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European Review For Medical and... Oct 2017Juvenile rheumatoid arthritis (JRA), also known as juvenile idiopathic arthritis (JIA), is a rare autoimmune joint disorder of children. The concrete causes for the... (Review)
Review
OBJECTIVE
Juvenile rheumatoid arthritis (JRA), also known as juvenile idiopathic arthritis (JIA), is a rare autoimmune joint disorder of children. The concrete causes for the prevalence of the above pathological state are still unknown. In other words, it is an arthritis affecting mainly children and adolescents. Clinically, it has 3 different clinical subtypes. JRA patients are often noticed with some confirmed symptoms including coagulopathy, disseminated intravascular coagulation (DIC) with hepatosplenomegaly, fall in erythrocyte sedimentation rate and higher levels of liver enzymes leading to a life-threatening outcome. The above complications of JRA are recognized as a macrophage activation syndrome (MAS), which is similar to hemophagocytic lymphohistiocytosis (HLH). Pathogenesis of JRA manly involves deregulation of immunological processes with excessive and persistent activation of antigen presenting cells and T-lymphocytes. Further, abnormalities in the functioning of NK cells are often observed in JIA cases. Also, 40% of patients with these abnormalities are habitually associated with perforin gene mutations. Today, MAS remains a clinical and diagnostic challenge.
RESULTS
The diagnosis of MAS is mainly based on clinical grounds. However, laboratory evidence of macrophages in the bone marrow performing phagocytosis of variable hematopoietic cells also help in diagnosis. For confirmation of MAS, there must be present either of two clinical or laboratory criteria. Further, laboratory criteria often appear late and are unable to diagnose the complication right at the beginning stage. Important laboratory findings in macrophage activation syndrome associated with JIA include hypertriglyceridemia, anemia, low erythrocyte sedimentation rate, elevated alanine aminotransferase level, higher than normal bilirubin levels, presence of fibrin degradation products, high lactate dehydrogenase level, low sodium, low albumin, and hyperferritinemia.
CONCLUSIONS
MAS is a confirmed life threatening complication of patients with JIA. Further, an early diagnosis and treatment of MAS could be a life-saving mode for this syndrome.
Topics: Adolescent; Animals; Arthritis, Juvenile; Child; Humans; Macrophage Activation Syndrome
PubMed: 29077164
DOI: No ID Found -
Seminars in Arthritis and Rheumatism Aug 2021Pain is prevalent in juvenile idiopathic arthritis (JIA). Unknowns regarding the biological drivers of pain complicate therapeutic targeting. We employed neuroimaging...
INTRODUCTION
Pain is prevalent in juvenile idiopathic arthritis (JIA). Unknowns regarding the biological drivers of pain complicate therapeutic targeting. We employed neuroimaging to define pain-related neurobiological features altered in JIA.
METHODS
16 male and female JIA patients (12.7 ± 2.8 years of age) on active treatment were enrolled, together with age- and sex-matched controls. Patients were assessed using physical examination, clinical questionnaires, musculoskeletal MRI, and structural neuroimaging. In addition, functional magnetic resonance imaging (fMRI) data were collected during the resting-state, hand-motor task performance, and cold stimulation of the hand and knee.
RESULTS
Patients with and without pain and with and without inflammation (joint and systemic) were evaluated. Pain severity was associated with more physical stress and poorer cognitive function. Corrected for multiple comparisons, morphological analysis revealed decreased cortical thickness within the insula cortex and a negative correlation between caudate nucleus volume and pain severity. Functional neuroimaging findings suggested alteration within neurocircuitry structures regulating emotional pain processing (anterior insula) in addition to the default-mode and sensorimotor networks.
CONCLUSIONS
Patients with JIA may exhibit changes in neurobiological circuits related to pain. These preliminary findings suggest mechanisms by which pain could potentially become dissociated from detectable joint pathology and persist independently of inflammation or treatment status.
Topics: Arthritis, Juvenile; Female; Humans; Knee Joint; Magnetic Resonance Imaging; Male; Pain; Pain Measurement
PubMed: 34139523
DOI: 10.1016/j.semarthrit.2021.05.011 -
Pediatric Rheumatology Online Journal Jul 2016Juvenile idiopathic arthritis (JIA) is a clinically diverse and genetically complex autoimmune disease. Currently, there is very limited understanding of the potential... (Review)
Review
Juvenile idiopathic arthritis (JIA) is a clinically diverse and genetically complex autoimmune disease. Currently, there is very limited understanding of the potential underlying mechanisms that result in the range of phenotypes which constitute JIA.The elucidation of the functional relevance of genetic associations with phenotypic traits is a fundamental problem that hampers the translation of genetic observations to plausible medical interventions. Genome wide association studies, and subsequent fine-mapping studies in JIA patients, have identified many genetic variants associated with disease. Such approaches rely on 'tag' single nucleotide polymorphisms (SNPs). The associated SNPs are rarely functional variants, so the extrapolation of genetic association data to the identification of biologically meaningful findings can be a protracted undertaking. Integrative genomics aims to bridge the gap between genotype and phenotype.Systems biology, principally through network analysis, is emerging as a valuable way to identify biological pathways of relevance to complex genetic diseases. This review aims to highlight recent findings in systems biology related to JIA in an attempt to assist in the understanding of JIA pathogenesis and therapeutic target identification.
Topics: Arthritis, Juvenile; Gene Regulatory Networks; Genome-Wide Association Study; Genotype; Humans; Metabolic Networks and Pathways; Phenotype; Polymorphism, Single Nucleotide; Protein Interaction Maps; Systems Biology
PubMed: 27411317
DOI: 10.1186/s12969-016-0078-4 -
Journal of Clinical Immunology Jan 2023Systemic juvenile idiopathic arthritis associated with interstitial lung disease (SJIA-LD) represents a highly morbid subset of SJIA for which effective therapies are...
Systemic juvenile idiopathic arthritis associated with interstitial lung disease (SJIA-LD) represents a highly morbid subset of SJIA for which effective therapies are lacking. We report the case of a patient with refractory SJIA-LD who underwent treatment with MAS-825, an investigational bispecific monoclonal antibody targeting IL-1β and IL-18. MAS-825 treatment was associated with a marked reduction in total IL-18 and free IL-18 in both serum and bronchoalveolar lavage fluid (BAL). Baseline oxygen saturation, exercise tolerance, and quality of life metrics improved after treatment with MAS-825, while pulmonary function testing remained stable. Following treatment, the BAL showed no evidence of pulmonary alveolar proteinosis and inflammatory infiltrates were markedly reduced, reflected by decreased numbers of CD4 T-cells, CD8 T-cells, and macrophages. The patient was able to wean entirely off systemic corticosteroids and other biologics after 10 months of treatment with MAS-825 and experienced no side effects of the drug. This case demonstrates improvement in pulmonary symptoms, lung inflammation, and burden of immunomodulatory therapy after treatment with MAS-825 and suggests that simultaneous targeting of both IL-1β and IL-18 may be a safe and effective treatment strategy in SJIA-LD.
Topics: Humans; Interleukin-18; Arthritis, Juvenile; Quality of Life; Macrophage Activation Syndrome; Lung Diseases, Interstitial
PubMed: 36006569
DOI: 10.1007/s10875-022-01353-y -
Bosnian Journal of Basic Medical... Apr 2022Systemic juvenile idiopathic arthritis (SJIA) is a severe childhood-onset inflammatory disease characterized by arthritis accompanied by systemic auto-inflammation and...
Systemic juvenile idiopathic arthritis (SJIA) is a severe childhood-onset inflammatory disease characterized by arthritis accompanied by systemic auto-inflammation and extra-articular symptoms. While recent advances have unraveled a range of risk factors, the pathomechanisms involved in SJIA and potential prognostic markers for treatment success remain partly unknown. In this study, we included 70 active SJIA and 55 healthy control patients from the National Center for Biotechnology Information to analyze for differentially expressed genes (DEGs) using R. Functional enrichment analysis, protein-protein interaction (PPI), and gene module construction were performed for DEGs and hub gene set. We additionally examined immune system cell composition with CIBERSORT and predicted prognostic markers and potential treatment drugs for SJIA. In total, 94 upregulated and 24 downregulated DEGs were identified. Two specific modules of interest and eight hub genes (ARG1, DEFA4, HP, MMP8, MMP9, MPO, OLFM4, PGLYRP1) were screened out. Functional enrichment analysis suggested that complex neutrophil-related functions play a decisive role in the disease pathogenesis. CIBERSORT indicated neutrophils, M0 macrophages, CD8+ T cells, and naïve B cells to be relevant drivers of disease progression. Additionally, we identified TPM2 and GZMB as potential prognostic markers for treatment response to canakinumab. Moreover, sulindac sulfide, (-)-catechin, and phenanthridinone were identified as promising treatment agents. This study provides a new insight into molecular and cellular pathogenesis of active SJIA and highlights potential targets for further research.
Topics: Arthritis, Juvenile; Child; Computational Biology; Humans; Neutrophils; Prognosis
PubMed: 34480465
DOI: 10.17305/bjbms.2021.6016 -
Pediatric Rheumatology Online Journal Nov 2022The epidemiology and clinical presentation of systemic juvenile idiopathic arthritis (sJIA) in the Afro-Caribbean population is not well described.
INTRODUCTION
The epidemiology and clinical presentation of systemic juvenile idiopathic arthritis (sJIA) in the Afro-Caribbean population is not well described.
METHODS
Retrospective study conducted between January 2000 and January 2022 in the French Overseas Departments of America. Clinical data were obtained from multiple sources: computerized hospital archives, registries of referring pediatricians, and the French National Registry for rare diseases. The disease studied was sJIA defined according to international criteria.
RESULTS
Twenty-five patients were identified. Mean age at diagnosis was 7.5 years (range: 1.2-14.9 years) and mean duration of follow-up was 5.2 years (range: 0.5-16 years). All patients had joint involvement at diagnosis with 68% presenting inflammatory arthritis and 32% inflammatory joint pain. Sixteen percent had coronary involvement at onset. More than half (52%) suffered from macrophage activation syndrome (MAS) during childhood (32% at onset). The mean number of flares in childhood was 2 (Range: 1-5). Sixty-eight percent of patients had disease control during childhood without biotherapy. The most frequent second line treatment was anakinra (7/8). There was no difference in clinical or biological severity according to gender. The median duration of treatment during childhood was 5 months (range: 2-144) and 72% had a cumulative treatment duration of less than one year.
CONCLUSION
These patients of Afro-Caribbean origin suffering from sJIA showed some specificities, such as a higher rate of MAS and coronary involvement at onset. The incidence per year was stable over a 20-year period. Overall outcomes during childhood were similar to western countries.
Topics: Child; Humans; Arthritis, Juvenile; Retrospective Studies; Macrophage Activation Syndrome; Interleukin 1 Receptor Antagonist Protein; Caribbean Region
PubMed: 36384585
DOI: 10.1186/s12969-022-00766-8 -
Ophthalmology Apr 2021To assess the long-term outcome of uveitis in juvenile idiopathic arthritis (JIA).
PURPOSE
To assess the long-term outcome of uveitis in juvenile idiopathic arthritis (JIA).
DESIGN
Population-based, multicenter, prospective JIA cohort, with a cross-sectional assessment of JIA-associated uveitis (JIA-U) 18 years after the onset of JIA.
PARTICIPANTS
A total of 434 patients with JIA, of whom 96 had uveitis, from defined geographic areas of Denmark, Finland, Norway, and Sweden.
METHODS
Patients with onset of JIA between January 1997 and June 2000 were prospectively followed for 18 years. Pediatric rheumatologists and ophthalmologists collected clinical and laboratory data.
MAIN OUTCOME MEASURES
Cumulative incidence of uveitis and clinical characteristics, JIA and uveitis disease activity, ocular complications, visual outcome, and risk factors associated with the development of uveitis-related complications.
RESULTS
Uveitis developed in 96 (22.1%) of 434 patients with JIA. In 12 patients (2.8%), uveitis was diagnosed between 8 and 18 years of follow-up. Systemic immunosuppressive medication was more common among patients with uveitis (47/96 [49.0%]) compared with patients without uveitis (78/338 [23.1%]). Active uveitis was present in 19 of 78 patients (24.4%) at the 18-year visit. Ocular complications occurred in 31 of 80 patients (38.8%). Short duration between the onset of JIA and the diagnosis of uveitis was a risk factor for developing ocular complications (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.1-1.8). Patients with a diagnosis of uveitis before the onset of JIA all developed cataract and had an OR for development of glaucoma of 31.5 (95% CI, 3.6-274). Presence of antinuclear antibodies (ANAs) was also a risk factor for developing 1 or more ocular complications (OR, 3.0; 95% CI, 1.2-7.7). Decreased visual acuity (VA) <6/12 was found in 12 of 135 eyes (8.9%) with uveitis, and 4 of 80 patients (5.0%) with JIA-U had binocular decreased VA <6/12.
CONCLUSIONS
Our results suggest that uveitis screening should start immediately when the diagnosis of JIA is suspected or confirmed and be continued for more than 8 years after the diagnosis of JIA. Timely systemic immunosuppressive treatment in patients with a high risk of developing ocular complications must be considered early in the disease course to gain rapid control of ocular inflammation.
Topics: Arthritis, Juvenile; Child; Child, Preschool; Cohort Studies; Cross-Sectional Studies; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Incidence; Male; Prospective Studies; Risk Factors; Scandinavian and Nordic Countries; Uveitis
PubMed: 32866542
DOI: 10.1016/j.ophtha.2020.08.024 -
Pediatric Radiology Jun 2018Imaging is increasingly being integrated into clinical practice to improve diagnosis, disease control and outcome in children with juvenile idiopathic arthritis. Over... (Review)
Review
Imaging is increasingly being integrated into clinical practice to improve diagnosis, disease control and outcome in children with juvenile idiopathic arthritis. Over the last decades several international groups have been launched to standardize and validate different imaging techniques. To enhance transparency and facilitate collaboration, we present an overview of ongoing initiatives.
Topics: Arthritis, Juvenile; Child; Cooperative Behavior; Diagnostic Imaging; Humans; Internationality
PubMed: 29332166
DOI: 10.1007/s00247-017-4054-z -
Arthritis & Rheumatology (Hoboken, N.J.) Jul 2022An unusual form of lung disease has begun to affect some children with systemic juvenile idiopathic arthritis (JIA), coincident with increasing utilization of... (Review)
Review
An unusual form of lung disease has begun to affect some children with systemic juvenile idiopathic arthritis (JIA), coincident with increasing utilization of interleukin-1 (IL-1) and IL-6 antagonists. Many children with systemic JIA-associated lung disease (SJIA-LD) have a history of clinical and laboratory features resembling drug reaction with eosinophilia and systemic symptoms (DRESS), a presentation now convincingly associated with HLA-DRB1*15. Treatment of DRESS typically requires drug discontinuation, a daunting prospect for clinicians and families who rely upon these agents. Here we review SJIA-LD and its associated DRESS-like phenotype. We suggest an alternative explanation, the cytokine plasticity hypothesis, proposing that IL-1 and IL-6 blockers modulate the milieu in which T cells develop, leading to a pathologic immune response triggered through exposure to common microbes, or to other exogenous or endogenous antigens, rather than to the drugs themselves. This hypothesis differs from DRESS in mechanism but also in clinical implications, predicting that control of pathogenic T cells could permit continued use of IL-1 and IL-6 antagonists in some individuals. The spectrum posed by these two hypotheses provides a conceptual framework that will guide investigation into the pathogenesis of SJIA-LD and may open up new therapeutic avenues for patients with systemic JIA.
Topics: Arthritis, Juvenile; Drug Hypersensitivity; Humans; Interleukin-1; Interleukin-6; Lung Diseases
PubMed: 35413159
DOI: 10.1002/art.42137 -
Rheumatic Diseases Clinics of North... May 2016Patient-reported outcome (PRO) measures provide a valuable window into how patients with juvenile idiopathic arthritis and their parents perceive their functioning,... (Review)
Review
Patient-reported outcome (PRO) measures provide a valuable window into how patients with juvenile idiopathic arthritis and their parents perceive their functioning, quality of life, and medication side effects in the context of their disease and treatment. Momentum behind adoption of PRO measures is increasing as these patient-relevant tools capture information pertinent to taking a patient-centered approach to health care and research. This article reviews the clinical and research utility of obtaining PROs across domains applicable to the experience of juvenile idiopathic arthritis and summarizes available self-report and parent-proxy PRO measures. Current challenges and limitations of PRO usage are discussed.
Topics: Activities of Daily Living; Antirheumatic Agents; Arthralgia; Arthritis, Juvenile; Biomedical Research; Humans; Patient Reported Outcome Measures; Patient-Centered Care; Quality of Life; Treatment Outcome
PubMed: 27133493
DOI: 10.1016/j.rdc.2016.01.004