Equivalência métrica do Disease Activity Score (DAS 28) e Juvenile Arthritis Disease Activity Score (JADAS) na artrite idiopática juvenil

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Comparação entre o Disease Activity Score-28 e o Juvenile Arthritis Disease Activity Score na artrite idiopática juvenil

Introduction: the assessment of the activity of rheumatoid arthritis and juvenile idiopathic arthritis is made by means of different tools, respectively DAS-28 and JADAS.Objective: To compare DAS-28 and JADAS with scores of 71, 27 and 10 joint counts in juvenile idiopathic arthritis.Method: A secondary analysis of a phase III placebo-controlled trial, testing safety and efficacy of abatacept was conducted in 8 patients with 178 assessment visits. Joint count scores for active and limited joints, physician's and parents'global assessment by 0-10 cm Visual Analog Scale, and erythrocyte sedimentation rate normalized to 0-10 scale, in all visits. The comparison among the activity indices in different observations was made through Anova or adjusted gamma model. The paired observations between DAS-28 and JADAS 71, 27 and 10, respectively, were analyzed by linear regression.Results: There were significant differences among individual measures, except for ESR, in the first four months of biological treatment, when five of the eight patients reached ACR-Pedi 30, with improvement. The indices of DAS-28, JADAS 71, 27 and 10 also showed significant difference during follow-up. Linear regression adjusted model between DAS-28 and JADAS resulted in mathematical formulas for conversion: [DAS-28 = 0.0709 (JADAS 71) + 1.267] (R-2 = 0.49); [DAS-28 = 0.084 (JADAS 27) + 1.7404] (R-2 = 0.47) and [DAS-28 = 0.1129 (JADAS-10) + 1.5748] (R-2 = 0.50).Conclusion: The conversion of scores of DAS-28 and JADAS 71, 27 and 10 for this mathematical model would allow equivalent application of both in adolescents with arthritis. (C) 2014 Elsevier Editora Ltda. All rights reserved.

Adaptação cultural e validação do JAMAR - Juvenile Arthritis Multidimensional Assessment Report para a artrite idiopática juvenil

Pós-graduação em Saúde Coletiva - FMB

Comparative analysis of synovial fluid and plasma proteomes in juvenile arthritis - Proteomic patterns of joint inflammation in early stage disease

Synovial fluid is a potential source of novel biomarkers for many arthritic disorders involving joint inflammation, including juvenile idiopathic arthritis. We first compared the distinctive protein ‘fingerprints’ of local inflammation in synovial fluid with systemic profiles within matched plasma samples. The synovial fluid proteome at the time of joint inflammation was then evaluated across clinical subgroups to identify early disease associated proteins. We measured the synovial fluid and plasma proteomes using the two-dimensional fluorescence difference gel electrophoresis approach. Image analysis software was used to highlight the expression levels of joint and subgroup associated proteins across the study cohort (n = 32). A defined subset of 30 proteins had statistically significant differences (p < 0.05) between sample types such that synovial fluid could be differentiated from plasma. Furthermore distinctive synovial proteome expression patterns segregate patient subgroups. Protein expression patterns localized in the chronically inflamed joint therefore have the potential to identify patients more likely to suffer disease which will spread from a single joint to multiple joints. The proteins identified could act as criteria to prevent disease extension by more aggressive therapeutic intervention directed at an earlier stage than is currently possible.

Circulating and synovial antibody profiling of juvenile arthritis patients by nucleic acid programmable protein arrays.

Introduction Juvenile idiopathic arthritis (JIA) is a heterogeneous disease characterized by chronic joint inflammation of unknown cause in children. JIA is an autoimmune disease and small numbers of auto-antibodies have been reported in JIA patients. The identification of antibody markers could improve the existing clinical management of patients. Methods A pilot study was performed on the application of a high-throughput platform, nucleic acid programmable protein arrays (NAPPA), to assess the levels of antibodies present in the systemic circulation and synovial joint of a small cohort of juvenile arthritis patients. Plasma and synovial fluid from ten JIA patients was screened for antibodies against 768 proteins on NAPPA. Results Quantitative reproducibility of NAPPA was demonstrated with >0.95 intra- and inter- array correlations. A strong correlation was also observed for the levels of antibodies between plasma and synovial fluid across the study cohort (r=0.96). Differences in the levels of 18 antibodies were revealed between sample types across all patients. Patients were segregated into two clinical subtypes with distinct antibody signatures by unsupervised hierarchical cluster analysis. Conclusions NAPPA provides a high-throughput quantitatively reproducible platform to screen for disease specific autoantibodies at the proteome level on a microscope slide. The strong correlation between the circulating antibody levels and those of the inflamed joint represents a novel finding and provides confidence to use plasma for discovery of autoantibodies in JIA, thus circumventing the challenges associated with joint aspiration. We expect that autoantibody profiling of JIA patients on NAPPA could yield antibody markers that can act as criteria to stratify patients, predict outcomes and understand disease etiology at the molecular level.

Uma análise clinimétrica dos índices articular extra-articular do Juvenile Arthritis Damage Index(JADI-A e JADI-E) na artrite isiopática juvenil

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

[Eye complications in chronic juvenile arthritis]

BACKGROUND: The relationship between uveitis anterior in childhood and juvenile chronic arthritis (JCA, respectively JRA) has been known since 1950. In a review, the clinical picture of uveitis anterior, its prevalence, pathogenesis, prognosis and current therapy of ocular complications are presented. In addition, we will report our results of a clinical study. PATIENTS AND METHODS: In a cross-sectional study, 64 patients with juvenile chronic arthritis (JCA) had an ophthalmological screening for eye complications either from the disease itself or from the treatment. RESULTS: In 16% of the patients, an iridocyclitis was found, in one case acute, in 9 cases chronic. The cases of chronic uveitis anterior showed in 43% a combination with the classic risk factors (ANA-positive, oligoarticular, female). At the beginning of uveitis, the patients had a mean age of 81 months, at the beginning of JCA disease a mean age of 37 months. Four of 10 patients (= 40%) had eye complications from uveitis (cataract, posterior synechiae, glaucoma). Complications from therapy were found in 27%, mostly cataract as a complication of systemic and topical steroid treatment. Eighteen % had a visual acuity of 0.4 or less. CONCLUSIONS: Because of the often asymptomatic progression of chronic uveitis anterior, the risk of severe undetected eye complications is high. Therefore, an intensive interdisciplinary cooperation between rheumatologists, pediatrics and ophthalmologists is required.

Determinants of discordance in patients' and physicians' rating of rheumatoid arthritis disease activity

Objective To assess the determinants of patients' (PTGL) and physicians' (MDGL) global assessment of rheumatoid arthritis (RA) activity and factors associated with discordance among them. Methods. A total of 7,028 patients in the Quantitative Standard Monitoring of Patients with RA study had PTGL and MDGL assessed at the same clinic visit on a 0-10-cm visual analog scale (VAS). Three patient groups were defined: concordant rating group (PTGL and MDGL within >= 2 cm), higher patient rating group (PTGL exceeding MDGL by > 2 cm), and lower patient rating group (PTGL less than MDGL by > 2 cm). Multivariable regression analysis was used to identify determinants of PTGL and MDGL and their discordance. Results. The mean +/- SD VAS scores for PTGL and MDGL were 4.01 +/- 2.70 and 2.91 +/- 2.37, respectively. Pain was overwhelmingly the single most important determinant of PTGL, followed by fatigue. In contrast, MDGL was most influenced by swollen joint count (SJC), followed by erythrocyte sedimentation rate (ESR) and tender joint count (TJC). A total of 4,454 (63.4%), 2,106 (30%), and 468 (6.6%) patients were in the concordant, higher, and lower patient rating groups, respectively. Odds of higher patient rating increased with higher pain, fatigue, psychological distress, age, and morning stiffness, and decreased with higher SJC, TJC, and ESR. Lower patient rating odds increased with higher SJC, TJC, and ESR, and decreased with lower fatigue levels. Conclusion. Nearly 36% of patients had discordance in RA activity assessment from their physicians. Sensitivity to the "disease experience" of patients, particularly pain and fatigue, is warranted for effective care of RA.

Medicines optimisation for young people with juvenile arthritis and other long-term conditions:system-level barriers to engagement

To explore the views of pharmacy and rheumatology stakeholders about system-related barriers to medicines optimisation activities with young people with long-term conditions. A three-phase consensus-building study comprising (1) focus groups with community and hospital pharmacists; (2) semi-structured telephone interviews with lay and professional adolescent rheumatology stakeholders and pharmacy policymakers, and (3) multidisciplinary discussion groups with community and hospital pharmacists and rheumatology staff. Qualitative verbatim transcripts from phases 1 and 2 were subjected to framework analysis. Themes from phase 1 underpinned a briefing for phase 2 interviewees. Themes from phases 1 and 2 generated elements of good pharmacy practice and current/future pharmacy roles for ranking in phase 3. Results from phase 3 prioritisation and ranking exercises were captured on self-completion data collection forms, entered into an Excel spreadsheet and subjected to descriptive statistical analysis. Institutional ethical approval was given by Aston University Health and Life Sciences Research Ethics Committee. Four focus groups were conducted with 18 pharmacists across England, Scotland and Wales (7 hospital, 10 community and 1 community/public health). Fifteen stakeholders took part in telephone interviews (3 pharmacist commissioners; 2 pharmacist policymakers; 2 pharmacy staff members (1 community and 1 hospital); 4 rheumatologists; 1 specialist nurse, and 3 lay juvenile arthritis advocates). Twenty-five participants took part in three discussion groups in adolescent rheumatology centres across England and Scotland (9 community pharmacists; 4 hospital pharmacists; 6 rheumatologists; 5 specialist nurses, and 1 physiotherapist). In all phases of the study, system-level issues were acknowledged as barriers to more engagement with young people and families. Community pharmacists in the focus groups reported that opportunities for engaging with young people were low if parents collected prescriptions alone, which was agreed by other stakeholders. Moreover, institutional/company prescription collection policies – an activity largely disallowed for a young person under 16 without an accompanying parent - were identified by hospital and community pharmacists as barriers to open discussion and engagement. Few community pharmacists reported using Medicines Use Review (England/Wales) or Chronic Medication Service (Scotland) as a medicines optimisation activity with young people; many were unsure about consent procedures. Despite these limitations, rheumatology stakeholders ranked highly the potential of pharmacists empowering young people with general health care skills, such as repeat prescription ordering. The pharmacy profession lacks vision for its role in the care of young people with long-term conditions. Pharmacists and rheumatology stakeholders identified system-level barriers to more engagement with young people who take medicines regularly. We acknowledge that the modest number of participants may have had a specific interest and thus bias for the topic, but this underscores their frank admission of the challenges. Professional guidance and policy, practice frameworks and institutional/company policies must promote flexibility for pharmacy staff to recognise and empower young people who are able to give consent and take responsibility for medicines activities. This will increase mutual confidence and trust, and foster pharmacy’s role in teaching general health care skills. In this way, pharmacists will be able to build long-term relationships with young people and families.

The intestinal microbiome in human disease and how it relates to arthritis and spondyloarthritis

Humans and microbes have developed a symbiotic relationship over time, and alterations in this symbiotic relationship have been linked to several immune mediated diseases such as inflammatory bowel disease, type 1 diabetes and spondyloarthropathies. Improvements in sequencing technologies, coupled with a renaissance in 16S rRNA gene based community profiling, have enabled the characterization of microbiomes throughout the body including the gut. Improved characterization and understanding of the human gut microbiome means the gut flora is progressively being explored as a target for novel therapies including probiotics and faecal microbiota transplants. These innovative therapies are increasingly used for patients with debilitating conditions where conventional treatments have failed. This review discusses the current understanding of the interplay between host genetics and the gut microbiome in the pathogenesis of spondyloarthropathies, and how this may relate to potential therapies for these conditions.

Progression of articular and extraarticular damage in oligoarticular juvenile idiopathic arthritis

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

Exercise training in juvenile dermatomyositis

Objective. To investigate the effects of a supervised exercise training program on health parameters, physical capacity, and health-related quality of life in patients with mild and chronic juvenile dermatomyositis (DM). Methods. This was a prospective longitudinal study following 10 children with mild and chronic juvenile DM (disease duration >1 year). The exercise program consisted of twice-a-week aerobic and resistance training. At baseline and after the 12-week intervention, we assessed muscle strength and function, aerobic conditioning, body composition, juvenile DM scores, and health-related quality of life. Results. Child self-report and parent proxy-report Pediatric Quality of Life Inventory scores were improved after the intervention (-40.3%; P = 0.001 and -48.2%; P = 0.049, respectively). Importantly, after exercise, the Disease Activity Score was reduced (-26.9%; P = 0.026) and the Childhood Muscle Assessment Scale was improved (+2.5%; P = 0.009), whereas the Manual Muscle Test presented a trend toward statistical significance (+2.2%; P = 0.081). The peak oxygen consumption and time-to-exhaustion were increased by 13.3% (P = 0.001) and 18.2% (P = 0.003), respectively, whereas resting heart rate was decreased by 14.7% (P = 0.006), indicating important cardiovascular adaptations to the exercise program. Upper and lower extremity muscle strength and muscle function were also significantly improved after the exercise training (P < 0.05). Both the whole-body and the lumbar spine bone mineral apparent density were significantly increased after training (1.44%; P = 0.044 and 2.85%; P = 0.008, respectively). Conclusion. We showed for the first time that a 12-week supervised exercise program is safe and can improve muscle strength and function, aerobic conditioning, bone mass, disease activity, and health-related quality of life in patients with active and nonactive mild and chronic juvenile DM with near normal physical function and quality of life.

Experimental arthritis: effect on growth parameters and total skeletal calcium

Aim of the study was to investigate the possible mechanisms leading to stunted growth and osteoporosis in experimental arthritis. Fourty-two female rats of 7-8 weeks of age were randomly assigned to three groups of 14 animals each: (a) controls; (b) adjuvant-inoculated (AA); and (c) adjuvant-inoculated rats receiving 10 mg cyclosporin A (CsA) orally for 30 days. Biological parameters studied were: hindpaw swelling; vertebral length progression expressed as Delta increments between days 1 and 30 as a parameter of skeletal growth, and estimation of total skeletal mineral content by dual energy X-ray absorptiometry (n=10 each group) on day 30. Endocrine parameters measured were pulsatile release of growth hormone (rGH) on day 30 following jugular cannulation and measurement of insulin-like growth factor (IGF-1) in pooled plasma from rGH profiles. Results can be summarized as follows: Untreated AA rats exhibited local signs of inflammation in comparison with controls (hindpaw diameter 8.1-8.9 mm vs. 5.3-5.6 mm in controls). Treatment with CsA normalized this parameter (4.9-5.6 mm). Vertebral growth was significantly retarded in AA rats in comparison with controls (214+/-32 vs. 473+/-33 microm; p<0.001). Administration of CsA normalized vertebral size increment with a clear tendency to overgrowth (523+/-43 microm, n.s.). There was also a marked reduction in total skeletal mineral content in diseased (AA) rats as compared to controls (5.8+/-0.1 vs. 7.5+/-0.1g [OH-apatite]; p<0.001), and a moderate but significant increment above controls in the group receiving CsA (8.0+/-0.1 vs. 7.5+/-0.1g [OH-appatite]; p<0.04). Integrated rGH profiles exhibited a significant fall in arthritic rats and were completely restored to normal under CsA treatment. A trend toward higher rGH values was observed in the latter group (2908+/-554 in AA vs. 8317+/-1492 ng/ml/240 min in controls; p<0.001, and 10940+/-222 ng/ml/240 min, n.s. in the CsA group). There was a good correlation between skeletal growth and rGH pulsatility (r=0.81; p<0.001). IGF-1 followed a similar pattern (630+/-44 in AA vs. 752+/-30 ng/ml in controls; p<0.04, and 769+/-59 ng/ml in the CsA group, n.s. vs. controls). Thus, a clear tendency to skeletal overgrowth following treatment was observed in agreement with the hormonal data. It can therefore be concluded that, in experimental arthritis, attenuated GH-spiking and reduced circulating IGF-1 appear to be causally related to growth retardation, probably mimicking signs and symptoms observed in juvenile arthritis. Therapy with CsA is followed by normalization of hormonal and biological parameters accompanied by a catch up phenomenon in skeletal growth which is also observed clinically in juvenile arthritis. Generalized osteopenia is a prominent feature seemingly connected with the growth abnormalities as they parallel each other during the evolution of the disease and respond equally to therapy.

Características clínicas de las uveítis en pacientes pediátricos en dos centros de referencia oftalmológica en Bogotá

Introducción: La de uveítis pediátrica tiene una prevalencia mundial de aproximadamente 30 casos por 100.000 y constituye la segunda causa de ceguera en niños en Colombia. Sin embargo, no existen estudios que caractericen esta entidad en nuestro medio. Materiales y Métodos: Estudio retrospectivo, observacional, descriptivo, mediante la revisión de historias clínicas de pacientes pediátricos con diagnóstico de uveítis en la Fundación Oftalmológica Nacional y en un centro privado de consulta oftalmológica en Bogotá entre enero de 2000 y julio de 2013. Resultados: Se describe un total de 311 pacientes pediátricos con diagnóstico de uveítis, 51.8% niñas. La edad promedio de presentación fue de 10.1 años. La uveítis posterior fue la más frecuente (57.8%), siendo más común de aparición insidiosa (87.5%) y crónica (78.1%). La etiología más frecuente fue infecciosa (58.2%) causada por toxoplasmosis (76.8%). Se encontró una diferencia estadísticamente significativa entre la agudeza visual de la uveítis anterior (20/67) e intermedia (20/69), en comparación con la uveítis posterior (20/417) y panuveítis (20/209) (p <0,05). Discusión: Los datos de este estudio proporcionan el primer reporte de las características clínicas de la uveítis en pacientes pediátricos en Colombia, donde las uveítis infecciosas son la primera causa de esta entidad. Este estudio mejorará el conocimiento de la uveítis en nuestro medio, así como es un instrumento para el desarrollo de políticas públicas para la población pediátrica colombiana, con el fin de mejorar los resultados del tratamiento de estos pacientes.