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Pediatric Radiology Jun 2018In juvenile idiopathic arthritis (JIA), imaging is increasingly used in clinical practice. In this paper we discuss imaging of the knee, the clinically most commonly... (Review)
Review
In juvenile idiopathic arthritis (JIA), imaging is increasingly used in clinical practice. In this paper we discuss imaging of the knee, the clinically most commonly affected joint in JIA. In the last decade, a number of important steps have been made in the development of imaging outcome measures in children with JIA knee involvement. Ultrasound is undergoing a fast validation process, which should be accomplished within the next few years. The validation processes of MRI as an imaging biomarker for clinical trials in the JIA knee are at an advanced stage, with important data available on the feasibility, reliability and validity of the Juvenile Arthritis MRI Scoring system. Moreover, both US and MRI data are emerging on the normal appearance of the growing knee joint.
Topics: Arthritis, Juvenile; Child; Diagnosis, Differential; Humans; Knee Joint
PubMed: 29766248
DOI: 10.1007/s00247-017-4015-6 -
Clinical and Experimental Medicine Jul 2023Juvenile idiopathic arthritis (JIA) is a common pediatric rheumatic disease. Renal manifestations have been rarely observed in JIA, although amyloidosis could be a renal... (Review)
Review
Juvenile idiopathic arthritis (JIA) is a common pediatric rheumatic disease. Renal manifestations have been rarely observed in JIA, although amyloidosis could be a renal complication in systemic JIA (sJIA). To investigate renal damage in JIA children and to establish the relationship with treatment. Blood urea nitrogen (BUN), creatinine, cystatin C (CysC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), urinary albumin excretion (UAE), estimated glomerular filtration rate (eGFR), and renal resistive index (RRI) were assessed in 49 JIA children (9 boys/40 girls, mean age 10.3 ± 3.8 years) and in 49 healthy controls (24 boys/25 girls, mean age 11.3 ± 3.4 years). Twenty-two JIA patients were on methotrexate (MTX) therapy (group A) and 27 on biologic drugs (group B). CysC and BUN (respectively, 0.8 ± 0.1 vs. 0.7 ± 0.1 mg/dl; 13.3 ± 2.9 vs. 11.7 ± 1.4 mg/dl) were higher (p ≤ 0.001) whereas creatinine and eGFR (respectively, 0.5 ± 0.1 vs. 0.6 ± 0.1 mg/dl; 99.2 ± 10.5 vs. 122.5 ± 19.8 ml/min/1.73 m) were lower in JIA children as compared to controls (p < 0.001). UAE resulted higher in patients than in controls (p = 0.003). Mean RRI was higher in JIA children than controls (0.7 ± 0.04 vs. 0.6 ± 0.04; p < 0.001). Group B showed higher mean RRI than group A (0.7 ± 0.1 vs. 0.7 ± 0.04; p < 0.001). Associations were found between RRI and ESR, JADAS-27, disease state, BMI-SDS (p < 0.001), CRP (p = 0.003) and eGFR (p = 0.001). JIA children had reduced eGFR, increased UAE and higher RRI values, than controls. RRIs were higher in patients on biologic drugs than MTX group and were associated with inflammation indexes and disease state, suggesting a direct effect of the disease.
Topics: Male; Female; Child; Humans; Adolescent; Arthritis, Juvenile; Creatinine; Methotrexate; Kidney; Inflammation
PubMed: 36129558
DOI: 10.1007/s10238-022-00898-x -
Autoimmunity Reviews Jun 2022Antinuclear antibodies (ANA) detected in juvenile idiopathic arthritis (JIA) sera are considered to be a biomarker for JIA-related uveitis. There is an unclear consensus... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antinuclear antibodies (ANA) detected in juvenile idiopathic arthritis (JIA) sera are considered to be a biomarker for JIA-related uveitis. There is an unclear consensus on the screening dilutions of ANA as detected by the HEp-2 indirect immunofluorescence assay (IFA) that should be used when predicting the risk of uveitis in JIA. The primary aim of this systematic review and meta-analysis was to summarize the evidence regarding ANA prevalence and performance in JIA and JIA-associated uveitis.
METHODS
A search of five databases identified 1766 abstracts, using the search terms juvenile idiopathic arthritis; pediatric; sensitivity or diagnostic; and ANA. Studies that met inclusion/exclusion criteria were analyzed for the proportion of JIA patients with a positive ANA. Forest plots and pooled estimates were generated for the proportion of JIA patients and those with uveitis who were positive for ANA stratified by screening dilution. Study heterogeneity was also assessed.
RESULTS
Twenty-eight studies met inclusion criteria yielding 6250 unique patients; 5902 had JIA and 348 were healthy controls or were known to have other autoimmune diseases. The most reported IFA serum screening dilution was ≥1:80, representing 41.9% of patients and this screening dilution had the highest proportion of JIA ANA positivity (41.0%; 95% CI 25.0%-57.0%). ANA screening for JIA uveitis had a sensitivity and specificity of ANA at ≥1:40 of 75% (95% CI 46%-100%) and 66% (95% CI 39%-93%), respectively. There was significant study heterogeneity across both JIA subtypes and ANA titres.
CONCLUSIONS
Although there was a large variation of ANA IFA screening dilutions used for investigation of JIA, the most common dilution was 1:80. The current literature has several important deficiencies that are identified in this review requiring additional studies to inform the ANA screening dilutions of clinical value in JIA and JIA-associated uveitis.
Topics: Antibodies, Antinuclear; Arthritis, Juvenile; Child; Fluorescent Antibody Technique, Indirect; Humans; Prevalence; Retrospective Studies; Uveitis
PubMed: 35398272
DOI: 10.1016/j.autrev.2022.103086 -
International Journal of Molecular... Oct 2022Systemic juvenile idiopathic arthritis (sJIA) and its complication, macrophage activation syndrome (sJIA-MAS), are rare but sometimes very serious or even critical... (Review)
Review
Systemic juvenile idiopathic arthritis (sJIA) and its complication, macrophage activation syndrome (sJIA-MAS), are rare but sometimes very serious or even critical diseases of childhood that can occasionally be characterized by nonspecific clinical signs and symptoms at onset-such as non-remitting high fever, headache, rash, or arthralgia-and are biologically accompanied by an increase in acute-phase reactants. For a correct positive diagnosis, it is necessary to rule out bacterial or viral infections, neoplasia, and other immune-mediated inflammatory diseases. Delays in diagnosis will result in late initiation of targeted therapy. A set of biomarkers is useful to distinguish sJIA or sJIA-MAS from similar clinical entities, especially when arthritis is absent. Biomarkers should be accessible to many patients, with convenient production and acquisition prices for pediatric medical laboratories, as well as being easy to determine, having high sensitivity and specificity, and correlating with pathophysiological disease pathways. The aim of this review was to identify the newest and most powerful biomarkers and their synergistic interaction for easy and accurate recognition of sJIA and sJIA-MAS, so as to immediately guide clinicians in correct diagnosis and in predicting disease outcomes, the response to treatment, and the risk of relapses. Biomarkers constitute an exciting field of research, especially due to the heterogeneous nature of cytokine storm syndromes (CSSs) in the COVID era. They must be selected with utmost care-a fact supported by the increasingly improved genetic and pathophysiological comprehension of sJIA, but also of CSS-so that new classification systems may soon be developed to define homogeneous groups of patients, although each with a distinct disease.
Topics: Humans; Child; Macrophage Activation Syndrome; Arthritis, Juvenile; COVID-19; Biomarkers
PubMed: 36361547
DOI: 10.3390/ijms232112757 -
International Journal of Molecular... Sep 2020Juvenile idiopathic arthritis and adult rheumatoid arthritis are two major groups with chronic joint pain and inflammation, extra-articular manifestations, and high risk... (Review)
Review
Juvenile idiopathic arthritis and adult rheumatoid arthritis are two major groups with chronic joint pain and inflammation, extra-articular manifestations, and high risk of comorbidities, which can cause physical and ocular disability, as well as create great socio-economic pressure worldwide. The pathogenesis of arthritis manifested in childhood and adulthood is multifactorial, unclear, and overly complex, in which immunity plays an important role. Although there are more and more biological agents with different mechanisms of action for the treatment of arthritis, the results are not as expected, because there are partial responses or non-responsive patients to these compounds, high therapeutic costs, side effects, and so on; therefore, we must turn our attention to other therapeutic modalities. Updating knowledge on molecular and cellular mechanisms in the comparative pathogenesis of chronic arthritis in both children and adults is necessary in the early and correct approach to treatment. Photobiomodulation (PBM) represents a good option, offering cost-effective advantages over drug therapy, with a quicker, more positive response to treatment and no side effects. The successful management of PBM in arthritis is based on the clinician's ability to evaluate correctly the inflammatory status of the patient, to seek the optimal solution, to choose the best technology with the best physical parameters, and to select the mode of action to target very precisely the immune system and the molecular signaling pathways at the molecular level with the exact amount of quantum light energy in order to obtain the desired immune modulation and the remission of the disease. Light is a very powerful tool in medicine because it can simultaneously target many cascades of immune system activation in comparison with drugs, so PBM can perform very delicate tasks inside our cells to modulate cellular dysfunctions, helping to initiate self-organization phenomena and finally, healing the disease. Interdisciplinary teams should work diligently to meet these needs by also using single-cell imaging devices for multispectral laser photobiomodulation on immune cells.
Topics: Adolescent; Adult; Aged; Arthritis; Arthritis, Juvenile; Arthritis, Rheumatoid; Child; Female; Humans; Inflammation; Low-Level Light Therapy; Male; Middle Aged
PubMed: 32911717
DOI: 10.3390/ijms21186565 -
RMD Open Aug 2023Early antibiotic exposure influences the gut microbiota which is believed to be involved in the pathogenesis of juvenile idiopathic arthritis (JIA). We aimed to...
OBJECTIVES
Early antibiotic exposure influences the gut microbiota which is believed to be involved in the pathogenesis of juvenile idiopathic arthritis (JIA). We aimed to investigate the association between systemic antibiotics in prenatal and early life and risk of JIA.
METHODS
We conducted a register-based cohort study including all children born in Norway from 2004 through 2012. The children were followed until 31 December 2020. Main exposures were dispensed antibiotics to the mother during pregnancy and to the child during 0-24 months of age. The outcome was defined by diagnostic codes indicating JIA. Multivariate logistic regression analyses were performed to estimate the association between antibiotic exposure and JIA.
RESULTS
We included 535 294 children and their mothers in the analyses; 1011 cases were identified. We found an association between exposure to systemic antibiotics during 0-24 months and JIA (adjusted OR (aOR) 1.40, 95% CI 1.24 to 1.59), with a stronger association for >1 course (aOR 1.50, 95% CI 1.29 to 1.74) vs 1 course (aOR 1.31, 95% CI 1.13 to 1.53). Subanalyses showed significant associations in all age periods except 0-6 months, and stronger association with sulfonamides/trimethoprim and broad-spectrum antibiotics. There was no association between prenatal antibiotic exposure and JIA.
CONCLUSIONS
The novel observation of no association with prenatal antibiotic exposure and JIA suggests that the association between antibiotics in early life and JIA is unlikely to be confounded by shared family factors. This may indicate that exposure to antibiotics in early life is an independent risk factor for JIA.
Topics: Child; Female; Pregnancy; Humans; Infant, Newborn; Infant; Arthritis, Juvenile; Cohort Studies; Anti-Bacterial Agents; Gastrointestinal Microbiome; Norway
PubMed: 37648397
DOI: 10.1136/rmdopen-2023-003333 -
Current Opinion in Rheumatology Sep 2015To review recent advances in the management strategies of polyarticular course juvenile idiopathic arthritis (JIA) and identify unanswered questions and avenues for... (Review)
Review
PURPOSE OF REVIEW
To review recent advances in the management strategies of polyarticular course juvenile idiopathic arthritis (JIA) and identify unanswered questions and avenues for further research.
RECENT FINDINGS
There is evidence for an early, aggressive, treat-to-target approach for polyarticular JIA. Clinical disease activity criteria have been recently defined and validated, including criteria for inactive disease and the juvenile arthritis disease activity score (JADAS). There is a need for evidence-based, defined disease targets and biomarkers for prediction of response, including targets for remission induction, and guidelines on drug withdrawal. Recent treatment consensus plans and guidelines are discussed and compared, including the 2015 NHS England clinical policy statement, the 2014 Childhood Arthritis and Rheumatology Research Alliance (CARRA) treatment plans and the 2011 American College of Rheumatology (ACR) guidelines. Evidence for new agents such as tocilizumab, rituximab, golimumab, ustekinumab, certolizumab and tofacitinib is promising: the recent clinical trials are summarized here. Stratification of individual patient treatment remains a goal, and predictive biomarkers have been shown to predict success in the withdrawal of methotrexate therapy.
SUMMARY
There are promising advances in the treatment approaches, disease activity criteria, clinical guidelines, pharmaceutical choices and individually stratified therapy choices for polyarticular JIA.
Topics: Antibodies, Monoclonal; Arthritis; Arthritis, Juvenile; Child; Enzyme Inhibitors; Guidelines as Topic; Humans; Treatment Outcome
PubMed: 26147756
DOI: 10.1097/BOR.0000000000000206 -
American Journal of Ophthalmology Jan 2018To describe the phenotype of the uveitis that accompanies juvenile psoriatic arthritis or psoriasis. (Observational Study)
Observational Study
PURPOSE
To describe the phenotype of the uveitis that accompanies juvenile psoriatic arthritis or psoriasis.
DESIGN
Observational case series.
METHODS
Setting: Two university-based referral clinics: 1 in England, 1 in the United States.
STUDY POPULATION
Five children with uveitis and psoriatic arthritis and 1 with uveitis and psoriasis Observational Procedure: Retrospective chart review.
MAIN OUTCOME MEASURES
Demographics of subjects such as age and sex; description of ocular and joint disease; surgical and other complications; medical treatment.
RESULTS
Five of the 6 children in this series had the onset of disease at or before age 6 (P = .0008 compared to expected age of onset for psoriatic arthritis in childhood). All children in this series had an inadequate response to topical corticosteroids. Most of the children were treated with systemic corticosteroids for many months, yet all of them went on to require methotrexate. Therapy with systemic methotrexate did not suffice, as all the patients also required some form of biologic therapy. Five of 6 had surgeries such as vitrectomy, cataract extraction, or a procedure for glaucoma control.
CONCLUSIONS
The observations suggest that the uveitis that accompanies juvenile psoriatic arthritis might be a distinct disease that is particularly severe when its onset affects children aged 6 years or younger.
Topics: Age of Onset; Arthritis, Juvenile; Child; Child, Preschool; England; Female; Humans; Incidence; Male; Phenotype; Psoriasis; Risk Factors; United States; Uveitis
PubMed: 29101009
DOI: 10.1016/j.ajo.2017.10.018 -
Pediatric Rheumatology Online Journal May 2024Juvenile Idiopathic Arthritis (JIA) is a condition that occurs when individuals under the age of 16 develop arthritis that lasts for more than six weeks, and the cause...
BACKGROUND
Juvenile Idiopathic Arthritis (JIA) is a condition that occurs when individuals under the age of 16 develop arthritis that lasts for more than six weeks, and the cause is unknown. The development of JIA may be linked to serum metabolites. Nevertheless, the association between JIA pathogenesis and serum metabolites is unclear, and there are discrepancies in the findings across studies.
METHODS
In this research, the association between JIA in humans and 486 serum metabolites was assessed using genetic variation data and genome-wide association study. The identification of causal relationships was accomplished through the application of univariate Mendelian randomization (MR) analysis. Various statistical methods, including inverse variance weighted and MR-Egger, were applied to achieve this objective. To ensure that the findings from the MR analysis were trustworthy, a number of assessments were carried out. To ensure the accuracy of the obtained results, a range of techniques were utilised including the Cochran Q test, examination of the MR-Egger intercept, implementation of the leave-one-out strategy, and regression analysis of linkage disequilibrium scores. In order to identify the specific metabolic pathways associated with JIA, our primary objective was to perform pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes.
RESULTS
Two-sample summary data MR analyses and sensitivity analyses showed that five metabolites were significantly causally associated with JIA, including two risk factors-kynurenine (odds ratio [OR]: 16.39, 95% confidence interval [CI]: 2.07-129.63, p = 5.11 × 10) and linolenate (OR: 16.48, 95% CI: 1.32-206.22, p = 0.030)-and three protective factors-3-dehydrocarnitine (OR: 0.32, 95% CI: 0.14-0.72, p = 0.007), levulinate (4-oxovalerate) (OR: 0.40, 95% CI: 0.20-0.80, p = 0.010), and X-14,208 (phenylalanylserine) (OR: 0.68, 95% CI: 0.51-0.92, p = 0.010). Furthermore, seven metabolic pathways, including α-linolenic acid metabolism and pantothenate and CoA biosynthesis, are potentially associated with the onset and progression of JIA.
CONCLUSION
Five serum metabolites, including kynurenine and 3-dehydrocarnitine, may be causally associated with JIA. These results provide a theoretical framework for developing effective JIA prevention and screening strategies.
Topics: Humans; Arthritis, Juvenile; Mendelian Randomization Analysis; Genome-Wide Association Study; Child; Polymorphism, Single Nucleotide; Kynurenine
PubMed: 38724970
DOI: 10.1186/s12969-024-00986-0 -
The Journal of Clinical Investigation Nov 2023Systemic autoimmune and autoinflammatory diseases are characterized by genetic and cellular heterogeneity. While current single-cell genomics methods provide insights...
Systemic autoimmune and autoinflammatory diseases are characterized by genetic and cellular heterogeneity. While current single-cell genomics methods provide insights into known disease subtypes, these analysis methods do not readily reveal novel cell-type perturbation programs shared among distinct patient subsets. Here, we performed single-cell RNA-Seq of PBMCs of patients with systemic juvenile idiopathic arthritis (SJIA) with diverse clinical manifestations, including macrophage activation syndrome (MAS) and lung disease (LD). We introduced two new computational frameworks called UDON and SATAY-UDON, which define patient subtypes based on their underlying disrupted cellular programs as well as associated biomarkers or clinical features. Among twelve independently identified subtypes, this analysis uncovered what we believe to be a novel complement and interferon activation program identified in SJIA-LD monocytes. Extending these analyses to adult and pediatric lupus patients found new but also shared disease programs with SJIA, including interferon and complement activation. Finally, supervised comparison of these programs in a compiled single-cell pan-immune atlas of over 1,000 healthy donors found a handful of normal healthy donors with evidence of early inflammatory activation in subsets of monocytes and platelets, nominating possible biomarkers for early disease detection. Thus, integrative pan-immune single-cell analysis resolved what we believe to be new conserved gene programs underlying inflammatory disease pathogenesis and associated complications.
Topics: Adult; Humans; Child; Arthritis, Juvenile; Biomarkers; Lung Diseases; Interferons; Genomics
PubMed: 37733441
DOI: 10.1172/JCI166741