA to 47% after 30 years of disease duration. Patients with disease onset after biologic therapy introduction showed a significantly lower prevalence and incidence of first episodes of uveitis.

Gender differences among patients with primary ankylosing spondylitis and spondylitis associated with psoriasis and inflammatory bowel disease in an iberoamerican spondyloarthritis cohort.

The aim of the study was to compare clinical manifestations, disease activity, functional capacity, spinal mobility, and radiological findings between men and women from a multicenter, multiethnic Ibero-American cohort of patients with Spondyloarthritis (SpA).This observational cross-section study included 1264 consecutive SpA patients who fulfilled the modified New York criteria for ankylosing spondylitis (AS). Demographic, clinical, and radiologic data were evaluated. Categorical data were compared by X or Fisher's exact tests and continuous variables by ANOVA with post-hoc tests.Primary AS was diagnosed in 1072 patients, psoriatic spondylitis in 147, and spondylitis associated to inflammatory bowel disease (IBD) in 45 patients. Overall, male patients were significantly younger, had longer diagnostic delay, lower disease activity, worse spinal mobility, better quality of life, and more severe radiologic damage. Dactylitis and enthesitis, as well as swollen joint count, were significantly more common among women. In primary AS, there was a marked male predominance (76.2%). Among patients with psoriatic spondylitis, male predominance was lower (57.8%), but was also associated with worse spinal mobility and more severe radiologic damage. In the total population, male patients with primary AS referred higher permanent work disability (13.2% vs 6.9%; P < 0.05), although no difference was observed in psoriatic or IBD spondylitis according to the gender.Among Ibero-American SpA patients, there are some differences in clinical and radiological manifestations, men showing more structural damage, whereas women more active disease. These data suggest that the phenotype of SpA differs between genders. This can influence the subsequent diagnostic approach and therapeutic decisions.

Secukinumab: a promising therapeutic option in spondyloarthritis.

Psoriatic arthritis (PsA) is the second most common chronic inflammatory joint disease. Ankylosing spondylitis (AS) is another less common but equally chronic and disabling spondyloarthritis (SpA). Therapeutic agents for the treatment of these diseases have been somewhat lacking as compared with those available for rheumatoid arthritis, which represents a significant challenge for both the treating physician and the pharmaceutical industry. A promising development for our understanding of the physiopathology of PsA and AS involves new targets to interrupt IL-17 and IL-12/IL-23 pathways. Up to 30-40 % of SpA patients have inadequate or poor response, or are intolerant to anti-TNF therapies. Therefore, there has been a clear unmet medical need in an important group of these patients. As a result, new therapeutic targets have emerged for the treatment of both axial and peripheral SpA. Interleukin 17 (IL-17) is a pro-inflammatory cytokine that is increased in psoriatic lesions as well as in the synovial fluid of patients with PsA and in sites of enthesitis in SpA. IL-23 has been shown to play an important role in the polarization of CD4+ T-cells to become IL-17 producers. Based on these evidences, blockade of the cytokine IL-17 or its receptors was considered to have therapeutic implications for the treatment of psoriasis, as well as PsA and AS.This article presents a thorough review of an IL-17 A blocking agent, its mechanism of action, its clinical efficacy and its therapeutic safety.

Rheumatic manifestations in inflammatory bowel diseases: a link between GI and rheumatology.

Musculoskeletal symptoms are the most frequent extra-intestinal manifestations of inflammatory bowel disease (IBD), ranging between 10 and 40 % of cases. Pathogenesis is still unclear, although several factors have been associated (genetic, environmental, and immunologic pathways). Rheumatic manifestations in IBD patients are heterogeneous, including axial and peripheral involvement, dactylitis, enthesitis, uveitis, as well as skin involvement. Currently, magnetic resonance imaging and ultrasonography are important tools for detecting early pathological changes in IBD patients with suspected rheumatic disease. New advances into the genetics and pathophysiology have provided more effective and targeted therapy for IBD patients with rheumatic manifestations. Given the high prevalence, awareness of the musculoskeletal symptoms is essential to avoid a misdiagnosis. Finally, an interdisciplinary approach of IBD patients, including rheumatologist and gastroenterologist, will improve the quality of life these patients.

Adherencia al tratamiento de pacientes con artritis reumatoidea que reciben medicamentos biológicos / Treatment adherence in patients with rheumatoid arthritis receiving biologics

Introducción: Al igual que en otras enfermedades crónicas, la adherencia al régimen terapéutico de los pacientes con artritis reumatoidea (AR) es baja (entre 30 y 80%), dependiendo de la definición de adherencia y de la metodología empleada para medirla. En este estudio se propone determinar el nivel de adherencia al tratamiento en pacientes con AR que reciben DMAR biológicas e identificar factores asociados a la falta de cumplimiento a la terapia. Material y métodos: Se realizó un estudio analítico, observacional de corte transversal en donde se incluyeron pacientes consecutivos con AR según criterios de clasificación (ACR’87) que se encontraban recibiendo fármacos biológicos para el tratamiento de su enfermedad en los últimos seis meses y que asistieron a la consulta ambulatoria. Para la valoración de la adherencia a DMAR se utilizaron los cuestionarios CQR (Compliance Questionnaire on Rheumatology) y el cuestionario SMAQ (Simplified Medication Adherence Questionnaire). Resultados: Se encuestaron 345 pacientes. Mediante el cuestionario SMAQ se observó una adherencia del 50% (159 pacientes). El Cuestionario CQR tuvo un puntaje mediano de 78 puntos (RIC 67-86). El 47% (147 pacientes) fueron adherentes (CQR >80). Sobre los pacientes incluidos, 151 (48%) refirieron no haber tenido ningún retraso, pérdida o adelanto de la dosis del biológico en los últimos 6 meses de tratamiento. El 52% no adherentes tuvo como causas: 146 (46%) pérdida de al menos una dosis del biológico con una mediana de dosis perdidas de 2 (RIQ: 1-3); 117 (37%) tuvo al menos un retraso en las dosis del biológico y 8 (2%) delantó la dosis. Los factores asociados al no cumplimiento de la terapia biológica fueron el tipo de cobertura médica, que el paciente no haya notado mejoría y la esperanza de una rápida respuesta al tratamiento, y la falta de adherencia a DMAR

Introduction: As in other chronic diseases, adherence to the therapeutic regimen of patients with rheumatoid arthritis (RA) is low (between 30 and 80%), depending on the definition of adherence and the methodology used to measure it. This study aims to determine the level of adherence to treatment in patients with RA who receive biological DMARs and to identify factors associated with non-compliance with therapy. MATERIAL AND METHODS: An observational, cross-sectional, observational study was performed in which consecutive patients with RA according to classification criteria (ACR'87) who were receiving biological drugs for the treatment of their disease in the last six months were included Attended the outpatient appointment. The CQR (Compliance Questionnaire on Rheumatology) and SMAQ (Simplified Medication Adherence Questionnaire) questionnaires were used to assess adherence to DMAR. Results: A total of 345 patients were surveyed. A 50% adherence (159 patients) was observed through the SMAQ questionnaire. The CQR Questionnaire had a median score of 78 points (RIC 67-86). 47% (147 patients) were adherent (CQR> 80). Regarding the patients included, 151 (48%) reported not having had any delay, loss or advancement of the biological dose in the last 6 months of treatment. The 52% of non-adherents had as causes: 146 (46%) loss of at least one dose of the biological with a median of doses lost of 2 (RIQ: 1-3); 117 (37%) had at least one biological dose delay and 8 (2%) delayed the dose. Factors associated with non-compliance with biological therapy were the type of medical coverage, the patient's perceived improvement and the expectation of a rapid response to treatment, and lack of adherence to DMAR.

A simplified version of Ankylosing Spondylitis Disease Activity Score (ASDAS) in patients with ankylosing spondylitis.

This study aimed to develop a simplified version of the Ankylosing Spondylitis Disease Activity Score (ASDAS). The study included consecutive patients with ankylosing spondylitis according to modified New York and/or Assessment in Ankylosing Spondylitis 2009 criteria. Sociodemographic data and characteristics of the disease (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Ankylosing Spondylitis Quality of Life (ASQoL)) and erythrocyte sedimentation rate (ESR) were collected. ASDAS simplified version (SASDAS) was calculated as the simple linear sum of the five components of ASDAS which include: patient global assessment using visual analogue scale, back pain (BASDAI question no. 2), peripheral pain and swelling (BASDAI question no. 3), morning stiffness (BASDAI question no. 6), and ESR in millimeters per hour, divided by 10 so as to make it equivalent to the other scale's components. Eighty-six patients were included: 69 (80.2 %) were men with a median age of 46 years and median disease duration of 19 years. SASDAS showed an excellent correlation with the ASDAS (r = 0.93). SASDAS also showed a good correlation with night pain (r = 0.60), global pain (r = 0.69), ASQoL (r = 0.70), BASFI (r = 0.75), and BASDAI (r = 0.96). Using ASDAS cut-off values previously suggested, the corresponding cut-off values for SASDAS were as follows: from 0 to 7.8 (inactive disease), from 7.9 to 13.8 (moderate disease activity), from 13.9 to 27.6 (high disease activity), and above 27.6 (very high disease activity) with optimum sensitivity and specificity. SASDAS showed an excellent correlation with conventional clinical measures of disease activity, and it can be easily calculated and is simple to use in daily clinical practice.

Riesgo cardiovascular en una cohorte de pacientes con espondilitis anquilosante / Cardiovascular risk in patients with ankylosing spondylitis

Objetivos: Determinar la prevalencia de factores de riesgo y enfermedad cardiovascular en pacientes con EA, estimar el riesgo cardiovascular a 10 años a través del score de Framingham/ATPIII y evaluar la asociación entre actividad inflamatoria de la enfermedad y el riesgo de un evento cardiovascular. Métodos: Se incluyeron pacientes consecutivos con diagnóstico de EA según criterios de New York modificados. Se consignaron datos sobre factores de riesgo cardiovascular, evaluación clinimétrica, índice de actividad medida por BASDAI y tratamiento farmacológico. Se utilizó el score de Framingham/ATPIII para estimar el riesgo cardiovascular a 10 años. Resultados: Se evaluaron 44 pacientes con EA y 44 controles, con una edad mediana de 38,5 años, 86,4% varones. Los pacientes tuvieron una mediana de índice de BASDAI de 3,8 (RIC 2,10-5,81). La frecuencia de factores de riesgo cardiovascular y marcadores de inflamación fue similar en ambos grupos. La enfermedad cardiovascular fue más frecuente en el grupo con EA (13,6% vs. 2,3%, p= 0,11). No hubo diferencia en el riesgo cardiovascular estimado a 10 años entre pacientes y controles. La actividad de la enfermedad no se asoció con mayor riesgo cardiovascular. Conclusión: Los pacientes con EA tienen mayor frecuencia de enfermedad cardiovascular y su riesgo puede estar asociado con factores diferentes a los observados en la población general.

Objectives: To estimate the prevalence of cardiovascular risk factorsand cardiovascular disease in patients with AS; to determine the 10 yearcardiovascular risk by Framingham/ATPIII score, and to establish an associationbetween disease activity and increased cardiovascular risk.Methods: Consecutive patients with AS diagnosed by the modifiedNew York classification criteria were included. Data about cardiovascularrisk factors, clinimetry, BASDAI activity score and pharmacologicaltreatment were registered.Results: 44 patients and 44 controls were included, with a medianage of 38.5 years, 86.4% were men. BASDAI score was 3.85 (IQR0-8). Patients and controls had similar frequency of cardiovascularrisk factors and inflammatory markers. Cardiovascular disease wasmore frequent in AS patients (13.6% vs. 2.3%, p = 0.11). No differencewas found in the estimated cardiovascular risk at 10 yearsbetween patients and controls. Disease activity did not associate withan increased cardiovascular risk.Conclusion: Patients with AS have more cardiovascular disease andthe risk may be associated with factors different than those observedin the general population.

Differential features between primary ankylosing spondylitis and spondylitis associated with psoriasis and inflammatory bowel disease.

OBJECTIVE: To describe differential characteristics of axial involvement in ankylosing spondylitis (AS) as compared with that seen in psoriatic arthritis (PsA) and inflammatory bowel disease (IBD) in a cohort of Ibero-American patients. METHODS: This study included 2044 consecutive patients with spondyloarthritis (SpA; ESSG criteria). Demographic, clinical, disease activity, functional ability, quality of life, work status, radiologic, and therapeutic data were evaluated and collected by RESPONDIA members from different Ibero-American countries between June and December 2006. Patients selected for analysis met modified New York criteria (mNY) for AS. RESULTS: A total of 1264 patients met the New York criteria for AS: 1072 had primary AS, 147 had psoriatic, and 45 had IBD-associated spondylitis. Median disease duration was comparable among the 3 patient groups. Patients with primary AS were significantly younger (p = 0.01) and presented a higher frequency of males (p = 0.01) than the other 2 groups. Axial manifestations such as inflammatory back pain and sacroiliac pain were significantly more frequent in patients with primary AS (p = 0.05) versus other groups, whereas frequency of dactylitis, enthesitis, and peripheral arthritis was more common in patients with psoriatic spondylitis (p = 0.05). Spinal mobility was significantly more limited in patients with primary AS versus the other 2 groups (p = 0.0001). Radiologic changes according to BASRI total score were equally significant in primary AS. Disease activity (BASDAI), functional ability (BASFI), and quality of life (ASQoL) scores were comparable in the 3 groups. CONCLUSION: Patients with primary AS had more severe axial involvement than those with spondylitis associated with psoriasis or IBD. Functional capacity, disease activity, and quality of life were comparable among the groups studied.

Epidemiology of spondyloarthritis in Argentina.

INTRODUCTION: Spondyloarthritis (SpA) includes a group of diseases that share immunogenetic, clinical and radiologic findings, with a particular involvement of the axial skeleton and the entheses. METHODS: SpA patients attending ambulatory care in 11 rheumatology services located in 6 Argentine provinces were included in a prospective, observational multicentre cohort of SpA in Argentina (Iberoamerican Spondyloarthritis Registry [RESPONDIA]). Data collected were transmitted online and stored in the Spanish spondyloarthritis registry (REGISPONSER) Web site. Sociodemographic, clinical features and diagnosis, disease activity, functional status, quality of life, work status, radiographic changes and treatment data were collected by means of validated tools. RESULTS: A total of 402 patients were included; 59% were male, with median age of 48.3 years and median disease duration of 8 years; 68.7% of patients belonged to middle and lower-middle social classes. Eighty-six patients were diagnosed with ankylosing spondylitis (AS), 242 with psoriatic arthritis, 25 with reactive arthritis, 10 with SpA associated with inflammatory bowel disease, 33 with undifferentiated SpA and 6 with juvenile AS. The median score was 2.6 for the Bath AS Functional Index, 3.8 for the Bath AS Disease Activity Index and 5 for the Bath AS Radiology Index. The lower social class patients achieved a worse Bath AS Functional Index than other social classes and a worse Bath AS Disease Activity Index, compared with upper-middle class. CONCLUSIONS: The sociodemographic distribution pattern observed in these SpA patients was similar to that expected in the general population of Argentina, with worse functional capacity and higher disease activity observed in the lower social classes.

General characteristics of an early arthritis cohort in Argentina.

OBJECTIVE: The aim of the present study is to describe the general characteristics of a cohort of patients with early arthritis in Argentina. METHODS: CONAART (Consorcio Argentino de Artritis Temprana--Argentine Consortium for Early Arthritis) is an initiative of seven rheumatology centres across Argentina. Patients were included if they had at least one or more swollen joints and <2 years of disease duration. Social, demographic, familiar, hereditary, clinical and laboratory data were recollected. At first visit and every year, X-rays of hands and feet were performed and working characteristics and pharmaco-economic data were re-collected. RESULTS: A total of 413 patients were included. Of them, 327 (79.2%) were women with a median age of 49 years and a median disease duration of 6 months. Of the total, 183 (44.3%) had RA (ACR 1987) and 167 (40.4%) undifferentiated arthritis (UA). Other diagnoses included: 12 crystalics, 11 PsA, 6 uSpA, 6 other CTD, 1 AS and 27 other diagnosis. As 85% of our population had RA and UA, we only compared these two groups of patients. Patients with RA had significantly worse activity parameters of the disease (DAS of 28 joints), functional capacity (HAQ) and quality of life (Rheumatoid Arthritis Quality of Life) than patients with UA. The frequency of RF and anti-CCP, and symmetrical distribution were also significantly higher in patients with RA compared with UA patients. All patients with RA initiated early specific treatment, in a period no longer than 6 months from the beginning of the disease. CONCLUSION: Early arthritis clinics are a useful tool to identify and treat patients with different forms of joint involvement.

Validación del cuestionario RAPID3 en una cohorte de pacientes con artritis reumatoidea temprana y establecida, y su correlación con otros índices de actividad / Validation of RAPID3 questionnaire in a cohort of patients with early and established rheumatoid arthritis and its correlation with other activity indices

Introducción: El RAPID3 es un índice de actividad que incluye tres medidasauto-reportadas por el paciente: la función física, el dolor y la evaluación global de la enfermedad por el paciente. Objetivos: Validar el cuestionario RAPID3 en pacientes con AR temprana y establecida, evaluar su correlación con otros índices de actividad y medidas de evaluación y determinar el tiempo en completar y calcular el cuestionario.Métodos: Se incluyeron pacientes con diagnóstico de AR temprana (<2 años de evolución) y establecida. Todos los pacientes completaron HAQ-A, RAPID3 y RAQoL. Se determinó evaluación global de la enfermedad por el paciente y el médico por EVA. Se midió ERS el día de la visita. Se calculó DAS28, CDAI e IAS. Se cronometró el tiempo en completar y calcular el cuestionario. Resultados: Se evaluaron 112 pacientes. RAPID3 presentó un buena correlación con DAS28 (r=0,60), CDAI (r=0,60) e IAS (r=0,62) y una muy buena correlación con HAQ-A (r=0,83) y RAQoL (r=0,75). La mediana en completar el cuestionario fue de 139 segundos y la mediana en calcularlo fue de 11 segundos. Discusión: RAPID3 es un cuestionario válido, sencillo, fácil de completar y de rápido cálculo. Presentó una buena correlación con otros índices de actividad como así también con HAQ-A y RAQoL.

Validación y adaptación cultural de una versión argentina del cuestionario para calidad de vida PsAQoL en pacientes con artritis psoriática / Validation and cultural adaptation of an Argentine version of the Psoriatic Arthritis Qualiy of Life (PsAQoL) Questionnaire

Objetivos: El objetivo de nuestro estudio fue desarrollar una versión argentina del cuestionario PsAQoL adaptada del inglés, con el fin de validar su uso en los pacientes con APs de nuestro país. Resultados: Se evaluaron 31 pacientes con diagnóstico de APs, 64% mujeres, con una mediana de edad de 52 años (RIC 39-60), y una mediana de tiempo de evolución de la artritis de 9 años (RIC 4-17). La reproducibilidad del PsAQoL fue excelente, con un CCI de 0,99 (IC 95% 0,98-0,99). No se hallaron preguntas redundantes en la Correlación Interítem. La confiabilidad según alfa de Cronbach fue de 0,75. La mediana de tiempo de respuesta fue de 195 segundos (RIC 153-222) y más del 70% de los pacientes entendió el 100% de las preguntas. El PsAQoL mostró una buena correlación con HAQ (r=0,85), DAS28 (r=0,7), EVA de dolor (r=0,66), EVA de actividad por paciente (r=0,61), EVA de fatiga (r=0,74) y Escala de Salud de EuroQoL (r=-0,83). No se observó correlación con las medidas de compromiso cutáneo (PASI, EVA de piel). En el modelo de regresión lineal, la principal variable asociada a calidad de vida fue el HAQ (coef. β=0,74, p=0,0001) seguida por EVA de dolor (coef. β=0,19) y EVA de piel (coef. β=0,10). Conclusiones: Nuestra versión argentina del PsAQoL demostró aceptabilidad, confiabilidad y reproducibilidad en nuestros pacientes con APs. Estos resultados validan esta versión adaptada al castellano, facilitando su implementación en futuros estudios.

Factors associated with disability in patients with rheumatoid arthritis.

OBJECTIVE: Analyze disability determinants in a cohort of Argentine patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: Consecutive patients with RA, according to ACR'87 criteria, were recruited from 6 rheumatology centers. Demographic and socioeconomic data, family history, comorbid diseases, extra-articular manifestations and information about received treatments were provided. Disease activity was assessed using Disease Activity Score 28 (DAS 28) and the Health Assessment Questionnaire (HAQ)-A was used for the functional capacity. Hand and feet radiographs were assessed using Sharp-van der Heijde score. RESULTS: A total of 640 patients with RA were included, of which 85.2% were females. Mean age was 53 years (interquartile range [IQR], 44-62) and mean disease duration was 8 years (IQR, 4-14). DAS 28 mean was 2.72 (IQR, 1.7-3.7) and HAQ-A mean was 0.62 (IQR, 0.13-1.25). Multiple linear regression showed that the main variables associated with disability were DAS 28, radiologic damage and age. Main predictors of functional disability in the multiple logistic regression using severe HAQ (>2) as dependent variable were DAS 28 (OR, 2; P < 0.0001); age (OR, 1; P = 0.008); and structural damage (OR, 1; P = 0.001). CONCLUSIONS: In this population, the disease activity was the variable that showed the highest impact on the physical function. Radiologic damage affected HAQ as the disease progressed.

Clinical and serologic characterization of an Argentine pediatric myositis cohort: identification of a novel autoantibody (anti-MJ) to a 142-kDa protein.

OBJECTIVE: Autoantibodies are frequently found in adult patients with polymyositis (PM), dermato-myositis (DM), and overlap myositis disorders. They are less common in pediatric patients with myositis. We investigated the autoantibody pattern in a pediatric Argentine Caucasian cohort to characterize novel autoantibodies. METHODS: Sera from children that satisfied published criteria for idiopathic inflammatory myopathy were analyzed for autoantibodies by RNA and protein immunoprecipitation and immunoblotting techniques. Routine myositis-specific and myositis-associated autoantibodies as well as autoantibody specificities were determined. RESULTS: We tested sera from 64 consecutive pediatric myositis patients, including 40 with juvenile DM, 7 with juvenile PM, and 17 with overlap myositis syndromes. Sixteen (25%) patients were found to have anti-MJ autoantibody exclusively, which appears to identify a subset of pediatric myositis patients with severe disease characterized by muscle contractures and atrophy and significant compromise of functional status. Fourteen (22%) patients were found to have an antibody targeting 2 proteins of 155 and 140 kDa. Other myositis-specific autoantibodies were uncommon in this pediatric cohort. CONCLUSION: A newly recognized autoantibody, anti-MJ, was the most common antibody found in this Argentine pediatric cohort. The clinical features indicated that this antibody is distinct from other reported antibodies in pediatric patients with myositis.

Caracterización inmunogenética de pacientes con espondilitis anquilosante en Argentina / Immunogenetic profile of ankylosing spondylitis in Argentina

Objetivo: Evaluar la influencia del polimorfismo genético del HLA clase I y II, TNF e IL1 en pacientes argentinos con espondilitis anquilosante (EA). Material y métodos: Este fue un estudio de asociación en el que se incluyeron pacientes con EA clasificados de acuerdo a los criterios de New York modificados. Se registraron datos demográficos y clínicos de la enfermedad. Un grupo no relacionado, pero pareado, de 154 personas fue utilizado como grupo control. La genotipificaciónfue realizada utilizando técnicas basadas en la reacción en cadena de la polimerasa. Se evaluaron alelos HLA clase I (A y B) y II (DR), polimorfismos de nucleótido simples del TNF (-238 y 308) y del gen IL1 (-511 y +3954). Resultados: Se incluyeron 52 pacientes con EA, de los cuales 90,4% fueron varones, con una edad mediana de 44 años rango intercuartilo (RIQ) 34-53. Confirmamos la asociación del HLA-B27 con la enfermedad (90,4% vs. 5,2%, con OR: 171,5, p = 1x10-30). El subtipo más frecuente tanto en pacientes como en controles fue el B27*05 (85%). La comparación de alelos de clase A y B no B27 entre controles y pacientes no mostró diferencias significativas. La comparación entre los alelos clase II evidenció una mayor frecuencia del HLA-DR1 (59,6% vs. 20%, OR: 6,1, p = 1x10-5). El genotipo TNF -308 GA fue un factor de riesgo (94% vs. 81%, OR: 3,96, p = 0,02), mientras que el genotipo -238 GA fue protector (53% vs. 76%, OR: 0,19, p >0,0001). El alelo IL1β-511C se asoció con la EA (66% vs. 53%, OR: 1,74, p = 0,03). Conclusión: En el presente estudio, hemos replicado por primera vez en la población argentina la influencia del HLA, TNF e IL1 ;en la EA. Estos hallazgos permiten una comprensión homogénea de la fisiopatogenia de la enfermedad.

Objective: To determine the influence of the genetic polymorphismof HLA class I and II, TNFα and IL1β in Argentinean patients withankylosing spondylitis. Material and Methods: This was an association study where AS patients according to modified New York criteria were included. Werecorded demographic and clinical data of the disease. A non related but age and sex matched group of 154 people was used as controls. Genotyping was performed using polymerase chain reaction (PCR) techniques. We evaluated HLA class I (A and B) and class II (DR), single nucleotide polymorphism of the TNFα (-238 and 308) and IL1β (-511 and +3954). Results: We included 52 patients with AS of whom 90.4% were male with a median age of 44 years (IQR 34-53). We confirm the association of HLA-B27 with disease (90.4% vs 5.2%. OR 171.5, p= 1x10-30). The most common subtype in both patients and controls was B27*05 (85%). Comparison between class A and B alleles non B27 between controls and patients did not show significant differences. Comparison between class II alleles showed a statistically significant higher frequency of HLA-DR1 in AS patients (59.6% vs.20% OR 6.1, p = 1x10-5). TNF -308 GA genotype was a risk factor for AS (94% vs. 81% OR 3.96 p = 0.02), while the -238 GA genotype had a protective effect and was more frequently observed in controls (76% vs. 53%, OR 0.19, p >0.0001). IL1β -511 allele wasassociated with a higher susceptibility to AS (66% vs. 53%, OR 1.74 p = 0.03).Conclusion: In the present study, we have replicated for the first time in the Argentinean population, the influence of HLA, TNFα, and IL1β in patients with AS. These findings allow a uniform understanding of the physiopathology of the disease.

Childhood systemic lupus erythematosus in Latin America. The GLADEL experience in 230 children.

To evaluate disease characteristics of childhood onset SLE in Latin America and to compare this information with an adult population in the same cohort of GLADEL. A protocol was designed as a multicenter, multinational, inception cohort of lupus patients to evaluate demographic, clinical, laboratory and serological variables, as well as classification criteria, disease activity, organ damage and mortality. Descriptive statistics, chi square, Fisher's exact test, Student's t test and multiple logistic regression were used to compare childhood and adult onset SLE. 230 patients were <18 years and 884 were adult SLE patients. Malar rash, fever, oral ulcers, thrombocytopenia and hemolytic anemia and some neurologic manifestations were more prevalent in children (p<0.05). On the other hand, myalgias, Sjögren's syndrome and cranial nerve involvement were more frequently seen in adults (p<0.05). Afro-Latin-American children had a higher prevalence of fever, thrombocytopenia and hemolytic anemia. White and mestizo children had a higher prevalence of malar rash. Mestizo children had a higher prevalence of cerebrovascular disease and cranial nerve involvement. Children met SLE ACR criteria earlier with higher mean values than adults (p: 0.001). They also had higher disease activity scores (p: 0.01), whereas adults had greater disease damage (p: 0.02). In Latin America, childhood onset SLE seems to be a more severe disease than adults. Some differences can be detected among ethnic groups.

Anti-20S proteasome antibodies in psoriatic arthritis.

OBJECTIVE: Proteasomes are targets of humoral autoimmune response in patients with connective tissue diseases and other organ-specific autoimmune diseases. The finding of circulating proteasomes in psoriasis, the multiplicity of mechanisms regulated by proteasomes that are also implicated in the pathogenesis of psoriatic arthritis (PsA), and the increasing evidence linking PsA and autoimmunity led us to evaluate whether the 20S proteasome represents an antibody target in PsA. METHODS: Serum samples from 36 patients with PsA and 30 age- and sex-matched healthy subjects were tested for the presence of anti-20S proteasome antibodies (anti-20S antibody). Additional controls included 24 patients with systemic lupus erythematosus (SLE) and 20 with rheumatoid arthritis (RA). The associations of anti-20S antibodies with clinical, laboratory, and therapeutic measures were evaluated. RESULTS: 27.8% of the PsA patients were positive for anti-20S antibody compared to 41.6% of the SLE group and 5% of the RA group. None of the healthy subjects were seropositive for anti-20S antibody. In PsA, anti-20S seropositivity was not associated with the presence of other autoantibodies or with a particular subgroup of articular involvement. CONCLUSION: Immunoreactivity against proteasomes occurs frequently in patients with PsA. This finding supports the concept of PsA as an autoimmune disease and opens new avenues for investigating its pathogenesis.

Indicación de terapia biológica en pacientes con enfermedades reumáticas de la consulta ambulatoria / Biologic treatment in patients with Rheumatic Diseases from the clinic

Introducción y objetivo: Determinar la proporción de pacientes que presentan indicación de tratamiento con terapia biológica y comparar las características demográficas y clínicas de los pacientes con y sin indicación y entre aquellos que reciben o no dicho tratamiento. Material y métodos: Se incluyeron pacientes consecutivos con diagnóstico de AR (ACR`87) y EASN (criterios europeos). Se recolectaron datos demográficos, socioeconómicos, clínicos, laboratorio. Se evaluó si los pacientes presentaban indicación de tratamiento con agentes anti-TNF, de acuerdo a guías de tratamiento (ASAS 2003 y SAR 2004) y/u opinión del evaluador. En pacientes con indicación y que no reciben actualmente se consignaron las causas de la misma. Resultados: Se incluyeron 200 pacientes, 182 AR y 18 EASN. De los 182 pacientes, el 44,5% presentan indicación de terapia biológica por guías de tratamiento y el 44% por opinión del evaluador. El 11% recibe actualmente tratamiento anti-TNF. El 16,5% de los pacientes que tenían indicación y no recibían tratamiento se encontraban entrámite y el 17% no tenía indicación por parte del profesional. En el análisis de regresión logística, la presencia de mayor HAQ y DAS 28 fueron las variables con mayor fuerza de asociación entre los que reciben tratamiento biológico. Los 3 grupos que no recibían biológicos difirieron significativamente en la actividad de la enfermedad. Conclusiones: El 44% tiene indicación de terapia biológica, pero sólo el 11% la recibe; las 2 principales causas son la falta de indicación por el médico y que se encuentra tramitando el mismo.