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.

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.

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.

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.

[Anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis: relation with clinical features, cytokines and HLA-DRB1]. / Anticuerpos anti-CCP en artritis reumatoidea: relación con características clínicas, citocinas Th1/Th2 y HLA-DRB1.

The specificity and sensitivity of anti-cyclic citrullinated peptide antibodies (anti-CCP) was examined in Latin-American patients with rheumatoid arthritis (RA). The variables considered included: 1) relation with the activity of disease, 2) extra-articular manifestations (EAM), 3) synthesis of cytokines (IL-4, IL-10, IL-12, TNF-alpha, and IFN-gamma) and IgM and IgA rheumatoid factor (RF), and 4) the association with HLA-DRB1 polymorphism. Seventy-nine RA patients were assessed (69 with established RA, and 10 with recent-onset RA not receiving any treatment), 56 with ankylosing spondylitis (AS), 25 with systemic lupus erythematosus (SLE), 50 with primary Sjögren's syndrome (pSS), and 10 healthy individuals. Of the 69 patients with established RA, 36 were reexamined 2 years later. The activity of the RA was measured by criteria adopted by the American College of Rheumatology. Anti-CCP2, RF and cytokines levels were determined by ELISA. HLA genotypes were established by first, PCR sequence amplification using sequence-specific primers and then, complete sequencing of the product. Anti-CCP antibodies were observed in 96% of patients with RA during the first evaluation and in 86% at the second evaluation (p = 0.12). No significant change in antibody titre was observed between the two evaluations (131 +/- 58.7 and 130.6 +/- 67.1 IU, respectively). The overall sensitivity and specificity was 94% and 92%, respectively; however, at titres > 60 IU, the values were 84% and 95%, respectively. The anti-CCP likelihood ratio positive test was 12 and the likelihood ratio negative test was 0.06. The positive predictive value was 87%, and the negative predictive value was 96%. Anti-CCP antibodies were observed in 12% of SLE and pSS patients, in 2% of AS patients, and in 10% of healthy controls. In RA patients, these antibodies were not associated with the activity of disease, EAM or HLA-DRB1 alleles; no significant correlation was observed between antibody titre and cytokines level. Although anti-CCP antibodies have potential as a diagnostic tool for RA, they are not useful for monitoring clinical activity or predicting the clinical course of disease. Antibody synthesis is HLA-DRB1 independent and not correlated with Th1/Th2 cytokines.

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.

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.

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.

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.

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.

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.

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.

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.

Polyarteritis nodosa revisited.

Polyarteritis nodosa (PAN), the prototype of systemic vasculitis, is a rare condition characterized by necrotizing inflammation of medium-sized or small arteries without glomerulonephritis or vasculitis in arterioles, capillaries, or venules. Signs and symptoms of this disease are primarily attributable to diffuse vascular inflammation and ischemia of affected organs. Virtually any organ with the exception of the lungs may be affected, with peripheral neuropathy and symptoms from osteoarticular, renal artery, and gastrointestinal tract involvement being the most frequent clinical manifestations. A clear distinction between limited versus systemic disease and idiopathic versus hepatitis B related PAN should be done because there are differences in the implicated pathogenetic mechanisms, their treatment, and prognosis. Currently, corticosteroids plus cyclophosphamide is the standard of care for idiopathic PAN, in particular for patients with adverse prognostic factors (more severe disease), in whom this combination prolonged survival. In contrast for hepatitis B related PAN treatment consists of schemes that include plasmapheresis and antiviral agents.

Audiovestibular disorders in patients with ankylosing spondylitis.

OBJECTIVE: Audiovestibular disorders have been described in several autoimmune diseases but have not been studied in patients with ankylosing spondylitis (AS). The aim of this study was to evaluate the audiovestibular function in patients with AS. METHODS: We prospectively evaluated 22 consecutive patients with AS. Clinical, radiologic, and immunogenetic features were analyzed. All patients underwent a complete ear, nose, and throat physical examination and audiologic evaluation that included pure-tone audiometry thresholds at octave frequencies of 250 to 8000 Hz, impedance audiometry (tympanogram, static compliance, acoustic reflexes, and reflex decay), and speech audiometry. Thirty-one healthy volunteers and 26 patients with rheumatoid arthritis (RA) were included as controls. RESULTS: Patients with AS had a median age of 45.5 years (interquartile range [IQR] 38-54) and a median disease duration of 20 years (IQR 12.5-26.2). Otosclerosis was observed in 2 patients with AS (9.1%), 3 patients with RA (11.5%), but not in any healthy controls (P = not significant). Sensorineural hearing loss (SNHL) was observed in 13 patients with AS (59%), 17 patients with RA (65.4%), and 13 healthy controls (41.9%) without statistically significant differences. Because age can influence audiometric results, patients and controls were divided into 4 age groups. A higher frequency of SNHL was observed in patients with AS from 45 to 59 years compared with healthy controls and patients with RA (87% versus 20%, P = 0.03, versus 70%, P = not significant, respectively). CONCLUSION: Middle-aged patients with AS had a significantly higher frequency of SNHL compared with controls. SNHL should be considered as a possible complication of AS as well as of RA and other autoimmune diseases. Possible toxic effect of nonsteroidal antiinflammatory drugs should also be considered in such patients.

Validation and crosscultural adaptation of an argentine spanish version of the health assessment questionnaire disability index.

BACKGROUND: The Health Assessment Questionnaire (HAQ) is one of the most frequently used instruments to assess functional capacity in activities of daily living. OBJECTIVE: The objective of our study was to determine the reproducibility and validity of an Argentinean version of the HAQ disability index (HAQ-DI) in patients with rheumatoid arthritis (RA). METHODS: Consecutive adult patients with RA from 3 different provinces in Argentina were included. The original English version of the HAQ-DI was translated and adapted into Spanish by 3 rheumatologists and the final version back translated into English by a bilingual person. The reproducibility of the questionnaire was assessed in 30 patients who came for a second visit 3 to 5 days later. The cross-sectional construct validity was assessed by comparing the HAQ with classic parameters of disease activity (number of swollen and tender joints, patient and physician visual analog scale for pain and activity as well as functional class, erythrocyte sedimentation rate, and C-reactive protein. RESULTS: Two hundred patients with RA were included. The reproducibility was r = 0.97 (P = 1 x 10-5); intraitem correlation analysis did not show any redundancy. Correlation between HAQ-A and parameters of disease activity were all significant. A stepwise multiple regression analysis showed that the main variables associated with HAQ-A scores were visual analog scale for pain and duration of morning stiffness. A weak although significant negative correlation was found between the HAQ-A and economic level (r = -0.21, P = 0.03). The median time to complete the questionnaire was 5 minutes and there were no problems with any questions. CONCLUSION: This version of the HAQ-DI would allow for more availability so that Spanish-speaking countries can select the version most suitable to their sociocultural environment.

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.

Effects of functional electrostimulation on pain, muscular strength, and functional capacity in patients with osteoarthritis of the knee.

BACKGROUND: Osteoarthritis (OA) of the knee is a common cause of chronic disability in patients with quadriceps muscle weakness. Beneficial effects have been proposed for functional electrostimulation (FES) and exercise at the muscle level. OBJECTIVES: The objective of the study was to begin to compare the effects of both therapeutic modalities on quadriceps muscle strength, pain, and functional capacity in patients with OA of the knee and to prove whether the combination of these modalities provides greater benefits than the use of each therapeutic modality alone. METHODS: This pilot study included 37 patients with OA of the knee who were assessed at baseline and at 8 weeks, accounting for the following variables: body mass index, knee pain (measured using a VAS), WOMAC, quadriceps strength (measured using a dynamometer) and 6-minute walk test. Patients were randomized into 3 groups: (A) 8 patients who received FES 3 times per week; (B) 10 patients recruited into a twice-a-week physical training program; and (C) 8 patients under combined therapy; 29.7% of patients were lost to follow-up due to noncompliance with the treatment plan, leaving a total of 26 patients at 8 weeks. RESULTS: Pain and WOMAC improved in all 3 groups; strength improved significantly in the exercise-only group; the FES + exercise combination improved strength significantly when compared with the individual therapeutic procedures. CONCLUSIONS: FES merits a larger placebo-controlled study as it may prove to be useful patients with OA of the knee; the combination with exercise was helpful in improving muscle strength. This technique may be considered in patients who are unable to carry out physical activity due to health problems or in those who are not interested in physical activity.