Orientador: Claudia Saad Magalhães / Banca: Adriana Maluf Elias Sallum / Banca: José Eduardo Corrente / Resumo: Avaliar as propriedades clinimétricas do Juvenile Arthritis Damage Index (JADI), e de seus componentes articular (JADI - A) e extra-articular (JADI - E), em diferentes subtipos de Artrite Idiopática Juvenil (AIJ), caracterizando-se os danos e estabelecendo-se a probabilidade de dano articular e extra-articular durante o curso da AIJ. Uma avaliação transversal foi realizada em uma série de casos de AIJ, entre 2006 e 2008. Os dados clínicos e demográficos, exame articular, pontuação do JADI-A e JADI-E, compilação do Childhood Health Assessment Questionnaire (CHAQ) e das escalas visuais analógicas para dor e bem-estar global pelos pais e pelo médico, classificação funcional de Steinbrocker e avaliação radiológica foram realizados durante uma visita ambulatorial. A avaliação longitudinal retrospectiva foi realizada da primeira até última visita ao serviço (1997 a 2008), observando-se as medidas de desfecho e tratamento. As propriedades de medida do JADI-A e JADI-E foram correlacionadas ao desfecho e a probabilidade de dano analisada por meio de curva de sobrevida com cálculo do risco de dano anual. Foram incluídos cento e um casos de AIJ, classificados como oligoarticular persistente (68,3%), artrite relacionada à entesite (8,9%), oligoarticular estendido (7,9%), poliarticular fator reumatóide (FR) + (5,0%), sistêmica (5,0%), poliarticular FR - (4,0%) e artrite psoriásica (1%), idade de início 7,1 anos (0,9 - 14,2) e duração da doença 2,7 anos (0,3 - 18,6), 66,3% em atividade, ANA + em 46,5% e HLA-B27 + em 5%. Noventa e oito porcento receberam AINH, 21,8% corticosteróides, 50,5% corticosteróide intra-articular, 39,6% DMARD e 10,9% agentes biológicos. Oitenta e três porcento não apresentavam incapacidade funcional pela classificação de Steinbrocker, e 53% pelo CHAQ. Foram observados dano articular em 45,5% e extra-articular nem 37,6% dos casos... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: To assess clinimetric properties of the Juvenile Arthritis Damage Index (JADI) and its two components, articular (JADI-A) and extraarticular (JADI-E), in different subtypes of Juvenile Idiopathic Arthritis (JIA), in order to characterize the damage and to establish the probability of articular and extraarticular damage during the course of JIA. A cross-sectional evaluation in a JIA case series was carried out, between 2006 and 2008. The clinical and demographic data, joint assessment, JADI-A and JADI-E scoring, Childhood Health Assessment Questionnaire (CHAQ) scoring as well as physician's global assessment, pain and child's overall well-being by visual analog scale (VAS), Steinbrocker functional and radiographic assessments were assessed during a routine clinic visit. A retrospective longitudinal case-note revision was performed collecting data from the first to the last visit (1997 to 2008) for recording outcome measures and treatment. JADI-A and JADI-E measurement properties were correlated with outcome measures and the damage probability calculated by survival analysis alongside the damage risk calculated year by year. One hundred and one cases of JIA were included, classified as persistent oligoarthritis (68.3%), enthesitis-related arthritis (8.9%), extended oligoarthritis (7.9%), positive rheumatoid factor (RF) polyarthritis (5.0%), systemic arthritis (5.0%), negative RF polyarthritis (4.0%) and psoriatic arthritis (1.0%), age at onset 7.1 years (0.9 - 14.2), and disease duration 2.7 years (0.3 - 18.6), active disease in 66.3%, positive ANA in 46.5%, positive HLA-B27 in 5%. Ninety eight percent received NSAID, 21.8% corticosteroid, 50.5% intraarticular corticosteroid, 39.6% DMARD and 10.9% biologic agent. Eighty three percent did not have functional disability by Steinbrocker classification, and 53% baseline CHAQ. Overall, joint damage was observed in 45.5% and extraarticular... (Complete abstract click electronic access below) / Mestre

Objetivos: Avaliar associações da velocidade de crescimento com marcadores inflamatórios e dose cumulativa de glicorticóide em uma coorte de pacientes com Artrite Idiopática Juvenil acompanhados por 1 ano. Material e Métodos: Foram avaliados 79 pacientes com AIJ segundo critérios da ILAR. A atividade clínica da doença foi classificada por médicos reumatologistas pediátricos. Os dados antropométricos foram mensurados e classificados de acordo com as normas da Organização Mundial da Saúde. Foram utilizadas curvas de velocidade de crescimento segundo Tanner; considerou-se baixa velocidade de crescimento valores de escore Z ≤ -2. Concentrações séricas de IL-6 foram mensuradas por ELISA no período basal, e valores acima de 1 pg/ml foram considerados elevados. Resultados: Baixa velocidade de crescimento teve uma prevalência de 25,3% e esteve associada com atividade da doença no período do seguimento (p=0,085), valores elevados de IL-6 (interleucina-6) (p=0,003), velocidade de sedimentação globular (VSG) (p=0,022) e proteína C reativa (PCR) (p=0,001) e maior dosagem cumulativa de glicocorticóide (0=0,044). Na regressão linear múltipla tendo como variável dependente a velocidade de crescimento, observou-se que somente os níveis elevados de IL-6 foram independente e negativamente associados com a velocidade de crescimento (p=0,025). Conclusão: Baixa velocidade de crescimento é altamente prevalente em crianças com AIJ. Níveis elevados de IL-6 têm um importante impacto negativo no crescimento desses pacientes, enquanto a exposição ao glicocorticóide total parece ser um fator secundário. / Objective: To evaluate associations of growth velocity with inflammatory markers and cumulative dose of glucocorticoid in a cohort of patients with Juvenile Idiopathic Arthritis (JIA) followed during 1 year. Methods: Seventy-nine patients were evaluated by criteria according to the ILAR. The disease activity was evaluated by a pediatric rheumatologist. The anthropometic data were measured and classified according to the World Health Organization standards. Growth velocity curves were used according to Tanner, values below the Z-score ≤ -2 were considered low growth velocity. Serum concentrations of IL-6 were measured by ELISA in the baseline period, and values over 1pg/ml were considered as elevated. Results: The prevalence of low growth velocity was 25.3%, and it was associated with: active disease on follow-up visit (p=0,085), elevated interleukin-6 (IL-6) (p=0,003), erythrocyte sedimentation rate (ESR) (p=0,022) and C-reactive protein (CRP) (p=0,001) and higher cumulative glucocorticoid doses (0=0,044). In the multiple linear regression with growth velocity as the dependent variable, only elevated IL-6 levels were independently and negatively associated with growth velocity (p=0,025). Conclusion: Low growth velocity is highly prevalent in children with JIA. Elevated IL-6 levels seem to have an important negative impact on growth in these children, while total glucocorticoid exposure appears to be a secondary factor.

A Artrite idiopática juvenil (AIJ) é a artropatia crônica mais prevalente na infância e adolescência. A prevalência da síndrome metabólica, assim como da obesidade, vem apresentando um rápido aumento, atingindo todas as faixas etárias, incluindo a infância. A síndrome metabólica é caracterizada por um conjunto de riscos para doença cardiovascular e diabetes melito tipo 2, incluindo adiposidade abdominal, resistência à insulina, dislipidemias e hipertensão arterial sistêmica. Além destes componentes, a inflamação tem sido reconhecida cada vez mais como um fator importante na síndrome metabólica e obesidade, e pacientes com doenças caracterizadas por processos inflamatórios crônicos, como a AIJ, poderiam representar grupos de risco especiais. Os glicocorticoides são utilizados rotineiramente no controle da inflamação da artrite idiopática juvenil, em doses elevadas e com uso prolongado. O uso crônico do glicocorticoide pode induzir resistência à insulina, hipertensão arterial sistêmica e obesidade, aumentando o risco de desenvolver síndrome metabólica. O presente trabalho tem como objetivo avaliar a prevalência de obesidade e síndrome metabólica em pacientes com AIJ. Em pacientes acompanhados no Serviço de Reumatologia do Hospital de Clínicas de Porto Alegre (HCPA) e Hospital da Criança Santo Antônio (complexo Santa Casa) foram observados uma prevalência de 19,7% de síndrome metabólica e 22,7% de obesidade, sem diferença entre os subtipos da doença. A obesidade foi associada com tempo de duração da doença, obesidade abdominal, pressão arterial elevada, resistência à insulina e presença de síndrome metabólica. O IMC, circunferência da cintura, triglicerídeos, baixos níveis de HDL-c, pressão arterial sistólica e diastólica, níveis séricos de insulina e resistência a insulina (HOMA-ir) mostraram associação com a SM (p<0,05). Não houve associação entre a presença de SM e dose cumulativa de glicocorticoide, atividade da doença e tempo de duração da doença. Os resultados mostram uma alta frequência de obesidade e síndrome metabólica em pacientes com AIJ, sugerindo um aumento do risco de futuras complicações cardiovasculares. e parecem ser independentes do uso de glicocorticoide. Ações de intervenção são necessárias entre os pacientes com AIJ para reduzir o excesso de peso, evitar as complicações metabólicas e fatores de risco cardiovasculares na vida adulta. / Juvenile idiopathic arthritis is the most prevalent chronic arthropathy in childhood and adolescence. The prevalence of metabolic syndrome, as well as obesity, is increasing fast, in all age groups, including the childhood. Metabolic syndrome is defined as a cluster of risk factors for cardiovascular and type 2 diabetes, including abdominal obesity, insulin resistance, dyslipidaemia and hypertension. Besides these components, inflammation has been increasingly considered as a significant component in metabolic syndrome and obesity, and patients with diseases characterized by the presence of chronic inflammation, such as JIA, could represent special groups of risk. Glucocorticoids are used routinely in the management of the inflammation of JIA, in high doses and long-term. Long-term use of the glucocorticoids can cause insulin resistance, hypertension and obesity, increasing the risk for the metabolic syndrome. The aim of the present study was to evaluate prevalence of the obesity and metabolic syndrome in patients with juvenile idiopathic arthritis (JIA). In patients followed in the Hospital de Clínicas de Porto Alegre (HCPA) and Hospital da Criança Santo Antônio (Santa Casa Complex) service of reumatology were observed a prevalence of 19.7% of metabolic syndrome and 22.7% of obese, without difference between the subtypes of the disease. Obesity was associated with disease duration, abdominal obesity, arterial hypertension, insulin resistance and presence of metabolic syndrome. BMI, waist circunference, triglycerides, low HDL-c level, systolic and diastolic BP, fasting insulin serum levels and insulin resistance (HOMA-ir) showed significant association with MetS (p<0,05). There was no correlation between the presence of metabolic syndrome and cumulative glucocorticoid dose, disease activity and duration of disease. The results showed that there were high frequencies of obesity and metabolic syndrome in JIA patients and use appears to be indeoendent of the use glucocorticoid. Intervation actions are needed among JIA patients, to decrease excess weight, metabolic complications and cardiovascular risk factors in adulthood.

There is little head-to-head evidence comparing interventions available for juvenile idiopathic arthritis (JIA). This review involved a series of systematic reviews and network meta-analyses (NMAs) to evaluate the comparative efficacy and safety of pharmacological and non-pharmacological interventions among patients with JIA. Outcomes were the American College of Rheumatology Pediatric 30 (ACR Pedi 30) (disease response), its six composite outcomes, pain relief, health-related quality of life, and physical and emotional functioning. There was some evidence that etanercept had greater reduction in the number of joints with active arthritis compared to abatacept for polyarticular-course JIA and that canakinumab had improved ACR Pedi 30 over rilonacept. Non-pharmacological interventions showed no significant results for efficacy but were safe overall. Most included studies were low-quality and many were excluded from analysis because of unclear reporting or no results for outcomes of interest. As more studies are conducted this will improve the estimates from the NMAs.

Juvenile idiopathic arthritis, JIA, is used as an umbrella term covering a heterogeneous group of chronic arthritis forms in children, many of which have important differences compared to adult arthritis, while others possibly represent similar diseases among children and adults. Classification aims to give a better understanding of the pathogenesis, patterns, disease trajectories and treatment responses. For the juvenile psoriatic arthritis, JPsA, the classification criteria are currently being debated. The distribution of affected joints in JIA differs greatly and it is unknown why some joints appear to be more affected than others. The temporomandibular joint (TMJ) can be affected early in the course of the disease and often the symptoms are mild and without obvious swelling. This thesis has its origin in the Nordic Study Group of Paediatric Rheumatology and the population-based prospective study of 510 children with newly diagnosed JIA included between 1997 and 1999. Totally 440 children were included in the eight-year follow-up, and in the TMJ study 265 patients were examined and underwent cone-beam computed tomography, CBCT, 17 years after onset. After eight years a considerable proportion of the children with definite psoriasis were classified as undifferentiated JIA based on the exclusion criteria in the ILAR classification. Our data also presents the heterogenicity of JPsA and the development over time of clinical variables supporting a psoriatic diathesis, as well as the overlap between JPsA and enthesitis-related arthritis in a group of patients.  We found that extensive symptoms and dysfunctions of the TMJ are seen in JIA 17 years after disease onset, even in patients registered with inactive disease or remission. Individuals with substantial condylar damage on CBCT were found in all JIA categories. The deeper understanding of a chronic disease over time is crucial for research initiatives to improve care as well as for clinical decisions and planning of the health care. Our findings suggest a need for a more appropriate classification of JPsA and also that aspects of TMJ involvement should be included in the general health assessment in JIA.

No description available.

IntroductionChildren with juvenile idiopathic arthritis (JIA) are at risk of developing sight threatening JIAassociated uveitis (JIA-U). Swedish children with JIA are included in an ophthalmologicalscreening program, based on European studies, to ensure early detection and treatment of JIAU.AimThe aim of this study was to describe the prevalence, risk factors, clinical characteristics andassociated ocular complications of JIA-U and pharmacological therapy in a cohort of Swedishchildren with JIA. MethodsThe study was conducted as a retrospective review of medical records of children with JIAtreated at Örebro University Hospital, Sweden in 2010-2019, with a minimum of one year ofophthalmological follow-up.ResultsMedical records of 200 children with JIA were reviewed, of which 96 children were includedin the study. Uveitis was detected in 21/92 (22.8%) children. Boys developed uveitisproportionally more often than girls. JIA-U onset within the first four years after JIA diagnosisoccurred in 52.4% and onset occurred later in boys than in girls (p = 0.019). Oligoarthritis wasthe only significant risk factor for uveitis development (OR 3.111, 95% CI 1.029-9.409, p =0.044). Uveitis associated complications occurred in 7/21 (33.3%) children. ConclusionIn this regional cohort study, we found a higher prevalence of JIA-U, a higher proportion ofboys developing uveitis and a lower portion of children developing uveitis within the four yearsof high frequency screening compared to recent Swedish respectively European studies. Ourfindings indicated the need of future Swedish studies to revise and optimize the currentSwedish guidelines for ophthalmological JIA-U screening.

A 3 year old Hispanic male presented with fevers, skin rash, left neck swelling and refusal to walk of several days duration. Physical exam revealed a febrile, fussy toddler with a tender, cystic lesion in the left submandibular region. Both ankles had tender cystic lesions on the lateral malleolar regions. Labs: WBC 33,000 with neutrophilia, bandemia, thrombocytosis, and increased ESR and CRP. MRI of the neck and ankles revealed cystic lymphatic malformations with no communication with the joints.ENT specialist was consulted and neck cystic lesion was aspirated to rule out a septic focus. Bone scan of the lower extremities ruled out infectious or malignant etiology. He was started on multiple antibiotics with a presumed diagnosis of sepsis. An ECHO on the 4th hospital day showed a pericardial effusion which required a pericardial window. He also developed bilateral pleural effusions which resolved with supportive treatment. Aspirates from the cystic lesions, pericardial fluid, blood and urine cultures were sterile. Even in the second week of hospital stay, he continued to spike high fevers (Tmax 107) with high white counts and left shift inspite of treatment with antibiotics. A diagnosis of systemic onset juvenile idiopathic arthritis (SOJIA) was made with input from rheumatologist. Antibiotics were discontinued and steroids were started with good response. Cystic lesions were treated with percutaneous sclerotherapy with doxycycline. He was discharged home on oral steroids, NSAID’s and weekly methotrexate. Etanercept was added to decrease dependence on oral steroids. He remains in good health 2 years since initial presentation. Discussion: A febrile toddler who refuses to walk is a common clinical presentation in pediatrics. Differential diagnosis of such a patient includes osteomyelitis, septic arthritis, acute rheumatic fever, leukemia and non-accidental trauma. The presence of systemic extra-articular symptoms as in our patient must alert the pediatrician to systemic onset juvenile rheumatoid arthritis (SOJIA). It accounts for 10-20% of all juvenile idiopathic arthritis (JIA) patients with an incidence of 0.4-0.8 per 100,000. SOJIA differs from other conditions in its multisystem involvement. Clinical features like pleurisy, pericarditis, spiking fevers, hepatosplenomegaly and lymphadenopathy overshadow the joint symptoms. The joint involvement may be completely absent or may be a late clinical feature. These patients have leukocytosis, thrombocytosis and high inflammatory markers simulating a septic focus. In our patient, the accurate diagnosis was complicated by the confounding presence of multiple cystic lymphatic lesions. Treatment of SOJIA is challenging. Oral steroids, NSAID’s, methotrexate, etanercept and the newer anakinra have been used with varying success. Our case underlines the importance of considering a diagnosis of systemic onset JIA in a febrile toddler even in the absence of overt joint involvement.

Circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs) are sensitive markers of cardiovascular damage and repair, respectively. The aim of this thesis was to advance the state of knowledge regarding CECs and EPCs, and the factors affecting their concentrations, in children and adolescents. The first and second studies demonstrated that CECs and EPCs were similar when participants were split by sex, chronological age (8-10 vs. 14-16 years), and biological age (≤ -1 vs. ≥ +1 year from peak height velocity). Moreover, CECs, but not EPCs, were positively associated with aerobic fitness and negatively related to daily moderate-to-vigorous physical activity. Neither CECs nor EPCs were related to level of adiposity. Although there was a large degree of inter-individual variability in both cell types, most of our data were clustered towards one end of the reported range. These observations highlighted the need to examine these cells in children with chronic conditions associated with an increased risk of poor cardiovascular health. Therefore, CECs and EPCs were examined at rest and in response to acute exercise in juvenile idiopathic arthritis (JIA) and healthy controls. Resting levels of CECs and EPCs were similar in both groups, which may be attributable to the low disease activity in the participants with JIA. High intensity, intermittent exercise (HIIE) and moderate intensity, continuous exercise (MICE) had no effect on CECs in both groups. Conversely, MICE led to a robust increase in EPCs in healthy controls; no such change was observed in youth with JIA. This thesis represents the first comprehensive assessment of CECs and EPCs in the context of fitness, physical activity, and acute exercise in children and adolescents. Future research should examine the function and fate of these cells in youth, as well as the potential mechanisms underlying the blunted EPC response to exercise in JIA. / Thesis / Doctor of Philosophy (PhD) / Fitness and physical activity are critical for maintaining and improving cardiovascular health in children and adults. We don’t know exactly how they do this but the evidence in adults suggests it may be related to rare cells in the blood involved in repairing damaged blood vessels. The main objective of this thesis was to learn more about these cells, called circulating endothelial cells and endothelial progenitor cells, in children. We found that only circulating endothelial cells were related to fitness and physical activity. We also found that endothelial progenitor cells increased when healthy children performed 60 minutes of cycling. On the other hand, these cells did not change when children with juvenile idiopathic arthritis performed the same exercise. More research is needed to determine exactly why these cells responded to exercise in healthy but not sick children, and to help us identify the optimal exercise to improve these cells in youth.

No description available.