Significance of HLA-B[*]51 allele expression in Crohn's disease: a case-control study.

OBJECTIVES: Crohn's disease (CD) and Behçet's disease (BD) are two autoinflammatory diseases that share clinical and pathogenic features. Furthermore, when BD involves the gastrointestinal tract, it is extremely difficult to distinguish endoscopic lesions from CD lesions. HLA-B*51 allele expression is highly associated with BD diagnosis. In this study we analysed HLA-B*51 status in 70 Argentine patients with confirmed CD diagnosis and compared it to our previous Argentine BD cohort, with the aim of finding similarities or differences between these two diseases regarding HLA-B*51 status. METHODS: This is a multi-centre case-control study, including 70 patients with confirmed CD diagnosis, who underwent HLA-B*51 allele status testing; the results were compared to our previous BD cohort of 34 patients. RESULTS: Among patients with CD, 12.85% were positive for the HLA-B*51 allele, compared with 38.24% patients with BD (OR=0.238; 95% CI=0.089-0.637; p=0.004). CONCLUSIONS: Our finding suggests that determination of HLA-B*51 allele status may contribute to the differential diagnosis between CD and BD.

Validación del índice ReXSPA (Reductive X-ray Score for Psoriatic Arthritis) en pacientes con Artritis Psoriásica de la cohorte RAPSODIA / Validation of the ReXSPA index (Reductive X-ray Score for Psoriatic Arthritis) in patients with Psoriatic arthritis of the RAPSODIA cohort

Existen diversos índices capaces de valorar el daño radiográfico en pacientes con artritis psoriásica (APs), sin embargo la mayoría fueron creados para su uso en Artritis Reumatoidea y luego modificados para APs, por lo tanto no valoran lesiones características como la osteoproliferación. El objetivo de este estudio fue validar el Reductive X-Ray Score for Psoriatic Arthritis (ReXSPA), el cual fue recientemente desarrollado para su uso en cohortes observacionales. Material y métodos: Estudio de corte transversal, en el cual se incluyeron pacientes ≥18 años de edad, en forma consecutiva, con diagnóstico de APs según criterios CASPAR. A todos los pacientes se les realizaron radiografías de manos y pies en proyección anteroposterior. Dos lectores ciegos para las características clínicas de los pacientes y previamente entrenados, analizaron las mismas por medio de los índices Sharp van der Heijde modificado para APs (SvdHmAPs) y ReXSPA. Se midió el tiempo empleado para la lectura de los índices radiográficos y para el cálculo de los mismos. Resultados: Se incluyeron 66 pacientes, 50% mujeres, con tiempo de evolución de la APs mediano de 8 años (RIC: 4-14.3). 132 radiografías fueron evaluadas según los índices SvdHmAPs [m 35 (RIC: 16.3-72.5)] y el ReXSPA [m 22 (RIC: 7-46.3)]. El tiempo para la lectura radiográfica fue significativamente menor para ReXSPA comparado con SvdHmAPs [media 5.8±2.1 vs media 7.5±2.5 minutos, p<0.0001], al igual que el tiempo para calcularlo [media 26.5±14.7 vs media 55.3±38.3 segundos, p<0.0001]. La correlación entre estos últimos fue excelente (Rho: 0.93). En el análisis multivariado se observó asociación de ambos índices con el tiempo de evolución de la enfermedad y en el caso de ReXSPA también con la edad. Conclusión: El índice ReXSPA ha demostrado validez y una excelente correlación con el índice SvdHmAPs, con menor tiempo para su lectura y cálculo. Evaluaciones longitudinales posteriores permitirán demostrar la validez de estos hallazgos.

There are many scores available to measure radiographic joint damage in patients with Psoriatic Arthritis (PsA), but most of them were developed for Rheumatoid Arhtritis and then modified for PsA. These scores do not evaluate juxtaarticular bone proliferation. The aim of our study was to validate the Reductive X-Ray Score for Psoriatic Arthritis (ReXSPA), which was recently developed to be used in observational cohorts. Methods: A cross-sectional study was carried out. Consecutive patients ≥18 years old with PsA according to CASPAR criteria were included. All patients underwent X-rays of the hands and feet in an anteroposterior view. Two blind readers for the clinical characteristics of the patients and previously trained, scored them by Sharp van der Heijde modified for PsA (PsA-SvdH) and ReXSPA indexes. Time to read and calculate both scores were measured. Results: A total of 66 patients were included, half of them were female, median (m) disease duration of 8 years (IQR: 4-14.3). 132 X-Rays were scored according to PsA-SvdH [m 35 (IQR: 16.3-72.5)] and ReXSPA [m 22 (IQR: 7-46.3)]. Time to read was significantly shorter for ReXSPA than PsA-SvdH [mean 5.8±2.1 vs mean 7.5±2.5 minutes, p<0.0001], as well as, time to calculate them [mean 26.5±14.7 vs mean 55.3±38.3 seconds, p<0.0001]. The correlation between both indexes was excellent (Rho: 0.93). In the multivariate analysis, using both radiographic scores as dependent variable, association of each of the indices with disease duration was observed, and ReXSPA also had association with age. Conclusion: The ReXSPA index has shown validity and a very good correlation with PsA-SvdH. It is quicker to read and to calculate than PsA-SvdH. Subsequent longitudinal evaluations will allow demonstrating the validity of these findings.

Rigidez matinal en artritis reumatoidea: su relevancia en la evaluación de la enfermedad / Morning stiffness and rheumatoid arthritis: its relevance in disease evaluation

En los últimos años, hemos visto importantes cambios en los criterios de clasificación, medidas de evaluación y pautas de tratamiento de la Artritis Reumatoidea (AR). Tanto los avances en el conocimiento fisiopatogénico de la enfermedad como los resultados a largo plazo de las cohortes de seguimiento longitudinales, han evidenciado la gravedad de la AR cuando ésta queda librada a su historia natural, viéndose esto reflejado en su potencial de progresión del daño articular y discapacidad, deterioro marcado de la calidad de vida y aumento de la mortalidad. Esa información pronóstica puso en evidencia la necesidad de un cambio de paradigma en el manejo de la enfermedad, apuntando principalmente a un diagnóstico temprano y a un tratamiento dirigido al objetivo, acompañado de un control estricto de la actividad inflamatoria. Este contexto exigió a su vez una revisión de las herramientas necesarias para diagnosticarla precozmente y evaluar adecuadamente la actividad, permitiendo los ajustes necesarios del tratamiento en búsqueda de remisión o baja actividad de la enfermedad

Is ankle involvement underestimated in rheumatoid arthritis? Results of a multicenter ultrasound study.

The aim of this study is to investigate the prevalence of subclinical ankle involvement by ultrasound in patients with rheumatoid arthritis (RA). The study was conducted on 216 patients with RA and 200 healthy sex- and age-matched controls. Patients with no history or clinical evidence of ankle involvement underwent US examination. For each ankle, tibio-talar (TT) joint, tibialis anterior (TA) tendon, extensor halux (EH) and extensor common (EC) tendons, tibialis posterior (TP) tendon, flexor common (FC) tendon and flexor hallux (FH) tendon, peroneous brevis (PB) and longus (PL) tendons, Achilles tendon (AT) and plantar fascia (PF) were assessed. The following abnormalities were recorded: synovitis, tenosynovitis, bursitis, enthesopathy and rupture. BMI, DAS28, RF ESR and CRP were also obtained. A total of 432 ankles of patients with RA and 400 ankles of healthy controls were assessed. In 188 (87%) patients with RA, US showed ankle abnormalities whereas, in control group, US found abnormalities in 57 (28.5 %) subjects (p = 0.01). The most frequent US abnormality in RA patients was TP tenosynovits (69/216) (31.9 %), followed by PL tenosynovitis (58/216) (26.9 %), TT synovitis (54/216) (25 %), PB tenosynovitis (51/216) (23.6 %), AT enthesopathy (41/216) (19 %) and AT bursitis (22/216) (10.2 %). In 118 RA patients out of 216 (54.6%), a positive PD was found. No statistically significant correlation was found between the US findings and age, disease duration, BMI, DAS28, RF, ESR and CRP. The present study provides evidence of the higher prevalence of subclinical ankle involvement in RA patients than in age- and gender-matched healthy controls identified by US.

The -308 G/A polymorphism in the tumor necrosis factor-α gene is not associated with development and progression of rheumatoid arthritis in Argentinean patients.

AIM: A polymorphism in the tumor necrosis factor-alpha (TNF-α) promoter region has been associated with disease susceptibility and progression in rheumatoid arthritis (RA). The presence of an adenosine (TNF2 allele) instead of a guanine (TNF1 allele) at position -308 may be responsible for a general increase in the transcriptional activity of the TNF-α gene. Our aim was to evaluate the association of the TNF2 allele with the risk of disease development and/or progression of RA in an Argentine population cohort. METHODS: Two hundred and twenty-three consecutive patients with RA according to the 1987 criteria of the American College of Rheumatology were included in the study. Clinical variables, Disease Activity Score 28, Health Assessment Questionnaire and Rheumatoid Arthritis Quality of Life were recorded. The radiographic erosions were determined by the method of Sharp/van der Heijde. A group of 111 healthy subjects matched by sex and age was used as a control. All samples were genotyped for the -308 G/A TNF-α polymorphism. RESULTS: No significant differences were observed either in the frequency of the TNF2 allele or in the genotypic distributions of the -308 G/A TNF-α polymorphism (P > 0.05) between the control group and the RA patients. No association was found between the TNF2 allele and the variables related to the course and outcome of the disease (P > 0.05). CONCLUSION: In this cohort of Argentinean patients with RA, the TNF2 allele was neither associated with susceptibility to the disease nor was it associated with the variables related to the course and outcome of the disease.

Fatigue assessment and its impact in the quality of life of patients with ankylosing spondylitis.

The most frequently reported symptoms by patients with ankylosing spondylitis (AS) are pain, stiffness, and fatigue. Previous studies have estimated a 63% prevalence of fatigue in AS, with a low correlation of fatigue with pain and functional capacity. The objective of this study is to assess fatigue prevalence in AS patients and establish the main associated factors. A case-control study including AS patients according to New York modified criteria was carried out. The control group included individuals of the general population without rheumatic conditions, matched by gender, age, and socioeconomic level. Disease-related variables were recorded. Functional capacity, disease activity, and quality of life were assessed using Bath Ankylosing Spondylitis Funcional Index (BASFI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and ankylosing spondylitis quality of life (ASQoL). CES-D questionnaire was used to evaluate depression and fatigue severity scale (FSS) to evaluate fatigue. Sixty-four consecutive AS patients and 95 controls were included. Patients' median age was 44 years (interquartile range (IQR), 33.25-53), 89.1% were male, and had a median disease duration of 17 years (IQR, 10.3-25). Fatigue prevalence in AS was 73.4% compared to 30.5% in the control group (p < 0.001; OR, 2.08 (95% CI, 1.53-2.83)). Furthermore, fatigue in AS correlated with ASQoL (r = 0.65), BASFI (r = 0.52), BASDAI (r = 0.52), and depression (r = 0.51), whereas no correlation with age or disease duration was found. In the linear regression analysis using fatigue as the dependent variable, depression was the only associated variable (p = 0.01). No association with age, gender, disease duration, BASDAI, BASFI, or presence of comorbidities was found. Finally, BASDAI fatigue question correlated with the FSS (r = 0.55). Fatigue was significantly more prevalent in AS than in healthy controls. The main determinant factor of fatigue was the presence of depression, explaining 30% of its variability. Recognizing these factors could have important therapeutic implications.

Effects of cigarette smoking on early arthritis: a cross-sectional study-data from the Argentine Consortium for Early Arthritis (CONAART).

Our objective was to analyze the effects of cigarette smoking on disease activity, functional capacity, radiographic damage, serology and presence of extraarticular manifestations in patients with rheumatoid arthritis and undifferentiated arthritis. This is a cross-sectional study of 1,305 patients (729 with rheumatoid arthritis and 576 with undifferentiated arthritis) from CONAART, the Argentine Consortium for Early Arthritis that includes patients older than 16 years with <2 years of disease. Sociodemographic data, clinical characteristics of the disease and smoking history were collected. In patients with rheumatoid arthritis the disease activity score of 28 joints was 5.4 ± 1.3 in current smokers, 5.2 ± 1.4 in former smokers and 5.1 ± 1.4 in never smokers (p = 0.011). The simple erosion narrowing score was higher in current smokers and former smokers than in never smokers (M 14.0, R Q 6.0-21.0; M 15.0, R Q 7.0-24.0; M 10.0, R Q 5.0-17.0; p = 0.006). Current smokers had higher rheumatoid factor titer (M 160.0, R Q 80.0-341.0) than former smokers (M 146.8, R Q 6.03-255.5) and never smokers (M 15.0, R Q 9.0-80.0) (p = 0.004). The variable independently associated with tobacco exposure was simple erosion narrowing score (OR = 1.03, 95 % CI 1.00-1.05; p = 0.012). In patients with undifferentiated arthritis, an association between smoking status and parameters of activity or radiographic damage was not observed. Neither was tobacco exposure related to the presence of extraarticular manifestations or to the degree of disability in any of the two groups of patients. No relation was found between disease activity and severity, and number of packs smoked per year. Tobacco.

Frecuencia de mortalidad en pacientes con artritis reumatoidea en un centro de reumatología de Argentina / Mortality rate in patients with rheumatoid arthritis in a rheumatology center of Argentina

La Artritis Reumatoidea (AR) es una enfermedad inflamatoria crónica que se asocia a disminución de la capacidad funcional, de la calidad de vida y aumento de la mortalidad. El objetivo de este estudio fue evaluar la mortalidad en una cohorte de pacientes con AR, y la influencia de factores sociodemográficos, clínicos y de laboratorio. Pacientes y métodos: Se analizó una cohorte de pacientes con diagnóstico de AR, (criterios ACR’ 87), evaluados entre los años 2004 y 2010. Se recolectaron datos sociodemográficos, características de la enfermedad, clínicas, analíticas, tratamientos recibidos y comorbilidades. Radiografías de manos y pies fueron leídas por medio del índice de Sharp van der Heijde por 3 observadores independientes ciegos (CCI ≥0,8). En caso de discontinuación del seguimiento, se realizó contacto telefónico. Se identificaron los pacientes fallecidos durante el período estudiado y se determinó la causa de muerte. Análisis estadístico: Estadística descriptiva, para la comparación de datos categóricos se utilizó test de Chi2 o test exacto de Fisher y para las variables continuas test t de Student o Mann Whitney según la distribución de la muestra. Los factores asociados a mortalidad se analizaron por regresión logística múltiple. Se consideró significativa una p <0,05. Resultados: Se evaluaron 307 pacientes, de los cuales 45 perdieron seguimiento y 262 pudieron ser reevaluados a los 5 años de seguimiento. De los 262 pacientes, 86,3% eran de sexo femenino, la edad mediana fue de 58 años (RIC 50-67), la edad mediana al inicio de la AR fue de 40 años (RIC 31-50) con un tiempo mediano de evolución de 15 años (RIC 10-21). 17 pacientes (6,5%) fallecieron. En el análisis univariado, mayor edad, menor escolaridad, presencia de comorbilidades gastrointestinales y uso de tratamiento biológico, estuvieron significativamente asociados con mayor mortalidad...

Rheumatoid arthritis (RA) is a chronic inflammatory disease that isassociated with decreased functional capacity, quality of life andincreased mortality. The aim of this study was to assess mortality ina cohort of patients with RA, and the influence of sociodemographic,clinical and laboratory factors.Patients and methods: A cohort of patients diagnosed withRA was evaluated (ACR' 87 criteria) between 2004 and 2010.Sociodemographic data, disease characteristics, clinical, laboratory,treatment received and comorbidities were collected. Radiographsof hands and feet were read by the Sharp van der HeijdeScore by 3 independent observers (ICC ≥0.8) blinded for diseasecharacteristics. If discontinuation of follow-up was present,telephone contact was made. Deceased patients were identifiedduring the study period and the cause of death was determined.Statistical analysis: Chi2 test or Fisher exact test were used forcategorical variables and Student t test or Mann Whitney forcontinues variables. Factors associated with mortality wereanalyzed by multiple logistic regression. P value <0.05 wasconsidered significative.Results: 307 patients were evaluated, of whom 45 were lost tofollow-up and 262 were reassessed after 5 years of follow-up. Of the262 patients, 86.3% were female, median age was 58 years (IQR 50-67), the median age at onset of RA was 40 years (IQR 31-50) with amedian disease duration of 15 years (IQR 10-21). Seventeen patients(6.5%) died. In univariate analysis, older age, lower education, presenceof gastrointestinal comorbidities and use of biological treatmentwere significantly associated with higher mortality. In multiple logisticregression analysis, worse educational level and use of biologicaltreatment were significantly associated with mortality...

4G/5G plasminogen activator inhibitor-1 and -308 A/G tumor necrosis factor-α promoter gene polymorphisms in Argentinean lupus patients: focus on lupus nephritis.

We investigated the relationship between the 4G/5G plasminogen activator inhibitor (PAI-1) and -308 A/G tumor necrosis factor-α (TNF-α) polymorphisms and the clinical and biochemical features of systemic lupus erythematosus (SLE) in an Argentinean patient cohort. A total of 402 patients were studied, including 179 SLE patients and 223 healthy individuals. PCR-RLFP was used to determine the genotypes of the 4G/5G PAI-1 and -308 A/G TNF-α polymorphisms. SLE patients with lupus nephritis (LN) (n = 86) were compared with patients without LN (n = 93). Additionally, LN patients were divided into proliferative LN and non-proliferative LN groups according to the results of the renal biopsies. No significant differences were noted in the genotype distributions or allele frequencies of these TNF-α and PAI-1 polymorphisms between SLE patients and controls. There were higher numbers of criteria for SLE, more lupus flares and higher damage scores in LN patients, but there were similar frequencies of anti-phospholipid antibody (APA) positivity and anti-phospholipid syndrome. No significant difference was noted for any studied variable between the proliferative LN and non-proliferative LN groups except for the presence of APA. We found no significant differences in the TNF-α and PAI-1 genotype distributions or allele frequencies between groups. We found that the -308 A/G TNF-α and 4G/5G PAI-1 polymorphisms are not associated with susceptibility to SLE in an Argentinean population. We also did not find any association between the presence of any specific allele or genotype and the development of LN in SLE patients. Finally, no association was noted between either of the two polymorphisms and the severity of renal disease.

Quality of life of patients with rheumatoid arthritis in Argentina: reliability, validity, and sensitivity to change of a Spanish version of the Rheumatoid Arthritis Quality of Life questionnaire.

The Rheumatoid Arthritis Quality of Life (RAQoL) questionnaire is the first needs-based instrument specifically designed to measure quality of life (QoL) of patients with rheumatoid arthritis (RA). The aims of our study were to develop an Argentinean version of the RAQoL and to determine its reproducibility, validity, and sensitivity to change in patients with RA. Translation process was performed according to internationally accepted methodology. Internal consistency and test-retest reliability were calculated. Criterion and construct validity were assessed by comparing the RAQoL with parameters of disease activity, the Health Assessment Questionnaire (HAQ), and the Medical Outcomes Study 36-item health survey (SF-36) questionnaire. Sensitivity to change was measured at 6-12 months using standardized response mean (SRM). The minimal important change was defined as a change of 1 or 1.96 times the standard error of measurement. A total of 97 patients with RA were included. Cronbach's α was 0.93, and test-retest reliability was 0.95. The RAQoL showed moderate to strong correlation with parameters of disease activity, the HAQ, and the SF-36. Functional status was the main determinant of patients' level of QoL. The SRM of the RAQoL was 0.24. Agreement between 20 % improvement in RAQoL and ACR20 response was moderate. Minimal important change was 2.2 (1 SEM) or 4.3 (1.96 SEM). The Argentinean version of the RAQoL is the first Spanish translation of this questionnaire. Our findings show it to be valid, reliable, and sensitive to changes in RA clinical status.

Seguridad de abatacept en pacientes con artritis reumatoidea / Safety of abatacept in patients with rheumatoid arthritis

Abatacept (ABA) es una proteína de fusión que inhibe la señal coestimulatoria del linfocito T y está indicado en pacientes con artritis reumatoidea (AR) y artritis crónica juvenil moderada a severa sin respuesta a metotrexato (MTX). ABA ha demostrado su eficacia y seguridad en numerosos estudios controlados, doble ciego, randomizados en poblaciones seleccionadas. La incidencia de eventos adversos en estos estudios oscila entre 80 y 400 por 100 pacientes año. El objetivo del presente estudio fue evaluar la seguridad de ABA en pacientes con AR no seleccionados de la vida real. Material y métodos: Se incluyeron en forma consecutiva todos los pacientes con AR (criterios ACR'87) de 4 centros de reumatología que hubieran recibido al menos 1 dosis de ABA. Se consignaron datos socio-demográficos, características clínicas de la enfermedad, número de infusiones, dosis, y medicación concomitante. Se evaluaron todos los eventos adversos y se determinó la severidad y causalidad. Se consideraron las causas de suspensión del tratamiento. Análisis estadístico: Se evaluó la incidencia de eventos adversos/100 pacientes año de tratamiento, las variables categóricas fueron comparadas por Chi cuadrado y las continuas por test de Student o ANOVA...

Abatacept (ABA) is a fusion protein that inhibits the T cell costimulatorysignal and is indicated in patients with moderate to severe RheumatoidArthritis (RA) and Juvenil Idiopathic Arthritis, not responding to methotrexate. ABA has demonstrated eficacy and security in severalcontrolled, double-blind, randomized studies in selected populations.The objective of the present study was to evaluate security of ABA in patients with RA in the real life. Material and Methods: Consecutive patients with RA (ACR´87 classification) from 4 rheumatology centers that received at least one infusion of ABA were included. Socio-demographic data, disease characteristics, number of infusions, dosis, and concomitant medicationswere registered. All Adverse Events (AE) were evaluated and severityand causality were determined. Causes of treatment discontinuationwas also considered.Statistical analysis: Incidence of AE per 100 patient-years was evaluated, categorical variables were compared by Chi2 and continuous variables by Student T-test or ANOVA. Results: 184 patients were included, 155 (84.2%) were female, median age was 56 years (IQR 48-64) and median duration of disease was 13 years (IQR 8-18). 94.7% of the patients were rheumatoidfactor-positive and 82% had erosive disease. 90% were treatedwith concomitant DMARDs, methotrexate being the most frequent(76.5%). In 67% of the patients ABA was the first biologic agent used, and 23% had previously received at least one anti-TNF. Median duration of treatment with ABA was 24 months (IQR 11-34) and median number of infusions was 23 (IQR 10-34). Incidence of all AE was 46.18 per 100 patient-years, being the more frequents: Infections (27.3 per 100 patient-years), and infusion reactions (8.6 per100 patient-years)...

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.