Caracterización epidemiológica de la artritis idiopática juvenil y refractariedad a dmard en una institución en Bogotá

La artritis idiopática juvenil (AIJ) es la enfermedad reumatológica crónica más común de la infancia con repercusiones importantes en la calidad de vida del paciente y su familia; las alteraciones físicas presentadas pueden ocasionar ausentismo escolar. Los tratamientos de uso crónico utilizados hacen que la adherencia al mismo en la población infantil y adolescente sea todo un reto. A esto se adiciona la refractariedad a DMARDs (Disease – Modifying – Antirheumatic – Drugs) que conlleva al inicio de terapia biológica y a cambios en el pronóstico de la enfermedad. Materiales y métodos: Estudio observacional retrospectivo mediante la revisión de las historias clínicas de pacientes con diagnóstico de artritis idiopática juvenil que consultaron a la Fundación Cardioinfantil desde enero del 2008 a septiembre de 2015. Se obtuvieron datos como edad, sexo, edad de diagnóstico, manejo actual, remisión, seguimiento, tratamiento, cambios realizados en el mismo y refractariedad a DMARD. Resultados: De 108 registros clínicos evaluados, 90 cumplieron los criterios de elegibilidad. Se diagnosticó con mayor frecuencia en el sexo femenino con un 57.8%, media de edad de 7.88 años. El subtipo poliarticular con Factor Reumatoideo negativo se presentó con una frecuencia con 31,1 %. El tiempo transcurrido entre el inicio de la sintomatología en meses, previo a realizar el diagnóstico, osciló entre 1 y 60 meses con una media de 10,6 meses. Se usaron con mayor frecuencia: AINES (61,1%), metotrexate (47,8%) y corticoides (42,2%). De los 90 pacientes, solo un 11.1% de la población presentó complicaciones, siendo la más frecuente la obesidad en un 3,3 % y la menos frecuente la uveítis con un 1,1%. Discusión: Es importante el entendimiento de la Artritis idiopática juvenil como una entidad de carácter sistémica, lo cual hace necesario el conocimiento de la epidemiología para establecer estrategias de manejo y seguimiento adecuadas. El género femenino continúa siendo afectado en mayor porcentaje. Se observaron leves cambios respecto al subtipo de mayor frecuencia comparado con estudios previos. Se necesitan más estudios de caracterización epidemiológica en la población Colombiana para realización de políticas de salud pública

Putative antinociceptive action of nitric oxide in the caudal part of the spinal trigeminal nucleus during chronic carrageenan-induced arthritis in the rat temporomandibular joint

In order to investigate a putative role for nitric oxide (NO) in the central nociceptive processing following carrageenan-induced arthritis in the rat temporomandibular joint (TMJ), we analyzed the immunoreactivity, gene expression and activity of nitric oxide synthases (NOS) in the caudal part of the spinal trigeminal nucleus (Sp5C) during the acute (24 h), chronic (15 days) and chronic-active (14 days-24 h) arthritis. In addition, evaluation of head-withdrawal threshold was carried out in all phases of arthritis under chronic inhibition of nNOS with the selective inhibitor 7-nitroindazole (7-NI). Neurons with nNOS-like immunoreactivity (nNOS-LI) were concentrated mainly in the lamina II of the Sp5C, showing no significant statistical difference during arthritis. Only a discrete percentage of nNOS-LI neurons expressed Fos immunoreactivity. The mRNA expression for both nNOS and endothelial nitric oxide synthases (eNOS) presented no noticeable differences among the groups. No expression of inducible nitric oxide synthase (iNOS) was detected in the Sp5C by either immunohistochemistry or reverse-transcription polymerase chain reaction (RTPCR). Ca(2+)-dependent NOS activity in the ipsilateral Sp5C was significantly higher (108.3 +/- 49.2%; P<0.01) in animals during the chronic arthritis. Interestingly, this increased activity was completely abolished 24 h later, in the chronic-active arthritis. Finally, head-withdrawal threshold decreased significantly in the chronic arthritis in animals under 7-NI chronic inhibition. In conclusion, nNOS immunoreactivity and mRNA expression are stable in the Sp5C during TMJ arthritis evolution, but its activity significantly increases in the chronic-phases supporting an antinociceptive role of the nNOS as evidenced by pain threshold experiment. (C) 2009 Elsevier B.V. All rights reserved.

Adenosine deaminase activity as a biochemical marker of inflammatory response in goats infected by caprine arthritis-encephalitis virus

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Yersinia enterocolitica O : 3 isolated from patients with or without reactive arthritis induces polyclonal activation of B cells and autoantibody production in vivo

The mechanisms by which arthritis-provoking pathogens such as Yersinia enterocolitica interact with the human immune system to produce inflammatory synovitis are not well known. One of the immunomodulating mechanisms used against these pathogens is the polyclonal activation of lymphocytes. In this study, we investigated the extent of the B-lymphocyte activation induced in mice by a strain of Y. enterocolitica O:3 (FCF 526) isolated from a patient with arthritis, and compared it with two other strains, a virulent one (FCF 397[+]) isolated from a patient without arthritis and its plasmidless isogenic pair (FCF397[-]). Also we investigated the production of autoantibodies in mice infected with these different strains. SPF Swiss mice were infected intravenously with a suspension of Y. enterocolitica . Spleen cells were taken on days 7, 14, 21 and 28 after infection and the number of cells secreting nonspecific and specific antibodies of IgG 1 , IgG 2a , IgG 2b , IgG 3 , IgM and IgA isotypes were determined by the ELISPOT technique. The presence of autoantibodies in mouse serum was investigated by the dot-blot assay. The pattern of infection of the three bacterial strains were almost the same. We observed a general increase in the number of nonspecific Ig-secreting cells with all three strains, and the greatest increases observed were in the IgG 2a and IgG 3 isotypes. Only a small fraction of the immunoglobulins detected were antibacterial, suggesting that the rest resulted from polyclonal B cell activation. The strain isolated from the patient with arthritis (FCF526) induced the greatest production of autoantibodies, coinciding with the period in which the greatest activation of nonspecific B lymphocytes was seen. There were no signs of arthritis or inflammation in the joints of the infected animals. Based on our results, we were unable to determine whether there is an association between the arthritogenic capability of Y. enterocolitica and polyclonal activation of B cells.

Remission status follow-up in children with juvenile idiopathic arthritis

Objective: To characterize articular and systemic inflammatory activity in juvenile idiopathic arthritis (JIA), identifying remission status with and without medication.Methods: A total of 165 JIA cases, followed for a mean period of 3.6 years, were reviewed in order to characterize episodes of inactivity and clinical remission on and off medication. The resulting data were analyzed by means of descriptive statistics, survival analysis, by comparison of Kaplan-Meier curves, log rank testing and binary logistic regression;analysis in order to identify predictive factors for remission or persistent activity.Results: One hundred and eight of the cases reviewed fulfilled the inclusion criteria: 57 patients (52.7%) exhibited a total of 71 episodes of inactivity, with a mean of 2.9 years per episode; 36 inactivity episodes (50.7%) resulted in clinical remission off medication, 35% of which were of the persistent oligoarticular subtype. The probability of clinical remission on medication over 2 years was 81, 82, 97 and 83% for cases of persistent oligoarticular, extended oligoarticular, polyarticular and systemicJIA, respectively. The probability of clinical remission off medication 5 years after onset of remission was 40 and 67% for patients with persistent oligoarticular and systemic JIA, respectively. Persistent disease activity was significantly associated with the use of an anti-rheumatic drug combination. Age at JIA onset was the only factor that predicted clinical remission (p = 0.002).Conclusions: In this cohort, the probability of JIA progressing to clinical remission was greater for the persistent oligoarticular and systemic subtypes, when compared with polyarticular cases.

Progression of articular and extraarticular damage in oligoarticular juvenile idiopathic arthritis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

A new short and simple health-related quality of life measurement for paediatric rheumatic diseases: initial validation in juvenile idiopathic arthritis

Objective. To develop and validate a new short and simple measure of health-related quality of life (HRQL) in children with juvenile idiopathic arthritis (JIA).Methods. The Paediatric Rheumatology Quality of Life Scale (PRQL) is a 10-item questionnaire that explores HRQL in two domains: physical health (PhH) and psychosocial health (PsH). Validation of the parent proxy report and child self-report versions of the instrument was accomplished by evaluating 472 JIA patients and similar to 800 healthy children. Validation analyses included assessment of feasibility, face and content validity; construct and discriminative ability; internal structure and consistency; test-retest reliability; responsiveness to clinical change; and minimal clinically important difference.Results. The PRQL was found to be feasible and to possess both face and content validity. The PRQL score correlated in the predicted range with most of the other JIA outcome measures, thereby demonstrating good construct validity, and discriminated well between different levels of disease severity. Assessment of internal structure (factor analysis) revealed that the PhH and PsH subscales identify two unambiguously separated domains. The internal consistency (Cronbach's alpha) was 0.86. The intraclass correlation coefficient for test-retest reliability was 0.91. The PRQL revealed fair responsiveness, with a standardized response mean of 0.67 in improved patients. Overall, the PRQL appeared to be more able to capture physical HRQL than psychosocial HRQL.Conclusion. The PRQL was found to possess good measurement properties and is, therefore, a valid instrument for the assessment of HRQL in children with JIA. This tool is primarily proposed for use in standard clinical care.

Long-Term Safety and Efficacy of Abatacept in Children With Juvenile Idiopathic Arthritis

Objective. We previously documented that abatacept was effective and safe in patients with juvenile idiopathic arthritis (JIA) who had not previously achieved a satisfactory clinical response with disease-modifying antirheumatic drugs or tumor necrosis factor blockade. Here, we report results from the long-term extension (LTE) phase of that study.Methods. This report describes the long-term, open-label extension phase of a double-blind, randomized, controlled withdrawal trial in 190 patients with JIA ages 6-17 years. Children were treated with 10 mg/kg abatacept administered intravenously every 4 weeks, with or without methotrexate. Efficacy results were based on data derived from the 153 patients who entered the open-label LTE phase and reflect >= 21 months (589 days) of treatment. Safety results include all available open-label data as of May 7, 2008.Results. of the 190 enrolled patients, 153 entered the LTE. By day 589, 90%, 88%, 75%, 57%, and 39% of patients treated with abatacept during the double-blind and LTE phases achieved responses according to the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30), Pedi 50, Pedi 70, Pedi 90, and Pedi 100 criteria for improvement, respectively. Similar response rates were observed by day 589 among patients previously treated with placebo. Among patients who had not achieved an ACR Pedi 30 response at the end of the open-label lead-in phase and who proceeded directly into the LTE, 73%, 64%, 46%, 18%, and 5% achieved ACR Pedi 30, Pedi 50, Pedi 70, Pedi 90, and Pedi 100 responses, respectively, by day 589 of the LTE. No cases of tuberculosis and no malignancies were reported during the LTE. Pneumonia developed in 3 patients, and multiple sclerosis developed in 1 patient.Conclusion. Abatacept provided clinically significant and durable efficacy in patients with JIA, including those who did not initially achieve an ACR Pedi 30 response during the initial 4-month open-label lead-in phase.

Putative antinociceptive action of nitric oxide in the caudal part of the spinal trigeminal nucleus during chronic carrageenan-induced arthritis in the rat temporomandibular joint

In order to investigate a putative role for nitric oxide (NO) in the central nociceptive processing following carrageenan-induced arthritis in the rat temporomandibular joint (TMJ), we analyzed the immunoreactivity, gene expression and activity of nitric oxide synthases (NOS) in the caudal part of the spinal trigeminal nucleus (Sp5C) during the acute (24 h), chronic (15 days) and chronic-active (14 days-24 h) arthritis. In addition, evaluation of head-withdrawal threshold was carried out in all phases of arthritis under chronic inhibition of nNOS with the selective inhibitor 7-nitroindazole (7-NI). Neurons with nNOS-like immunoreactivity (nNOS-LI) were concentrated mainly in the lamina II of the Sp5C, showing no significant statistical difference during arthritis. Only a discrete percentage of nNOS-LI neurons expressed Fos immunoreactivity. The mRNA expression for both nNOS and endothelial nitric oxide synthases (eNOS) presented no noticeable differences among the groups. No expression of inducible nitric oxide synthase (iNOS) was detected in the Sp5C by either immunohistochemistry or reverse-transcription polymerase chain reaction (RTPCR). Ca(2+)-dependent NOS activity in the ipsilateral Sp5C was significantly higher (108.3 +/- 49.2%; P<0.01) in animals during the chronic arthritis. Interestingly, this increased activity was completely abolished 24 h later, in the chronic-active arthritis. Finally, head-withdrawal threshold decreased significantly in the chronic arthritis in animals under 7-NI chronic inhibition. In conclusion, nNOS immunoreactivity and mRNA expression are stable in the Sp5C during TMJ arthritis evolution, but its activity significantly increases in the chronic-phases supporting an antinociceptive role of the nNOS as evidenced by pain threshold experiment. (C) 2009 Elsevier B.V. All rights reserved.

Phenotypic alterations of neuropeptide Y and calcitonin gene-related peptide-containing neurons innervating the rat temporomandibular joint during carrageenan-induced arthritis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

PCR associated with agar gel immunodiffusion assay improve caprine arthritis-encephalitis (CAEV) control

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Laser treatment of experimentally induced chronic arthritis

In this work, we investigated the effects of He-Ne laser irradiation on the inflammatory process induced in the articular cartilage of the right knee of guinea pigs. Through electron microscopy analysis it was possible to identify the induced arthritis in the articular cartilage and its modification after the laser treatment. The laser radiation promoted a reduction in the proliferation of the inflammatory cells in the damaged tissue and also induced the formation of cartilage bridges that tied the destroyed parts favoring the formation of a repaired tissue in the injured cartilage. (C) 2000 Elsevier B.V. B.V. All rights reserved.