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Postepy Higieny I Medycyny... Jul 2016The inflammatory response by secretion of cytokines and other mediators is postulated as one of the most significant factors in the pathophysiology of juvenile... (Review)
Review
The inflammatory response by secretion of cytokines and other mediators is postulated as one of the most significant factors in the pathophysiology of juvenile idiopathic arthritis (JIA). The effect of macrophage action depends on the type of their activation. Classically activated macrophages (M1) are responsible for release of molecules crucial for joint inflammation. Alternatively activated macrophages (M2) may recognize self antigens by scavenger receptors and induce the immunological reaction leading to autoimmune diseases such as JIA. Molecules essential for JIA pathophysiology include: TNF-α, the production of which precedes synovial inflammation in rheumatoid arthritis; IL-1 as a key mediator of synovial damage; chemotactic factors for macrophages IL-8 and MCP-1; IL6, the level of which correlates with the radiological joint damage; MIF, promoting the secretion of TNF-α and IL-6; CCL20 and HIF, significant for the hypoxic synovial environment in JIA; GM-CSF, stimulating the production of macrophages; and IL-18, crucial for NK cell functions. Recognition of the role of macrophages creates the potential for a new therapeutic approach.
Topics: Arthritis, Juvenile; Autoimmunity; Cytokines; Humans; Macrophage Activation; Macrophages
PubMed: 27383571
DOI: 10.5604/17322693.1208887 -
Archives of Disease in Childhood Sep 2015
Topics: Arthritis, Juvenile; Female; Humans; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 26199406
DOI: 10.1136/archdischild-2015-308607 -
EBioMedicine Jul 2023The etiology of juvenile idiopathic arthritis (JIA) is poorly understood. This study investigated genetic and environmental factors and infant gut microbiota in a...
BACKGROUND
The etiology of juvenile idiopathic arthritis (JIA) is poorly understood. This study investigated genetic and environmental factors and infant gut microbiota in a prospective birth cohort to assess disease risk.
METHODS
Data was collected from the All Babies in Southeast Sweden (ABIS) population-based cohort (n = 17,055), 111 of whom later acquired JIA (ABIS). Stool samples were collected at one year of age for 10.4%. To determine disease association, 16S rRNA gene sequences were analyzed, with and without confound adjustment. Genetic and environmental risks were assessed.
FINDINGS
ABIS had higher abundance of Acidaminococcales, Prevotella 9, and Veillonella parvula and lower abundance of Coprococcus, Subdoligranulum, Phascolarctobacterium, Dialister spp., Bifidobacterium breve, Fusicatenibacter saccharivorans, Roseburia intestinalis, and Akkermansia muciniphila (q's < 0.05). Parabacteroides distasonis greatly increased the odds of later contracting JIA (OR = 6.7; 1.81-24.84, p = 0.0045). Shorter breastfeeding duration and increased antibiotic exposure compounded risk in a dose-dependent manner, especially in those with genetic predisposition.
INTERPRETATION
Microbial dysregulation in infancy may trigger or accelerate JIA development. Environmental risk factors have a stronger impact on genetically predisposed children. This study is the first to implicate microbial dysregulation in JIA at such an early age, with many bacterial taxa associated with risk factors. These findings provide opportunities for intervention or early screening and offer new insights into JIA pathogenesis.
FUNDING
Barndiabetesfonden; Swedish Council for Working Life and Social Research; Swedish Research Council; Östgöta Brandstodsbolag; Medical Research Council of Southeast Sweden; JDRF-Wallenberg Foundation; Linköping.
Topics: Child; Humans; Infant; Arthritis, Juvenile; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Prospective Studies; Genetic Predisposition to Disease
PubMed: 37329576
DOI: 10.1016/j.ebiom.2023.104654 -
Journal of Pediatric Psychology Oct 2019Given the high levels of pain and low rates of treatment adherence in children with juvenile idiopathic arthritis (JIA) and their families, this study sought to examine...
OBJECTIVE
Given the high levels of pain and low rates of treatment adherence in children with juvenile idiopathic arthritis (JIA) and their families, this study sought to examine the relationship between parent pain cognitions (i.e., pain catastrophizing, fear of pain) and treatment adherence, and how barriers to treatment (e.g., forgetting treatments, children resisting injections) may be implicated in this relationship.
METHODS
Parents of children under 18 years of age who have been diagnosed with JIA were recruited to complete an online survey. In total, 221 parents (93% mothers) of children aged 2-17 years (M = 11.10, SD = 4.25) took part, completing questions regarding their pain cognitions, perceived barriers to treatment, and their child's arthritis treatment adherence ability.
RESULTS
Hierarchical regressions demonstrated that both pain cognitions (i.e., pain catastrophizing and fear of pain) were related to a decrease in parent-reported treatment adherence, however, pain catastrophizing was no longer significant when fear of pain was added to the model. The presence of treatment barriers partially mediated the relationship between fear of pain and treatment adherence, above and beyond the alternate model proposed.
CONCLUSION
These results suggest that parent pain catastrophizing and fears of pain are related to a greater difficulty following treatment plans, possibly in part because of barriers parents experience that preclude adherence. Given these findings, the identification and management of parent pain cognitions is critical to improving treatment adherence and outcomes for children with JIA and their families.
Topics: Adolescent; Arthritis, Juvenile; Catastrophization; Child; Child, Preschool; Female; Humans; Male; Pain; Parents; Surveys and Questionnaires; Treatment Adherence and Compliance
PubMed: 31509198
DOI: 10.1093/jpepsy/jsz067 -
Medical Ultrasonography Aug 2018Musculoskeletal ultrasound (MSUS) has become almost indispensable in the rheumatology settings nowadays, allowing early diagnosis, careful guidance during procedures... (Review)
Review
Musculoskeletal ultrasound (MSUS) has become almost indispensable in the rheumatology settings nowadays, allowing early diagnosis, careful guidance during procedures such as joint injections and therapy monitoring. Nonetheless, the applicability of MSUS in pediatric population is still limited. Recently, a standardized MSUS examination procedure in pediatric patients with rheumatic diseases, definitions for synovitis and the sonographic features of joints in healthy children has been developed. Also, important data on age-related vascularization and ossification of joints in children have been published. Much work still needs to be done in the field. As juvenile idiopathic arthritis seems to be the most common use of MSUS in pediatric rheumatology, specific definitions and assessment techniques for enthesitis, tenosynovitis, bone and cartilage damage in children are very much expected. In this article, we will review briefly the current evidence-based knowledge regarding MSUS potential applications in the pediatric rheumatology clinical practice, along with an overview of the recent information about US appearance of musculoskeletal structures in healthy children.
Topics: Adolescent; Arthritis, Juvenile; Child; Forecasting; Humans; Male; Monitoring, Physiologic; Musculoskeletal Diseases; Pediatrics; Rheumatic Diseases; Rheumatology; Ultrasonography, Doppler
PubMed: 30167592
DOI: 10.11152/mu-1604 -
The Journal of Rheumatology Nov 2023To describe the efficacy and safety data of children with polyarticular-course juvenile idiopathic arthritis (pcJIA) treated with abatacept (ABA) + methotrexate (MTX) or...
OBJECTIVE
To describe the efficacy and safety data of children with polyarticular-course juvenile idiopathic arthritis (pcJIA) treated with abatacept (ABA) + methotrexate (MTX) or ABA monotherapy when prior MTX use was either ineffective or not tolerated.
METHODS
Posthoc analysis of 2 phase III trials of subcutaneous (SC) and intravenous (IV) ABA over 2 years in patients with pcJIA (aged 2-17 years). Patients were stratified by treatment with ABA + MTX or ABA monotherapy and further by prior biologic use. Efficacy outcomes included JIA-American College of Rheumatology (JIA-ACR) responses, Juvenile Arthritis Disease Activity Score in 27 joints using C-reactive protein (JADAS27-CRP), and safety. Descriptive pharmacokinetic analyses were also performed.
RESULTS
Efficacy responses (JIA-ACR and JADAS27-CRP) were similar between patients receiving ABA + MTX (n = 310) or ABA monotherapy (n = 99) and persisted over 2 years. Clinical response rates were similar in biologic-naïve patients and prior biologic users; this was independent of MTX use. Across both studies, ABA + MTX and ABA monotherapy displayed similar safety profiles. Pharmacokinetic results revealed similar minimum steady-state trough ABA concentrations between studies. Further, baseline MTX did not influence ABA clearance and was not a significant predictor of JIA-ACR responses.
CONCLUSION
ABA monotherapy (SC and IV) was effective and well tolerated in children with pcJIA when prior MTX use was ineffective or not tolerated. Treatment effects of ABA appear to be independent of MTX coadministration. Consequently, ABA monotherapy can be considered for those with prior biologic therapy if MTX use is inappropriate. (ClinicalTrials.gov: NCT01844518 and NCT00095173).
Topics: Child; Humans; Methotrexate; Abatacept; Arthritis, Juvenile; Antirheumatic Agents; Drug Therapy, Combination; Biological Products; Treatment Outcome
PubMed: 37453737
DOI: 10.3899/jrheum.2022-1320 -
The Journal of Rheumatology Mar 2017To examine the extent of polysomnographic (PSG) sleep disturbances [obstructive apnea hypopnea index (OAHI), number of wake bouts, arousals, periodic limb movements] and...
OBJECTIVE
To examine the extent of polysomnographic (PSG) sleep disturbances [obstructive apnea hypopnea index (OAHI), number of wake bouts, arousals, periodic limb movements] and the effect of OAHI on neurobehavioral performance in juvenile idiopathic arthritis (JIA) with obstructive sleep apnea (OSA), JIA without OSA, and controls without OSA, adjusting for intelligence quotient (IQ), pain, medications, daytime sleepiness, and wake bouts.
METHODS
Children 6-11 years, 68 with JIA and 67 controls, underwent 1 night of PSG and completed self-reported daytime sleepiness surveys, multiple sleep latency tests for physiological sleepiness, and neurobehavioral performance tests the next day.
RESULTS
Compared with JIA and controls without OSA, mean OAHI and arousals were significantly higher in JIA with OSA (p < 0.001, respectively). In comparison with JIA and controls without OSA, mean simple reaction time and sustained attention were significantly slower in JIA with OSA, adjusting for IQ, pain, any medication, daytime sleepiness, and wake bouts.
CONCLUSION
Elevated OAHI is suggestive of obstructive sleep apnea and a comorbidity in JIA that may predispose children with JIA to daytime sleepiness and impaired neurobehavioral performance.
Topics: Arthritis, Juvenile; Attention; Child; Female; Humans; Male; Neuropsychological Tests; Polysomnography; Reaction Time; Sleep; Sleep Wake Disorders
PubMed: 28089981
DOI: 10.3899/jrheum.160556 -
Anales de Pediatria Sep 2022(1) To describe the prevalence of IgA deficiency (IgAD), uveitis, coeliac disease (CD) and thyroid disorders in a multicentric cohort of patients diagnosed with JIA and,...
OBJECTIVES
(1) To describe the prevalence of IgA deficiency (IgAD), uveitis, coeliac disease (CD) and thyroid disorders in a multicentric cohort of patients diagnosed with JIA and, (2) to evaluate whether patients with JIA and IgAD present other autoimmune diseases more frequently than patients with normal serum levels of IgA.
METHODS
Retrospective chart review of a cohort of patients diagnosed with JIA followed at the paediatric rheumatology units of two hospitals in Madrid, Spain.
RESULTS
A total of 193 patients were included. Of them, 123 were females (64%). Median age at disease onset was 5.6 years (IQR 2.5-9.7) and the median time of follow-up was 5.1 years (IQR 2.2-8.1). The three most common ILAR categories were oligoarticular (53%), polyarticular RF negative (20%) and enthesitis related arthritis (10%). Serum IgA levels were available in 172/193 (89%); 25/172 (15%) had selective (<7mg/dl, n=8) or partial (7-69mg/dl, n=17) IgAD. All the patients had periodic eye exams. Eighteen children (9%) had anterior uveitis, 15/18 chronic and 3/18 acute. Serum anti transglutaminase IgA, or IgG in IgAD were obtained in 135/193 (70%). Four children (3%) were diagnosed with CD either by intestinal biopsy (n=3) or by the combination of characteristic clinical, serological and genetic features (n=1); two of them had IgAD (p=0.12; OR=6.4; 95% CI 0.9-47.6). Only 1/153 (0.7%) patient had hyperthyrotropinemia with positive anti-thyroid antibodies and required replacement therapy.
CONCLUSION
Patients with JIA frequently present autoimmune comorbidities. IgAD does not seem to increase their prevalence, with the possible exception of CD.
Topics: Arthritis, Juvenile; Celiac Disease; Child; Child, Preschool; Female; Humans; IgA Deficiency; Immunoglobulin A; Male; Retrospective Studies; Transglutaminases
PubMed: 35459637
DOI: 10.1016/j.anpede.2022.03.004 -
RMD Open May 2023Etanercept is commonly used to treat juvenile idiopathic arthritis, including juvenile psoriatic arthritis (JPsA); however, information on etanercept's safety and...
OBJECTIVE
Etanercept is commonly used to treat juvenile idiopathic arthritis, including juvenile psoriatic arthritis (JPsA); however, information on etanercept's safety and effectiveness in clinical practice is limited. We used data from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry to evaluate etanercept's safety and effectiveness in JPsA in clinical practice.
METHODS
We analysed safety and effectiveness data for paediatric patients enrolled in the CARRA Registry who had a JPsA diagnosis and had used etanercept. Safety was assessed by calculating rates of prespecified adverse events of special interest (AESIs) and serious adverse events (SAEs). Effectiveness was assessed by a variety of disease activity measures.
RESULTS
Overall, 226 patients had JPsA and received etanercept; 191 met criteria for safety analysis and 43 met criteria for effectiveness analysis. AESI and SAE incidence rates were low. There were five events: three uveitis, one new-onset neuropathy and one malignancy. Incidence rates were 0.55 (95% CI: 0.18, 1.69), 0.18 (95% CI: 0.03, 1.29) and 0.13 (95% CI: 0.02, 0.09) per 100 patient-years for uveitis, neuropathy and malignancy, respectively. Etanercept showed effectiveness for JPsA treatment; 7 of 15 (46.7%) had an American College of Rheumatology-Pediatric Response 90, 9 of 25 (36.0%) had a clinical Juvenile Arthritis Disease Activity Score 10-joint ≤1.1 and 14 of 27 (51.9%) had clinically inactive disease at the 6-month follow-up.
CONCLUSION
Data in the CARRA Registry showed that etanercept treatment was safe in treating children with JPsA, with low AESIs and SAEs. Etanercept was also effective, even when assessed in a small sample size.
Topics: Humans; Child; United States; Etanercept; Arthritis, Juvenile; Rheumatology; Registries
PubMed: 37230760
DOI: 10.1136/rmdopen-2022-002943 -
Arthritis Research & Therapy Jan 2018Significant progress has been made in the understanding of transitional care in rheumatology over the last few decades, yet universal implementation has not been...
Significant progress has been made in the understanding of transitional care in rheumatology over the last few decades, yet universal implementation has not been realised and unmet needs continue to be reported. Possible explanations for this include lack of evidence as to which model is most effective; lack of attention to the multiple dimensions, stakeholders and systems involved in health transitions; and lack of consideration of the developmental appropriateness of transition interventions and the services/organisations/systems where such interventions are delivered.Successful transition has major implications to both the young people with juvenile-onset rheumatic disease and their families. Future research in this area will need to reflect both the multidimensional (biopsychosocial) and the multisystemic (multiple systems and stakeholders across personal/social/family support networks and health/social care/education systems). Only then will we be able to determine which aspects of transition readiness and service components influence which dimension. It is therefore imperative we continue to research and develop this area, involving both paediatric and adult rheumatology clinicians and researchers, remembering to look beyond both the condition and our discipline. Neither should we forget to tap into the exciting potential associated with digital technology to ensure further advances in transitional care are brought about in and beyond rheumatology.
Topics: Adolescent; Adult; Age of Onset; Arthritis, Juvenile; Child; Humans; Rheumatic Diseases; Rheumatology; Transitional Care
PubMed: 29325599
DOI: 10.1186/s13075-017-1502-y