Vitamin D Levels and Risk of Juvenile Idiopathic Arthritis: A Mendelian Randomization Study.

OBJECTIVES: Observational studies report mixed findings regarding the association between vitamin D and juvenile idiopathic arthritis (JIA) incidence or activity; however, such studies are susceptible to considerable bias. Because low vitamin D levels are common within the general population and easily corrected, there is potential public health benefit in identifying a causal association between vitamin D insufficiency and JIA incidence. To limit bias due to confounding and reverse causation, we examined the causal effect of the major circulating form of vitamin D, 25-hydroxy vitamin D (25-[OH]D), on JIA incidence using Mendelian randomization (MR). METHODS: In this 2-sample MR analysis, we used summary level data from the largest and most recent genome-wide association study of 25-(OH)D levels (sample size 443,734), alongside summary data from 2 JIA genetic studies (sample sizes 15,872 and 12,501), all from European populations. To test and account for potential bias due to pleiotropy, we employed multiple MR methods and sensitivity analyses. RESULTS: We found no evidence of a causal relationship between genetically predicted 25-(OH)D levels and JIA incidence (odds ratio 1.00 [95% confidence interval (95% CI) 0.76, 1.33] per SD increase in standardized natural-log transformed 25-[OH]D levels). This estimate was consistent across all methods tested. Additionally, there was no evidence that genetically predicted JIA causally influences 25-(OH)D levels (-0.002 SD change in standardized natural-log transformed 25-[OH]D levels per doubling odds in genetically predicted JIA [95% CI -0.006, 0.002]). CONCLUSION: Given the lack of a causal relationship between 25-(OH)D levels and JIA, population level vitamin D supplementation is unlikely to reduce JIA incidence.

[Therapeutic options in juvenile idiopathic arthritis : Surgical and conservative orthopedic rheumatological treatment]. / Therapeutische Optionen bei juveniler idiopathischer Arthritis : Operative und konservative orthopädisch-rheumatologische Behandlung.

The treatment of juvenile idiopathic arthritis (JIA) has made substantial progress within the last 25 years. Modern medicinal treatment enables inflammatory activity of the disease to be controlled in most of the cases. Mutilating courses of disease, which were formerly the rule have now become the exception. Today remission of disease is the aim of pediatric rheumatological treatment. Apart from effective control of inflammation this includes complete restoration of functional abilities of affected joints and the surrounding structures also affected. To achieve this goal a holistic and foresighted view of each patient's course is required. Therefore, even in an apparently uncomplicated course of disease in some cases of JIA it is advisable to plan an early interdisciplinary consultation including the pediatric rheumatologist and the orthopedic surgeon, in order to discuss an early surgical intervention, which can then be carried out in a timely manner, if necessary. This article provides an overview of the orthopedic rheumatological indications and options.

Assessment and treatment of Down syndrome-associated arthritis: a survey of pediatric rheumatologists.

BACKGROUND: Inflammatory arthritis in children with Down syndrome (DS) was first described in 1984 and is now termed Down syndrome-associated arthritis (DA). Studies have shown that DA is under-recognized with a 19-month average delay in diagnosis. Additionally, most patients present with polyarticular, rheumatoid factor (RF) and anti-nuclear antibody (ANA) negative disease. Current therapies for juvenile idiopathic arthritis (JIA) have been used, but appear to be poorly tolerated, more toxic and less effective in patients with DA. There is currently no standardized approach to the assessment or management of DA. The objective of this study was to describe provider perspectives toward diagnostic and treatment approach of DA, to provide baseline information upon which to design future studies. METHODS: An electronic survey, organized into sections regarding individual practices of assessment and treatment approach of DA, was sent to the Pediatric Rheumatology electronic list-serv. Survey responses were voluntary and results were analyzed by descriptive statistics. RESULTS: Of 90 survey responses received, 89 were included in the analysis (one was a duplicate response). The respondents were mostly pediatric rheumatologist (94%), with greater than 10 years of experience (55%). The majority (64%) currently see 1-3 patients with DA. Most view DA as the same disease as JIA (73%), and the majority (63%) use a combination of history, exam and imaging to diagnose DA. The most ordered diagnostic tests are CBC (97%) and ESR (96%). The most used treatments include NSAIDs (94%) and methotrexate (91%) followed by anti-TNF agents (90%). Methotrexate is most administered by subcutaneous route (84%) at a dose of 15 mg/m2 (56%). Oral corticosteroids were only used in 19% of the patients with DA. CONCLUSION: This is the first study to evaluate provider perspectives towards the diagnostic and treatment approach of DA. Most pediatric rheumatologists feel that DA and JIA are synonymous, and similar approaches to diagnosis are employed, utilizing history, physical exam, laboratory tests, and imaging modalities. DA is treated similarly to JIA with initiation of NSAIDs, disease-modifying anti-rheumatic drugs and biologic therapy. More research is needed to determine optimal screening and therapeutic approach specific to DA.

Medical pathways of children with juvenile idiopathic arthritis before referral to pediatric rheumatology centers.

OBJECTIVE: A better understanding about the referral pathway of patients suffering from juvenile idiopathic arthritis (JIA) is required The aim of this study was to describe and analyze time from onset of symptoms to first pediatric rheumatology (PR) visit and the referral pathway of children with incident JIA in two French competence centers. METHODS: From October 2009 to October 2017, new JIA patients were registered in the "Auvergne-Loire cohort on JIA". We collected referral pathway, symptom onset, biological and clinical data at first assessment in PR department. RESULTS: In all, 111 children were included. Median time to first PR visit was 3.3 months [interquartile range (IQR) 1.3, 10.7] with a significant difference between JIA subtypes. After exclusion of systemic JIA, older age at onset of symptoms, and presence of enthesitis or joint pain were significantly associated with a longer time to first PR visit, while joint swelling or limping, abnormal ESR or CRP were associated with a shorter time. The median number of health care practitioners met was 3 [IQR 3, 4]. Orthopedists referred children to a PR center in 64% of cases, pediatricians in 50%, emergency care practitioners in 27% and general practitioners in 25%. Although non-systemic JIAs are not an emergency, 45% were referred to the emergency room. CONCLUSION: Time to first PR visit is rather short compared to other countries but remains too long. Pediatric rheumatologists should offer primary care providers basic training on JIA and fast direct access to PR departments if JIA is suspected.

Therapeutic advances in juvenile idiopathic arthritis - associated uveitis.

PURPOSE OF REVIEW: The aim of this review is to highlight recent changes in the treatment of juvenile idiopathic arthritis (JIA) - associated uveitis in the era of biologics. RECENT FINDINGS: Early introduction of steroid-sparing therapies is paramount for appropriate management. Biologic therapies have improved the therapeutic management of JIA-uveitis and adalimumab is currently approved for pediatric-onset noninfectious chronic anterior uveitis with an inadequate response to topical steroids and methotrexate. Recent studies suggest that ocular complications in JIA-uveitis are less frequent compared with previous publications. However, patients with JIA-uveitis seem to be particularly dependent on classical immunosuppressive drugs or biologics. Indications for primary lens implantation have expanded considerably with the evolution of materials and better control of inflammation with biologics. The rate of serious adverse events related to new therapeutic approaches seem acceptable, however longer term follow-up is necessary. SUMMARY: Improvement in the initial screening and improved inflammation control with biologics has considerably reduced the potentially sight-threatening prognosis of JIA-uveitis.

Persistence and adverse events of biological treatment in adult patients with juvenile idiopathic arthritis: results from BIOBADASER.

BACKGROUND: Biologic therapy has changed the prognosis of patients with juvenile idiopathic arthritis (JIA). The aim of this study was to examine the pattern of use, drug survival, and adverse events of biologics in patients with JIA during the period from diagnosis to adulthood. METHODS: All patients included in BIOBADASER (Spanish Registry for Adverse Events of Biological Therapy in Rheumatic Diseases), a multicenter prospective registry, diagnosed with JIA between 2000 and 2015 were analyzed. Proportions, means, and SDs were used to describe the population. Incidence rates and 95% CIs were calculated to assess adverse events. Kaplan-Meier analysis was used to compare the drug survival rates. RESULTS: A total of 469 patients (46.1% women) were included. Their mean age at diagnosis was 9.4 ± 5.3 years. Their mean age at biologic treatment initiation was 23.9 ± 13.9 years. The pattern of use of biologics during their pediatric years showed a linear increase from 24% in 2000 to 65% in 2014. Biologic withdrawal for disease remission was higher in patients who initiated use biologics prior to 16 years of age than in those who were older (25.7% vs 7.9%, p < 0.0001). Serious adverse events had a total incidence rate of 41.4 (35.2-48.7) of 1000 patient-years. Patients younger than 16 years old showed significantly increased infections (p < 0.001). CONCLUSIONS: Survival and suspension by remission of biologics were higher when these compounds were initiated in patients with JIA who had not yet reached 16 years of age. The incidence rate of serious adverse events in pediatric vs adult patients with JIA treated with biologics was similar; however, a significant increase of infection was observed in patients under 16 years old.

Juvenile Idiopathic Arthritis.

Juvenile idiopathic arthritis is the most common chronic rheumatic disease of unknown aetiology in childhood and predominantly presents with peripheral arthritis. The disease is divided into several subgroups, according to demographic characteristics, clinical features, treatment modalities and disease prognosis. Systemic juvenile idiopathic arthritis, which is one of the most frequent disease subtypes, is characterized by recurrent fever and rash. Oligoarticular juvenile idiopathic arthritis, common among young female patients, is usually accompanied by anti-nuclear antibodie positivity and anterior uveitis. Seropositive polyarticular juvenile idiopathic arthritis, an analogue of adult rheumatoid arthritis, is seen in less than 10% of paediatric patients. Seronegative polyarticular juvenile idiopathic arthritis, an entity more specific for childhood, appears with widespread large- and small-joint involvement. Enthesitis-related arthritis is a separate disease subtype, characterized by enthesitis and asymmetric lower-extremity arthritis. This disease subtype represents the childhood form of adult spondyloarthropathies, with human leukocyte antigen-B27 positivity and uveitis but commonly without axial skeleton involvement. Juvenile psoriatic arthritis is characterized by a psoriatic rash, accompanied by arthritis, nail pitting and dactylitis. Disease complications can vary from growth retardation and osteoporosis secondary to treatment and disease activity, to life-threatening macrophage activation syndrome with multi-organ insufficiency. With the advent of new therapeutics over the past 15 years, there has been a marked improvement in juvenile idiopathic arthritis treatment and long-term outcome, without any sequelae. The treatment of juvenile idiopathic arthritis patients involves teamwork, including an experienced paediatric rheumatologist, an ophthalmologist, an orthopaedist, a paediatric psychiatrist and a physiotherapist. The primary goals of treatment are to eliminate active disease, to normalize joint function, to preserve normal growth and to prevent long-term joint damage. Timely and aggressive treatment is important to provide early disease control. The first-line treatment includes disease-modifying anti-rheumatic drugs (methotrexate, sulphasalazine, leflunomide) in combination with corticosteroids, used in different dosages and routes (oral, intravenous, intra-articular). Intra-articular application of steroids seems to be an effective treatment modality, especially in monoarthritis. Biological agents should be added in the treatment of unresponsive patients. Anti-tumour necrosis factor agents (etanercept, infliximab, adalimumab), anti-interleukin-1 agents (anakinra, canakinumab), anti- interleukin-6 agents (tocilizumab) and T-cell regulatory agents (abatacept) have been shown to be safe and effective in childhood patients. Recent studies reported sustained reduction in joint damage with even complete clinical improvement in paediatric patients, compared to previous data.

Management of Children with Juvenile Idiopathic Arthritis.

Juvenile idiopathic arthritis (JIA) comprises a group of heterogeneous disorders of chronic arthritis in childhood and remains the commonest pediatric rheumatic disease associated with significant long-term morbidity. Advances in understanding of the pathogenesis, better definition of disease control/remission measures, and the arrival of biological agents have improved the outcomes remarkably. Methotrexate (Mtx) remains the first-line disease modifying (DMARD) therapy for most children with JIA due to its proven efficacy and safety. Sulphosalazine (SSz) (especially for enthesitis) and leflunomide may also have a secondary role. Tumor necrosis factor inhibitors (TNF-I), alone or in combination with Mtx have shown tremendous benefit in children with polyarticular JIA, enthesitis related arthritis (ERA) and psoriatic arthritis. Tocilizumab appears very efficacious in systemic arthritis and abatacept and tocilizumab also appear to benefit polyarticular JIA; the role of rituximab remains unclear, though clearly beneficial in adult RA. TNF-I with Mtx is also effective in uveitis associated with JIA. Biologicals have demonstrated an impressive safety record in children with JIA, although close monitoring for rare but potentially dangerous adverse events, such as tuberculosis and other infections; paradoxical development of additional autoimmune diseases; and possibly an increased risk of cancers is warranted.

Diagnostic potential of hepcidin testing in pediatrics.

OBJECTIVES: Hepcidin, a peptide hormone released by hepatocytes into circulation is the main regulator of dietary iron absorption and cellular iron release. Although commercial tests are available, assay harmonization for hepcidin has not been yet reached, making reference intervals and consequent clinical decisions still elusive for each assay and specific population. The aim of this study is to set up hepcidin measurement in pediatric age and to investigate its potential usefulness in the diagnosis and management of iron disorders in children. METHODS: Serum hepcidin was measured by using an automated commercial immunoassay. Reference values were obtained from 86 healthy children. Hepcidin was then evaluated in 52 children with diseases where this hormone was expected to be differently regulated. RESULTS: Hepcidin values were 43.6 ng/mL median; 32-52.7 1-3 q: in males and 36.4 ng/mL median; 28.5-45.7 1-3 q: in females (P = 0.039). Hepcidin was significantly higher in postpubertal normal females than in normal males. Hepcidin resulted up-regulated in anemia of chronic disease of children affected by systemic Juvenile Idiopathic Arthritis and decreased after treatment with anakinra, an anti-interleukin-1 receptor antagonist. In iron deficiency anemia patients on oral iron supplementation and in ß-thalassemia subjects, hepcidin levels were similar to those found in healthy subjects. CONCLUSIONS: This study sets up reference values for pediatric population and shows that in normal controls serum hepcidin react differently to puberty in females vs. males. In addition, it suggests that serum hepcidin may discriminate microcytic inflammatory anemia of Juvenile Idiopathic Arthritis from iron deficiency anemia. Overall these findings may represent a helpful tool for future studies tailored to understand the role of hepcidin in management of iron disorders in children.

La artritis idiopática juvenil y su relevancia dentro de las enfermedades reumatológicas de la infancia / Juvenile idiopathic arthritis and its relevance in rheumatological diseases of children

El dolor y la inflamación que afecta a las articulaciones o tejidos periarticulares son motivo frecuente de consulta a nivel pediátrico. Dentro de los diagnósticos diferenciales se encuentran las enfermedades reumatológicas. En los últimos años ha cambiado el pronóstico y visión que se tenía de estas enfermedades gracias a los nuevos conocimientos sobre la patogenia y a la incorporación de nuevas terapias con agentes biológicos, basados en anticuerpos monoclonales y que se ha traducido en un cambio en los tratamientos convencionales de estas enfermedades. La Artritis Reumatoidea Juvenil, actualmente denominada Artritis Idiopática Juvenil (AIJ), constituye la enfermedad más frecuente dentro del espectro de estos cuadros autoinmunes. El objetivo de esta presentación es dar a conocer las diversas formas de AIJ y los principales hallazgos clínicos y de laboratorio que pueden orientar al clínico acerca de estas enfermedades y así iniciar un tratamiento oportuno que asegure un buen pronóstico de la enfermedad.

Musculoskeletal pain, joint pain and arthritis are a common complaint in pediatric practice. Among the differential diagnosis for these conditions are rheumatic diseases. Treatment and outcome of these conditions has greatly improved in recent years due to advances in the knowledge of the underlying mechanisms and the development of new therapies with biologic agents, based on monoclonal antibodies. These new therapies have changed the outcome and vision of these diseases. Among the different rheumatologic diseases described in children, Juvenile Rheumatoid Arthritis, now called Juvenile Idiopathic Arthritis (JIA), is the most common disease within the spectrum of autoimmune conditions. The aim of this presentation is to show the different forms of JIA and the main clinical and laboratory findings that can guide the clinician to an early diagnosis and initiate a timely treatment that can guarantee a better prognosis.

The clinical spectrum of juvenile idiopathic arthritis in a large urban population.

Urban populations present particular challenges for medical providers. Patients are extremely diverse, with varied socioeconomic, cultural, and ethnic backgrounds. Physicians caring for children with juvenile idiopathic arthritis must be prepared to interact effectively with many types of families who bring with them varied experiences and expectations. Pediatric rheumatologists should be familiar with patient characteristics that can influence disease outcomes. Access to care is affected by place of residence, referral delays, parental education, and the child's insurance status. Patients of different ethnic backgrounds vary in their trust of physicians and health systems. Understanding of risk in medical decision making is influenced by ethnicity as well. Adherence also varies by ethnic group, with African American patients reporting lower adherence than Caucasian patients. Issues of doctor­ patient communication and use of complementary and alternative medicine are also affected by cultural factors. Especially for physicians working in a large metropolitan area, an understanding of societal factors influencing patient behavior is essential to provide optimal care for children with juvenile idiopathic arthritis.

Juvenile idiopathic arthritis: new insights into classification, measures of outcome, and pharmacotherapy.

Significant advances have taken place in recent years in our understanding of the aetiopathogenesis, management, and clinical outcome of juvenile idiopathic arthritis (JIA). Fundamental to this advancement has been international collaborative efforts of the clinical scientific community and all those involved in the multidisciplinary care of children and young people with JIA. A key factor has been facing the challenge of developing a robust classification system for JIA, a clinically very heterogeneous group of conditions. JIA illustrates the necessity of disease classification to enable scientific progress but also the iterative and evolving process this entails. What is emerging is the imperative to improve our understanding of the biologic and genetic basis of JIA to underpin classification systems. Growing emphasis is centered on improved holistic care and outcome of children and young people with JIA. The expectation of patients, their families, and clinicians is the goal of inactive disease, remission off treatment, and the health and psychosocial well-being of young people emerging into adulthood. Validated tools that reflect these challenges are being developed, including those measuring disease improvement, flare, remission and minimal disease activity, health-related quality of life, and composite scores of activity and damage. Clinical research networks have driven success in developing an evidence-base for the treatment of JIA. Randomized comparative trials have demonstrated the benefit of early use of intra-articular corticosteroid injections, and the importance of methotrexate as the first-line, disease-modifying antirheumatic drug in JIA. The introduction of biologic therapies has opened a major new epoch in the medical management of JIA, with recent trials published on etanercept, infliximab, adalimumab, abatacept, tocilizumab, and anakinra. This review focuses on recent advances in JIA, especially developments in its classification, validation of appropriate measures of holistic outcome, and the specific contribution of established and newer pharmacologic agents available for treating children and young people.

[Methotrexate in the therapy of juvenile idiopathic arthritis]. / Methotrexat bei der Therapie der juvenilen idiopathischen Arthritis.

Treatment with low-dose methotrexate (MTX) is an important element in the therapy of juvenile idiopathic arthritis (JIA). It could be demonstrated in placebo-controlled trials that MTX is a safe and effective drug which is generally well tolerated by children and adolescents. MTX is usually used at a dose of 10-15 mg/m(2)/week, whereby oral administration is preferred for children. Side effects occur mainly in the form of gastro-intestinal discomfort such as nausea and vomiting or raised transaminases, which can be effectively treated with folic-acid supplementation.There are no general recommendations to date regarding in particular duration and discontinuation of MTX treatment or combination treatment with other disease-modifying antirheumatic drugs or biologics. These unresolved questions are the subject of current trials in which biomarkers have an increasingly important role.

Interferón gamma recombinante como alternativa terapéutica en niños con artritis idiopática juvenil / Recombinant gamma Interferon as a therapeutical alternative in children with juvenile idiopathic arthritis

INTRODUCCIÓN. La artritis idiopática juvenil (AIJ) es una enfermedad del colágeno caracterizada por sinovitis crónica y síntomas extraarticulares, de inicio antes de los 16 años de edad. El interferón gamma (INFγ) mostró eficacia en un ensayo anterior con pacientes resistentes o intolerantes a las otras terapias disponibles, por lo que se decidió evaluar su eficacia y seguridad como medicamento modificador de la evolución de esta enfermedad. MÉTODOS. Se realizó un ensayo clínico abierto, no controlado, en el que se administró INFγ por vía intramuscular en dosis de 50 000 UI/kg (hasta 1 x 10(6) UI) durante 2 años. En el ensayo se incluyeron 20 pacientes con AIJ: 5 tenían la forma pauciarticular; 9, la poliarticular y 6, la sistémica. RESULTADOS. Al final del tratamiento, 13 pacientes (65 por ciento) se evaluaron como respondedores. El número de articulaciones afectadas, los síntomas sistémicos y los valores de eritrosedimentación y del cuestionario de calidad se redujeron significativamente. Igualmente disminuyó el número de pacientes que continuó consumiendo esteroides, así como la dosis de éstos. El tratamiento fue bien tolerado, excepto en 2 pacientes. CONCLUSIONES. El INFγ disminuye la expresión de la quimiocina CCR-4 en los niños, pero no en los adultos con la enfermedad. Es posible concluir que esta citocina puede ser una alternativa terapéutica eficaz en pacientes con AIJ; para confirmarlo se necesitan estudios controlados más extensos(AU)

INTRODUCTION: The juvenile idiopathic arthritis (JIA) is a collagen entity characterized by chronic synovitis and extra-articulation symptoms appearing before the 16 years old. Gamma Interferon (gamma-INF) showed its effectiveness in a prior trial with resistant and intolerant patients to other available gamma-INF therapies, thus authors assessed its effectiveness and safety as a modifier drug of the course of this entity. METHODS: An open clinical, no-controlled trial was carried out administering gammaINF by intramuscular route in doses of 50 000 IU/kg (up to 1 x 10(6) IU) during two years. Trial included 20 patients with JIA: five had the pauciarticular type; nine had the polyarticular one and six had the systemic one. RESULTS: At treatment termination, 13 patients (65 percent) were assessed as respondents. Figure of involved joints, the systemic symptoms and the erythrosedimentation values, and the quality questionnaire significantly decreased, as well as the figure of patients to continue consuming steroids and its dosage. Treatment was well tolerated, except 2 patients. CONCLUSIONS: Gamma-INF decrease the expression of CCR-4 chemokine in children, but not in adults ones presenting this entity. We conclude that this cytokine may be an efficient therapeutical alternative in patients with JIA; for its confirmation it is necessary more extent controlled studies(AU)

Interferón gamma recombinante como alternativa terapéutica en niños con artritis idiopática juvenil / Recombinant gamma Interferon as a therapeutical alternative in children with juvenile idiopathic arthritis

INTRODUCCIÓN. La artritis idiopática juvenil (AIJ) es una enfermedad del colágeno caracterizada por sinovitis crónica y síntomas extraarticulares, de inicio antes de los 16 años de edad. El interferón gamma (INFγ) mostró eficacia en un ensayo anterior con pacientes resistentes o intolerantes a las otras terapias disponibles, por lo que se decidió evaluar su eficacia y seguridad como medicamento modificador de la evolución de esta enfermedad. MÉTODOS. Se realizó un ensayo clínico abierto, no controlado, en el que se administró INFγ por vía intramuscular en dosis de 50 000 UI/kg (hasta 1 x 10(6) UI) durante 2 años. En el ensayo se incluyeron 20 pacientes con AIJ: 5 tenían la forma pauciarticular; 9, la poliarticular y 6, la sistémica. RESULTADOS. Al final del tratamiento, 13 pacientes (65 por ciento) se evaluaron como respondedores. El número de articulaciones afectadas, los síntomas sistémicos y los valores de eritrosedimentación y del cuestionario de calidad se redujeron significativamente. Igualmente disminuyó el número de pacientes que continuó consumiendo esteroides, así como la dosis de éstos. El tratamiento fue bien tolerado, excepto en 2 pacientes. CONCLUSIONES. El INFγ disminuye la expresión de la quimiocina CCR-4 en los niños, pero no en los adultos con la enfermedad. Es posible concluir que esta citocina puede ser una alternativa terapéutica eficaz en pacientes con AIJ; para confirmarlo se necesitan estudios controlados más extensos

INTRODUCTION: The juvenile idiopathic arthritis (JIA) is a collagen entity characterized by chronic synovitis and extra-articulation symptoms appearing before the 16 years old. Gamma Interferon (gamma-INF) showed its effectiveness in a prior trial with resistant and intolerant patients to other available gamma-INF therapies, thus authors assessed its effectiveness and safety as a modifier drug of the course of this entity. METHODS: An open clinical, no-controlled trial was carried out administering gammaINF by intramuscular route in doses of 50 000 IU/kg (up to 1 x 10(6) IU) during two years. Trial included 20 patients with JIA: five had the pauciarticular type; nine had the polyarticular one and six had the systemic one. RESULTS: At treatment termination, 13 patients (65 percent) were assessed as respondents. Figure of involved joints, the systemic symptoms and the erythrosedimentation values, and the quality questionnaire significantly decreased, as well as the figure of patients to continue consuming steroids and its dosage. Treatment was well tolerated, except 2 patients. CONCLUSIONS: Gamma-INF decrease the expression of CCR-4 chemokine in children, but not in adults ones presenting this entity. We conclude that this cytokine may be an efficient therapeutical alternative in patients with JIA; for its confirmation it is necessary more extent controlled studies

Is complementary and alternative healthcare use associated with better outcomes in children with juvenile idiopathic arthritis?

OBJECTIVE: The objectives of this study were (1) to examine the association between the use of complementary and alternative healthcare (CAHC) and subsequent health outcomes; and (2) to explore the association between CAHC use and adherence to conventional treatments in children with juvenile idiopathic arthritis (JIA). METHODS: A cohort of children with JIA (n = 182, mean age 10 yrs) who attended outpatient clinics were followed for one year. We evaluated the use of CAHC, health-related quality of life (HRQOL), global health, physical functioning, pain, and disease severity at 3-month intervals. We also evaluated perceived adherence to treatments. General estimating equations were performed to determine the association between use of CAHC and subsequent outcomes while controlling for possible confounders. RESULTS: CAHC was used by 36.4% of participants over the 12-month period. Use of CAHC was associated with subsequent lower global health and physical functioning despite higher adherence to prescribed medications as assessed by the rheumatologist (p < 0.05). Use of CAHC was not associated with subsequent improved HRQOL or decreased pain or disease severity. CONCLUSION: Children with JIA who use CAHC do not have improved outcomes, at least over the relatively short term. Nevertheless, they seem to be more adherent to conventional treatment according to the rheumatologist.

Damage-associated molecular patterns--emerging targets for biologic therapy of childhood arthritides.

Juvenile idiopathic arthritis (JIA) is a group of chronic childhood arthritides of unknown origin. Although the use of glucocorticoids and immunosuppressants brought a substantial improvement in treatment, the present therapeutic regime could not be considered satisfactory. As inflammation seems to be an essential part of pathogenesis of JIA, efforts have been made to develop pharmaceutical means to mitigate the innate immune system. Emerging targets for treatment are alarmins, a family of multifunctional intracellular proteins with strong pro-inflammatory activity. In the context of JIA, particularly interesting are high mobility group box 1 (HMGB-1) and three members of the S100 family: S100A8, S100A9, and S100A12. No definite conclusion can be made at the time, but both animal models and clinical studies support the concept of alarmins as possible key mediators of JIA. Therefore, pharmacological interference with alarmin pathways could turn out to be an excellent strategy for long-term management of JIA. Several options have been tested and they either inhibit the release of alarmins or sequester the already secreted ones. Although still very few in number, therapeutic experiments on mice are quite optimistic. Thus, it was the purpose of the present review to give an overview of the present knowledge on the topic and to bring this exciting new therapeutic possibility to the focus of rheumatologists.