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Pediatric Rheumatology Online Journal Dec 2021This study aimed to perform an immunoprofiling of systemic juvenile idiopathic arthritis (sJIA) in order to define biomarkers of clinical use as well as reveal new...
BACKGROUND
This study aimed to perform an immunoprofiling of systemic juvenile idiopathic arthritis (sJIA) in order to define biomarkers of clinical use as well as reveal new immune mechanisms.
METHODS
Immunoprofiling of plasma samples from a clinically well-described cohort consisting of 21 sJIA patients as well as 60 age and sex matched healthy controls, was performed by a highly sensitive proteomic immunoassay. Based on the biomarkers being significantly up- or down-regulated in cross-sectional and paired analysis, related canonical pathways and cellular functions were explored by Ingenuity Pathway Analysis (IPA).
RESULTS
The well-studied sJIA biomarkers, IL6, IL18 and S100A12, were confirmed to be increased during active sJIA as compared to healthy controls. IL18 was the only factor found to be increased during inactive sJIA as compared to healthy controls. Novel factors, including CASP8, CCL23, CD6, CXCL1, CXCL11, CXCL5, EIF4EBP1, KITLG, MMP1, OSM, SIRT2, SULT1A1 and TNFSF11, were found to be differentially expressed in active and/or inactive sJIA and healthy controls. No significant pathway activation could be predicted based on the limited factor input to the IPA. High Mobility Group Box 1 (HMGB1), a damage associated molecular pattern being involved in a series of inflammatory diseases, was determined to be higher in active sJIA than inactive sJIA.
CONCLUSIONS
We could identify a novel set of biomarkers distinguishing active sJIA from inactive sJIA or healthy controls. Our findings enable a better understanding of the immune mechanisms active in sJIA and aid the development of future diagnostic and therapeutic strategies.
Topics: Adolescent; Arthritis, Juvenile; Biomarkers; Child; Child, Preschool; Cross-Sectional Studies; Female; Humans; Male; Proteomics
PubMed: 34963488
DOI: 10.1186/s12969-021-00660-9 -
Pediatric Rheumatology Online Journal Mar 2024Biomarkers may be useful in monitoring disease activity in juvenile idiopathic arthritis (JIA). With new treatment options and treatment goals in JIA, there is an urgent...
BACKGROUND
Biomarkers may be useful in monitoring disease activity in juvenile idiopathic arthritis (JIA). With new treatment options and treatment goals in JIA, there is an urgent need for more sensitive and responsive biomarkers.
OBJECTIVE
We aimed to investigate the patterns of 92 inflammation-related biomarkers in serum and saliva in a group of Norwegian children and adolescents with JIA and controls and in active and inactive JIA. In addition, we explored whether treatment with tumor necrosis factor inhibitors (TNFi) affected the biomarker levels.
METHODS
This explorative, cross-sectional study comprised a subset of children and adolescents with non-systemic JIA and matched controls from the Norwegian juvenile idiopathic arthritis study (NorJIA Study). The JIA group included individuals with clinically active or inactive JIA. Serum and unstimulated saliva were analyzed using a multiplex assay of 92 inflammation-related biomarkers. Welch's t-test and Mann-Whitney U-test were used to analyze the differences in biomarker levels between JIA and controls and between active and inactive disease.
RESULTS
We included 42 participants with JIA and 30 controls, predominantly females, with a median age of 14 years. Of the 92 biomarkers, 87 were detected in serum, 73 in saliva, and 71 in both biofluids. A pronounced difference between serum and salivary biomarker patterns was found. Most biomarkers had higher levels in serum and lower levels in saliva in JIA versus controls, and in active versus inactive disease. In serum, TNF and S100A12 levels were notably higher in JIA and active disease. The TNF increase was less pronounced when excluding TNFi-treated individuals. In saliva, several biomarkers from the chemokine family were distinctly lower in the JIA group, and levels were even lower in active disease.
CONCLUSION
In this explorative study, the serum and salivary biomarker patterns differed markedly, suggesting that saliva may not be a suitable substitute for serum when assessing systemic inflammation in JIA. Increased TNF levels in serum may not be a reliable biomarker for inflammatory activity in TNFi-treated children and adolescents with JIA. The lower levels of chemokines in saliva in JIA compared to controls and in active compared to inactive disease, warrant further investigation.
Topics: Child; Adolescent; Female; Humans; Male; Arthritis, Juvenile; Cross-Sectional Studies; Saliva; Inflammation; Biomarkers
PubMed: 38461338
DOI: 10.1186/s12969-024-00972-6 -
Pediatric Rheumatology Online Journal Aug 2021Juvenile idiopathic arthritis (JIA), is the most common pediatric rheumatologic disorder with unknown etiology. Currently, no population-based data are available...
BACKGROUND
Juvenile idiopathic arthritis (JIA), is the most common pediatric rheumatologic disorder with unknown etiology. Currently, no population-based data are available regarding the distribution of categories and frequency of uveitis in patients with JIA in Turkey. The purpose of this study was to evaluate the frequency of JIA-associated uveitis (JIAU) and distribution of JIA categories in a Turkish JIA cohort.
METHODS
This was a retrospective study of 500 randomized patients in four pediatric rheumatology clinics in Turkey.
RESULTS
Oligoarticular JIA (oJIA) was the most common JIA disease category in this study cohort (38.8%). The frequencies of the other categories were as follows: enthesitis-related arthritis (ERA), 23.2%; rheumatoid factor (RF)-negative polyarthritis, 15.6%; systemic arthritis, 12.2%; juvenile psoriatic arthritis, 5.2%; undifferentiated arthritis, 2.8%; and RF-positive polyarthritis, 2.2%. JIA-associated uveitis was observed in 6.8% of patients at a mean (Standard Deviation, SD) age of 9.1 (3.8) years over a mean JIA disease duration of 4 (1.9) years. Uveitis developed after joint disease, with a mean (SD) duration of 1.8 (1.9) years. Patients with oJIA had the highest rate of uveitis (12.9%) followed by patients with ERA (5.2%) and polyarticular RF-negative disease (3.8%). Compared with persistent oJIA, the extended oJIA category had a > 3-fold higher risk of uveitis (11.3% vs 27.7%; odds ratio, 3.38 [95% Confidence Interval, 1.09-10.4]). The most frequently administered drug after development of uveitis was tumor necrosis factor-alpha inhibitors (38.2%). Five patients (14.7%) had uveitis-related complications that required surgical intervention.
CONCLUSIONS
Turkish pediatric patients with JIA experience a lower frequency of oJIA and higher frequency of ERA than their white European counterparts; the occurrence of uveitis is also somewhat lower than expected. Geographic and ethnic factors may affect these differences and need further investigation.
Topics: Adolescent; Arthritis, Juvenile; Child; Cohort Studies; Female; HLA-B27 Antigen; Humans; Male; Patient Acuity; Patient Care Management; Prevalence; Random Allocation; Retrospective Studies; Risk Assessment; Severity of Illness Index; Tumor Necrosis Factor Inhibitors; Turkey; Uveitis
PubMed: 34425847
DOI: 10.1186/s12969-021-00613-2 -
Pediatric Rheumatology Online Journal Jul 2023Juvenile idiopathic arthritis (JIA) is a common pediatric rheumatic condition and is associated with symptoms such as joint pain that can negatively impact...
BACKGROUND
Juvenile idiopathic arthritis (JIA) is a common pediatric rheumatic condition and is associated with symptoms such as joint pain that can negatively impact health-related quality of life. To effectively manage pain in JIA, young people, their families, and health care providers (HCPs) should be supported to discuss pain management options and make a shared decision. However, pain is often under-recognized, and pain management discussions are not optimal. No studies have explored decision-making needs for pain management in JIA using a shared decision making (SDM) model. We sought to explore families' decision-making needs with respect to pain management among young people with JIA, parents/caregivers, and HCPs.
METHODS
We conducted semi-structured virtual or face-to-face individual interviews with young people with JIA 8-18 years of age, parents/caregivers and HCPs using a qualitative descriptive study design. We recruited participants online across Canada and the United States, from a hospital and from a quality improvement network. We used interview guides based on the Ottawa Decision Support Framework to assess decision-making needs. We audiotaped, transcribed verbatim and analyzed interviews using thematic analysis.
RESULTS
A total of 12 young people (n = 6 children and n = 6 adolescents), 13 parents/caregivers and 11 HCPs participated in interviews. Pediatric HCPs were comprised of rheumatologists (n = 4), physical therapists (n = 3), rheumatology nurses (n = 2) and occupational therapists (n = 2). The following themes were identified: (1) need to assess pain in an accurate manner; (2) need to address pain in pediatric rheumatology consultations; (3) need for information on pain management options, especially nonpharmacological approaches; (4) importance of effectiveness, safety and ease of use of treatments; (5) need to discuss young people/families' values and preferences for pain management options; and the (6) need for decision support. Themes were similar for young people, parents/caregivers and HCPs, although their respective importance varied.
CONCLUSIONS
Findings suggest a need for evidence-based information and communication about pain management options, which would be addressed by decision support interventions and HCP training in pain and SDM. Work is underway to develop such interventions and implement them into practice to improve pain management in JIA and in turn lead to better health outcomes.
Topics: Adolescent; Child; Humans; Arthritis, Juvenile; Pain; Pain Management; Qualitative Research; Quality of Life; Decision Making, Shared
PubMed: 37491246
DOI: 10.1186/s12969-023-00849-0 -
Pediatric Rheumatology Online Journal Aug 2022Juvenile Idiopathic Arthritis (JIA) is a childhood-rheumatic disease with pain as a major early complaint, and in 10-17% pain remains a major symptom. Very few data...
OBJECTIVE
Juvenile Idiopathic Arthritis (JIA) is a childhood-rheumatic disease with pain as a major early complaint, and in 10-17% pain remains a major symptom. Very few data exist on sensory threshold changes at the knee in JIA, a location in which inflammation often manifests. We determined whether JIA is associated with sensory threshold changes at the knee by using Quantitative Sensory Testing (QST) and established reference values at the knee of children.
METHODS
Sixteen patients with JIA aged 9-18 years with one affected knee and a patient-reported pain by Visual Analog Scale (VAS) > 10 on a 0-100 scale, and 16 healthy controls completed the study and were included for the analysis. QST was assessed in compliance with the German Research Network on Neuropathic Pain (DFNS) standard. Disease severity was determined using Juvenile Disease Activity Score (JADAS. Perceived pain was assessed with a visual analogue scale(0-100). Feasibility of QST was tested in patients aged 6-9.
RESULTS
Under the age of 9, QST testing showed not to be feasible in 3 out of 5 JIA patients. Patients with JIA aged 9 and older reported an average VAS pain score of 54.3. QST identified a significant reduction in pressure pain threshold (PPT) and increase in cold detection threshold (CDT) compared to healthy controls. PPT is reduced in both the affected and the unaffected knee, CDT is reduced in the unaffected knee, not the affected knee.
CONCLUSION
In a Dutch cohort of Patients with JIA, QST is only feasible from 9 years and up. Also, sensory threshold changes at the knee are restricted to pressure pain and cold detection thresholds in Patients with JIA.
PERSPECTIVE
This article shows that in a Dutch population, the extensive QST protocol is only feasible in the age group from 9 years and older, and a reduced set of QST tests containing at least pressure pain thresholds and cold detection thresholds could prove to be better suited to the pediatric setting with arthritis.
Topics: Arthritis, Juvenile; Child; Feasibility Studies; Humans; Neuralgia; Pain Measurement; Pain Threshold; Sensory Thresholds
PubMed: 35945540
DOI: 10.1186/s12969-022-00715-5 -
Expert Review of Clinical Immunology Jan 2021
Topics: Arthritis, Juvenile; Humans; Machine Learning
PubMed: 33475006
DOI: 10.1080/1744666X.2020.1850268 -
The Medical Journal of Malaysia Jul 2022Juvenile idiopathic arthritis (JIA) is the most common rheumatic condition that develops during child age and adolescence. Unbalanced production of proinflammatory...
INTRODUCTION
Juvenile idiopathic arthritis (JIA) is the most common rheumatic condition that develops during child age and adolescence. Unbalanced production of proinflammatory cytokines is suggested to participate in the etio-pathogenesis of JIA, so the objective of this study is to evaluate the role of interleukins (IL), IL-37 and IL-38, in patients with JIA.
MATERIALS AND METHODS
Sixty patients with JIA (19 males, 41 females) and 90 healthy controls (35 males, 55 females) were included in this study. Participants were assessed using the juvenile arthritis disease activity score-27 and underwent laboratory tests, including measurements for C-reactive protein, rheumatoid factor, and IL-37 and IL-38.
RESULTS
Mean ages of JIA patients and controls were 10.37±4.21 years and 11.13±3.84 years, respectively. Compared to controls, serum IL-37 levels were increased in patients with JIA (117.98±209.282ng/ml vs. 37.87±24.496ng/ml; p<0.01), whereas serum IL-38 titres were diminished in individuals with JIA (106.2±95.781ng/ml vs. 182.24±108.428 ng/ml; p<0.01).
CONCLUSION
This study provides a further layer of evidence for the role played by IL-37 in JIA and creates new questions about the potential role of IL-38 in this condition.
Topics: Adolescent; Arthritis, Juvenile; Biomarkers; C-Reactive Protein; Child; Cytokines; Female; Humans; Interleukin-1; Interleukins; Male
PubMed: 35902929
DOI: No ID Found -
Reumatologia Clinica 2015Uveitis occurs within the first year of arthritis onset in 73% of patients with juvenile idiopathic arthritis (JIA) considered at risk. The intraocular inflammation is... (Review)
Review
Uveitis occurs within the first year of arthritis onset in 73% of patients with juvenile idiopathic arthritis (JIA) considered at risk. The intraocular inflammation is characterized by an insidious onset and a silent and chronic clinical course capable of producing significant visual loss due to complications such as: cataract formation, secondary glaucoma, maculopathy and optic neuropathy. The absence of initial signs and symptoms, along with a deficient ophthalmic monitoring produce a delay in diagnosis with serious consequences. It has been estimated that 47% of JIA patients at risk for developing uveitis are legally blind (20/200 or worse) at least in one eye at the time of their first visit to the ophthalmologist. To reduce ocular complications and improve their visual outcome, it is necessary that rheumatologists refer all patients recently diagnosed (within the first month) with JIA for an ophthalmic evaluation, and maintain periodical follow-up visits based on classification and risk category of the disease.
Topics: Aftercare; Arthritis, Juvenile; Diagnostic Techniques, Ophthalmological; Disease Progression; Humans; Risk Factors; Uveitis
PubMed: 25488285
DOI: 10.1016/j.reuma.2014.08.003 -
Pediatric Rheumatology Online Journal Apr 2023To develop and evaluate German versions of the Parent Adherence Report Questionnaire (PARQ) and Child Adherence Report Questionnaire (CARQ) and to evaluate adherence in...
OBJECTIVES
To develop and evaluate German versions of the Parent Adherence Report Questionnaire (PARQ) and Child Adherence Report Questionnaire (CARQ) and to evaluate adherence in patients with juvenile idiopathic arthritis (JIA).
METHODS
The PARQ and CARQ were translated into German, cross-culturally adapted and administered to patients (age ≥ 8 years) and their parents enrolled in the Inception Cohort Study of newly diagnosed JIA patients (ICON). The psychometric issues were explored by analyzing their test-retest reliability and construct validity.
RESULTS
Four hundred eighty-one parents and their children with JIA (n = 465) completed the PARQ and CARQ at the 4-year follow-up. Mean age and disease duration of patients were 10.1 ± 3.7 and 4.7 ± 0.8 years, respectively. The rate of missing values for PARQ/CARQ was generally satisfactory, test-retesting showed sufficient reliability. PARQ/CARQ mean child ability total scores (0-100, 100 = best) for medication were 73.1 ± 23.3/76.5 ± 24.2, for exercise: 85.6 ± 16.5/90.3 ± 15.0, for splints: 72.9 ± 24.2/82.9 ± 16.5. Construct validity was supported by PARQ and CARQ scores for medications, exercise and splints showing a fair to good correlation with the Global Adherence Assessment (GAA) and selected PedsQL scales. Adolescents showed poorer adherence than children. About one third of the parents and children reported medication errors. Perceived helpfulness was highest for medication, and adverse effects were reported the greatest barrier to treatment adherence.
CONCLUSIONS
The German versions of the PARQ and CARQ appear to have a good reliability and sufficient construct validity. These questionnaires are valuable tools for measuring treatment adherence, identifying potential barriers and evaluating helpfulness of treatments in patients with JIA.
Topics: Child; Adolescent; Humans; Arthritis, Juvenile; Quality of Life; Cohort Studies; Reproducibility of Results; Exercise; Parents; Psychometrics; Translating; Disability Evaluation; Health Status; Case-Control Studies
PubMed: 37046303
DOI: 10.1186/s12969-023-00811-0 -
BMC Pediatrics Mar 2021Phenylketonuria (PKU) is a genetic metabolic disorder in which patients have no ability to convert phenylalanine to tyrosine. Several autoimmune diseases have been...
BACKGROUND
Phenylketonuria (PKU) is a genetic metabolic disorder in which patients have no ability to convert phenylalanine to tyrosine. Several autoimmune diseases have been reported to combine with PKU, co-existent of PKU and Juvenile Idiopathic Arthritis (JIA) has not been presented.
CASE PRESENTATION
The girl was diagnosed with PKU at the age of 1 month confirmed by molecular data. At the age of 3.5 years, she presented with pain and swelling of her right ankle, right knee, and right hip joint. After a serial of examinations, she was diagnosed with JIA and treated with a nonsteroidal anti-inflammatory drug.
CONCLUSIONS
We report a rare case of a 4-year-old girl with PKU and JIA, which supports a possible interaction between PKU and JIA. Long-term metabolic disturbance may increase the susceptibility to JIA. Further chronic inflammation could alter the metabolism of tryptophan and tyrosine to increase blood Phe concentration. In addition, corticosteroid and methotrexate therapy for JIA may increase blood Phe concentration.
Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Juvenile; Child, Preschool; Female; Humans; Phenylalanine; Phenylketonurias
PubMed: 33722205
DOI: 10.1186/s12887-021-02602-6