Juvenile idiopathic arthritis is a common rheumatic disease that presents as chronic childhood arthritis. JIA is considered a multifactorial disease that may result from diverse genetic and ...environmental risk factors. A minority of the population-attributable risk of JIA is estimated to be due to familial factors. Thus, non-genetic or environmental factors likely account for a majority of the risk of developing JIA. Yet, while substantial data have linked environmental factors to the development of rheumatoid arthritis, similar evidence regarding JIA is sparse. This narrative review provides updates on recent literature about environmental factors that might influence the risk of developing JIA, including studies about potentially beneficial and harmful influences as well as factors with unclear effects. Keywords: environmental exposure, risk factors, juvenile arthritis, antibiotics, breast feeding, cesarean section
Systemic juvenile idiopathic arthritis (SJIA) is a disease marked with arthritis and several features of systemic inflammation including fevers, rashes, hepatosplenomegaly, lymphadenopathy, and ...serositis. The presentation can be variable and arthritis can be a later feature. Macrophage activation syndrome can be a life-threatening complication of this illness and requires early recognition and prompt therapy. Advancements in understanding the biology of SJIA have led to the development of cytokine-targeted therapies, mainly interleukin-1 (IL-1) and IL-6 inhibitors that have significantly improved outcomes. In this review, we provide an update on the advances in the understanding of SJIA biology and also the therapeutic options.
To investigate the characteristics and risk factors of a novel parenchymal lung disease (LD), increasingly detected in systemic juvenile idiopathic arthritis (sJIA).
In a multicentre retrospective ...study, 61 cases were investigated using physician-reported clinical information and centralised analyses of radiological, pathological and genetic data.
LD was associated with distinctive features, including acute erythematous clubbing and a high frequency of anaphylactic reactions to the interleukin (IL)-6 inhibitor, tocilizumab. Serum ferritin elevation and/or significant lymphopaenia preceded LD detection. The most prevalent chest CT pattern was septal thickening, involving the periphery of multiple lobes ± ground-glass opacities. The predominant pathology (23 of 36) was pulmonary alveolar proteinosis and/or endogenous lipoid pneumonia (PAP/ELP), with atypical features including regional involvement and concomitant vascular changes. Apparent severe delayed drug hypersensitivity occurred in some cases. The 5-year survival was 42%. Whole exome sequencing (20 of 61) did not identify a novel monogenic defect or likely causal PAP-related or macrophage activation syndrome (MAS)-related mutations. Trisomy 21 and young sJIA onset increased LD risk. Exposure to IL-1 and IL-6 inhibitors (46 of 61) was associated with multiple LD features. By several indicators, severity of sJIA was comparable in drug-exposed subjects and published sJIA cohorts. MAS at sJIA onset was increased in the drug-exposed, but was not associated with LD features.
A rare, life-threatening lung disease in sJIA is defined by a constellation of unusual clinical characteristics. The pathology, a PAP/ELP variant, suggests macrophage dysfunction. Inhibitor exposure may promote LD, independent of sJIA severity, in a small subset of treated patients. Treatment/prevention strategies are needed.
Abstract
Objective
We aimed to investigate the potential of growth differentiation factor 15 (GDF-15) as a novel biomarker for disease activity in JDM.
Methods
We recruited children with juvenile ...myositis including JDM (n = 77), PM (n = 6) and healthy controls (n = 22). GDF-15 levels in plasma were measured using ELISA. Statistical analyses were performed using non-parametric tests.
Results
Levels of GDF-15 were significantly elevated in JDM compared with healthy controls (P < 0.001). GDF-15 levels exhibited strong positive correlations with DASs, including the DAS total score, DAS skin score, DAS muscle score and Childhood Myositis Assessment Scale. Additionally, GDF-15 levels could differentiate between active disease and remission based on the Physician Global Assessment of muscle score. Positive correlations were observed between levels of GDF-15 and creatine kinase, neopterin and nailfold end row loops, indicating the potential involvement of GDF-15 in muscle damage, immune activation and vascular pathology. Receiver operating characteristics curve analysis showed GDF-15 to be more effective in assessing disease activity in JDM than creatine kinase area under the curve (AUC) 0.77, P = 0.001 and AUC 0.6369, P = 0.0738, respectively.
Conclusion
GDF-15 may serve as a valuable biomarker for assessing disease activity in JDM. It exhibits better sensitivity and specificity than creatine kinase and the levels correlate with various DASs and functional measures. GDF-15 may provide valuable information for treatment decision making and monitoring disease progression in JDM.
Objective
To provide updated guidelines for pharmacologic management of juvenile idiopathic arthritis (JIA), focusing on treatment of oligoarthritis, temporomandibular joint (TMJ) arthritis, and ...systemic JIA with and without macrophage activation syndrome. Recommendations regarding tapering and discontinuing treatment in inactive systemic JIA are also provided.
Methods
We developed clinically relevant Patient/Population, Intervention, Comparison, and Outcomes questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the quality of evidence (high, moderate, low, or very low). A Voting Panel including clinicians and patients/caregivers achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations.
Results
Similar to those published in 2019, these JIA recommendations are based on clinical phenotypes of JIA, rather than a specific classification schema. This guideline provides recommendations for initial and subsequent treatment of JIA with oligoarthritis, TMJ arthritis, and systemic JIA as well as for tapering and discontinuing treatment in subjects with inactive systemic JIA. Other aspects of disease management, including factors that influence treatment choice and medication tapering, are discussed. Evidence for all recommendations was graded as low or very low in quality. For that reason, more than half of the recommendations are conditional.
Conclusion
This clinical practice guideline complements the 2019 American College of Rheumatology JIA and uveitis guidelines, which addressed polyarthritis, sacroiliitis, enthesitis, and uveitis. It serves as a tool to support clinicians, patients, and caregivers in decision‐making. The recommendations take into consideration the severity of both articular and nonarticular manifestations as well as patient quality of life. Although evidence is generally low quality and many recommendations are conditional, the inclusion of caregivers and patients in the decision‐making process strengthens the relevance and applicability of the guideline. It is important to remember that these are recommendations. Clinical decisions, as always, should be made by the treating clinician and patient/caregiver.
Juvenile idiopathic arthritis is a common rheumatic disease that presents as chronic childhood arthritis. JIA is considered a multifactorial disease that may result from diverse genetic and ...environmental risk factors. A minority of the population-attributable risk of JIA is estimated to be due to familial factors. Thus, non-genetic or environmental factors likely account for a majority of the risk of developing JIA. Yet, while substantial data have linked environmental factors to the development of rheumatoid arthritis, similar evidence regarding JIA is sparse. This narrative review provides updates on recent literature about environmental factors that might influence the risk of developing JIA, including studies about potentially beneficial and harmful influences as well as factors with unclear effects.
Objective
There is no standardized approach to the initial treatment of polyarticular juvenile idiopathic arthritis (JIA) among pediatric rheumatologists. Understanding the comparative effectiveness ...of the diverse therapeutic options available will result in better health outcomes for polyarticular JIA. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed consensus treatment plans (CTPs) for use in clinical practice to facilitate such studies.
Methods
A case‐based survey was administered to CARRA members to identify the common treatment approaches for new‐onset polyarticular JIA. Two face‐to‐face consensus conferences employed modified nominal group technique to identify treatment strategies, operational case definition, end points, and data elements to be collected. A core workgroup reviewed the relevant literature, refined plans, and developed medication dosing and monitoring recommendations.
Results
The initial case‐based survey identified significant variability among treatment approaches for new‐onset polyarticular JIA. We developed 3 CTPs based on treatment strategies for the first 12 months of therapy, as well as case definitions and clinical and laboratory monitoring schedules. The CTPs include a step‐up plan (nonbiologic disease‐modifying antirheumatic drug DMARD followed by a biologic DMARD), an early combination plan (nonbiologic and biologic DMARD combined within a month of treatment initiation), and a biologic only plan. This approach was approved by 96% of the CARRA JIA Research Committee members attending the 2013 CARRA face‐to‐face meeting.
Conclusion
Three standardized CTPs were developed for new‐onset polyarticular JIA. Coupled with data collection at defined intervals, use of these CTPs will enable the study of their comparative effectiveness in an observational setting to optimize initial management of polyarticular JIA.
PDF
