Sandra Helena Machado

Growth Velocity and Interleukin 6 Concentrations in Juvenile Idiopathic Arthritis

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. Disease activity was evaluated by a pediatric rheumatologist. Anthropometric data were classified according to the World Health Organization standards. Tanner growth velocity curves were used; values below the Z-score≤ −2 were considered low growth velocity. Serum concentrations of interleukin 6 (IL-6) were measured by ELISA, and values > 1 pg/ml were considered elevated. Results The prevalence of low growth velocity was 25.3%, and it was associated with active disease on followup visit, elevated IL-6, erythrocyte sedimentation rate and C-reactive protein, and higher cumulative glucocorticoid doses. In the multiple linear regression with growth velocity as the dependent variable, only elevated IL-6 level was independently and negatively associated with growth velocity. Conclusion Low growth velocity is highly prevalent in children with JIA. Elevated IL-6 levels seem to have an important negative influence on growth in these children, while total glucocorticoid exposure appears to be a secondary factor.

Prevalência de anticorpos contra peptídeos cíclicos citrulinados na artrite idiopática juvenil

OBJETIVOS: Avaliar a presenca de anticorpos contra peptideos ciclicos citrulinados em uma coorte de pacientes com artrite idiopatica juvenil. METODOS: A presenca de anticorpos contra peptideos ciclicos citrulinados foi avaliada por ensaio imunoenzimatico (ELISA) no soro de pacientes com artrite idiopatica juvenil com idade inferior a 18 anos, acompanhados no ambulatorio de reumatologia pediatrica do Hospital de Clinicas de Porto Alegre, com tempo de diagnostico de doenca de, no minimo, 6 meses. Tambem foi estudada a presenca do fator reumatoide IgM e do fator antinuclear em celulas Hep-2 RESULTADOS: Foram analisadas amostras sericas de 45 pacientes com artrite idiopatica juvenil. A presenca de titulos elevados de anticorpos contra peptideos ciclicos citrulinados foi encontrada somente no soro de uma crianca (2%), a qual apresentava quadro de poliartrite com fator reumatoide reagente. CONCLUSOES: O anticorpo contra peptideos ciclicos citrulinados pode ser detectado em criancas com artrite idiopatica juvenil, mas em frequencia muito inferior aos adultos com artrite reumatoide. Torna-se importante avaliar se anticorpos contra peptideos ciclicos citrulinados podem identificar os pacientes com artrite idiopatica juvenil com potencial de evolucao para artrite reumatoide do adulto.

[The prevalence of anti-cyclic citrullinated peptide antibodies in juvenile idiopathic arthritis].

OBJECTIVES To assess the presence of anti-cyclic citrullinated peptide antibodies in a cohort of patients with juvenile idiopathic arthritis. METHODS Anti-cyclic citrullinated peptide antibodies was tested for with an enzyme linked immunoabsorbent assay (ELISA) in serum samples of patients from the Hospital de Clínicas de Porto Alegre, all less than 18 years old and with previous diagnosis for at least 6 months. IgMRF (rheumatoid factor) and antinuclear antibodies in Hep-2 cells were also assayed. RESULTS Serum samples were analyzed from 45 patients. The presence of high levels of anti-cyclic citrullinated peptide antibodies was found in the serum of just one child (2%), who presented sero-positive polyarthritis. CONCLUSIONS Anti-cyclic citrullinated peptide antibodies can be detected in children with juvenile idiopathic arthritis, but much less frequently than in adults with rheumatoid arthritis. It still remains to be determined whether anti-cyclic citrullinated peptide antibodies can identify a subset of juvenile idiopathic arthritis patients with the potential to progress to adult rheumatoid arthritis.OBJECTIVES: To assess the presence of anti-cyclic citrullinated peptide antibodies in a cohort of patients with juvenile idiopathic arthritis. METHODS: Anti-cyclic citrullinated peptide antibodies was tested for with an enzyme linked immunoabsorbent assay (ELISA) in serum samples of patients from the Hospital de Clínicas de Porto Alegre, all less than 18 years old and with previous diagnosis for at least 6 months. IgMRF (rheumatoid factor) and antinuclear antibodies in Hep-2 cells were also assayed. RESULTS: Serum samples were analyzed from 45 patients. The presence of high levels of anti-cyclic citrullinated peptide antibodies was found in the serum of just one child (2%), who presented sero-positive polyarthritis. CONCLUSIONS: Anti-cyclic citrullinated peptide antibodies can be detected in children with juvenile idiopathic arthritis, but much less frequently than in adults with rheumatoid arthritis. It still remains to be determined whether anti-cyclic citrullinated peptide antibodies can identify a subset of juvenile idiopathic arthritis patients with the potential to progress to adult rheumatoid arthritis.

Metabolic syndrome and juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is the most prevalent chronic arthropathy in childhood and adolescence. The prevalence of metabolic syndrome, as well as obesity, is increasing rapidly in all age groups, including children. Metabolic syndrome is defined as a cluster of risk factors for cardiovascular disease and type 2 diabetes mellitus, including abdominal obesity, insulin resistance, dyslipidemia and hypertension. Besides those components, inflammation has been increasingly considered as a significant component of metabolic syndrome and obesity, and patients with diseases characterized by the presence of chronic inflammation, such as JIA, could represent special risk groups. 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 to insulin resistance, hypertension, and obesity, increasing the risk of metabolic syndrome. The aim of this study is to review the literature on the prevalence of different components of metabolic syndrome in patients with JIA. We observed that the data on metabolic syndrome and its components in those patients are very scarce and more studies needed, in view of the potential increased risk of cardiovascular disease.

Safety of tocilizumab in the treatment of juvenile idiopathic arthritis

ABSTRACT Introduction: Tocilizumab (TCZ) is a recombinant humanized monoclonal antibody and IL-6 receptor antagonist, currently approved for the treatment of systemic juvenile idiopathic arthritis (sJIA) and polyarticular juvenile idiopathic arthritis (pJIA) in children aged 2 years or older refractory to conventional treatment. The most common adverse events in patients treated with TCZ were infections, especially in the respiratory tract. The most frequent laboratory abnormalities were altered liver function, neutropenia and elevated cholesterol levels. Areas covered: The safety of TCZ in the treatment of children with JIA was determined based on a review of published clinical trials, including two multicenter studies of patients with sJIA and pJIA (the TENDER and CHERISH trials, respectively). The frequency of adverse events (AEs), serious adverse events (SAEs) and deaths reported in these studies was analyzed and discussed. Expert opinion: TCZ was effective and well tolerated in the treatment of severe forms of sJIA and pJIA, and can be considered a treatment of choice for these conditions. The risk of infections and laboratory abnormalities, such as neutropenia, should be constantly monitored. There is still a need for comparative studies of the risks and benefits of biological agents in patients with refractory JIA.

Impacto da atividade inflamatória e uso de glicocorticóide nas variáveis nutricionais da artrite idiopática juvenil

OBJECTIVE: To assess the nutritional status in juvenile idiopathic arthritis (JIA) and the influence of inflammatory activity and glucocorticoid use. METHODS: One hundred and sixteen patients were evaluated. Disease subtype and disease activity were defined by the attending physician, and the cumulative glucocorticoid dose was recorded by chart review. The percentiles of body mass index (BMI) and triceps skinfold (TSF) and the Z-score for height were determined: low weight and low adiposity were diagnosed when BMI and TSF were below the 5th percentile. Short stature was defined by a Z-score of height for age < -2. The serum level of IGF-I was measured by radioimmunoassay. RESULTS: The prevalences of low weight, low adiposity and short stature were 16.4%, 20.7% and 10.4%, respectively. Low IGF-1 serum level was found in 14 patients (12.1%). The factors negatively associated with the Z-score of height in multivariable regression analysis were disease duration (partial correlation coefficient, 95% confidence interval: -0.370, -0.527 to -0.188; p < 0.001), erythrocyte sedimentation rate (ESR) (-0.357, -0.516 to -0.174; p < 0.001), polyarticular or systemic subtype (-0.290, -0.459 to -0.100; p = 0.003), while there was no significant association with the cumulative dose of glucocorticoids (0.086, -0.111 to 0.277; p = 0.391). None of these variables were significantly associated with the percentiles of BMI or TSF, but patients with a systemic or polyarticular subtype tended to present lower percentiles of BMI (p = 0.051). CONCLUSIONS: Nutritional status is frequently compromised in JIA. The duration and subtype of the disease and the ESR are factors independently associated with short stature. The cumulative dose of glucocorticoids was not independently associated with short stature or other nutricional variables.

Height and sexual maturation in girls with juvenile idiopathic arthritis

OBJECTIVE To evaluate height, sexual maturation, and the difference between final and expected height in girls with juvenile idiopathic arthritis and no glucocorticoid treatment for at least six months, as compared to a group of healthy girls. METHODS This cross-sectional study involved 44 girls with juvenile idiopathic arthritis, diagnosed according to the International League of Associations for Rheumatology criteria, and 59 healthy controls aged between 8 and 18 (incomplete) years with no comorbid chronic diseases. Demographic data were collected from all participants, and disease and treatment variables were compiled for the patient group. Anthropometric measurements were converted into Z-scores based on World Health Organization standards. Sexual maturation was classified according to Tanner stages. RESULTS Body mass index and height Z-scores were lower in girls with juvenile idiopathic arthritis as compared to control participants. These values differed significantly in Tanner stage II. Three (6.8%) girls with juvenile idiopathic arthritis had height-for-age Z-scores <-2 (short stature). Girls with polyarticular juvenile idiopathic arthritis and higher cumulative glucocorticoid doses were significantly more likely to present with short stature. The percentage of prepubertal girls in the juvenile idiopathic arthritis group was significantly higher than that observed in the control group, (p=0.012). Age of menarche, adult height, and the difference between actual and expected height did not differ between groups. CONCLUSION These findings suggest that even six months after the suspension of glucocorticoid treatment, children with polyarticular/systemic juvenile idiopathic arthritis subtypes are still susceptible to low height and delayed puberty.

Growth Velocity and Interleukin 6 Concentrations: Applications to Juvenile Idiopathic Arthritis

Juvenile idiopathic arthritis (JIA) is the most common chronic pediatric rheumatic disease characterized by chronic inflammation and an important cause of growth disorders. The etiology of growth failure in children with JIA is multifactorial; however, inflammatory response seems to have an important role in impaired growth in these children. An imbalance of proinflammatory cytokines can be seen in children with inflammatory diseases. Scientific evidence has shown that proinflammatory cytokines, such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF-α), are important mediators of chronic inflammation in JIA. IL-6 has multiple biologic activities that could contribute to the systemic and local symptoms observed in patients with JIA. The objective of this chapter is to present relations between interleukin-6 actions and its influence on growth in children with JIA and other inflammatory diseases. We have prospectively evaluated the growth velocity in a cohort of patients with JIA followed for 1 year and its possible correlations with inflammatory markers and cumulative dose of glucocorticoid. The prevalence of low growth velocity was 25.3%, and it was associated with active disease, elevated IL-6 (interleukin-6) serum levels, high ESR (erythrocyte sedimentation rate) and CRP (C-reactive protein) levels, and higher cumulative glucocorticoid doses. Elevated IL-6 levels seem to have a major negative impact on growth in these children, while total glucocorticoid exposure appears to be a secondary factor. Short stature is frequent and it is a clinically important issue in children with other chronic diseases, and therefore it would be interesting to study IL-6 levels in these diseases. We think that aggressive control of inflammation, including resorting to inhibition of proinflammatory cytokines, rather than limiting glucocorticoid exposure, should be a priority to preserve growth in JIA patients.