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American Journal of Ophthalmology Aug 2021To determine classification criteria for juvenile idiopathic arthritis (JIA)-associated chronic anterior uveitis (CAU).
PURPOSE
To determine classification criteria for juvenile idiopathic arthritis (JIA)-associated chronic anterior uveitis (CAU).
DESIGN
Machine learning of cases with JIA CAU and 8 other anterior uveitides.
METHODS
Cases of anterior uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the anterior uveitides. The resulting criteria were evaluated on the validation set.
RESULTS
One thousand eighty-three cases of anterior uveitides, including 202 cases of JIA CAU, were evaluated by machine learning. The overall accuracy for anterior uveitides was 97.5% in the training set and 96.7% in the validation set (95% confidence interval 92.4, 98.6). Key criteria for JIA CAU included (1) chronic anterior uveitis (or, if newly diagnosed, insidious onset) and (2) JIA, except for the systemic, rheumatoid factor-positive polyarthritis, and enthesitis-related arthritis variants. The misclassification rates for JIA CAU were 2.4% in the training set and 0% in the validation set.
CONCLUSIONS
The criteria for JIA CAU had a low misclassification rate and seemed to perform well enough for use in clinical and translational research.
Topics: Adult; Arthritis, Juvenile; Chronic Disease; Consensus; Female; Humans; Male; Middle Aged; Uveitis, Anterior; Young Adult
PubMed: 33845021
DOI: 10.1016/j.ajo.2021.03.055 -
Pediatric Rheumatology Online Journal Oct 2023Anakinra is a recombinant interleukin-1 (IL-1) receptor antagonist used in systemic juvenile idiopathic arthritis (sJIA), refractory Kawasaki disease (KD) and...
BACKGROUND
Anakinra is a recombinant interleukin-1 (IL-1) receptor antagonist used in systemic juvenile idiopathic arthritis (sJIA), refractory Kawasaki disease (KD) and cryopyrin-associated autoinflammatory syndrome (CAPS). Anakinra associated hepatotoxicity, while rare, has been described in several cases in daily practice. In this case series the authors describe three pediatric patients with this side effect in the setting of severe macrophage activation syndrome (MAS) in KD and sJIA.
CASE PRESENTATION
The first patient was a 12-year-old boy who presented with fever, maculo-papular exanthema and polyarthralgia. Tonsillitis, distal limb induration and tender cervical lymph nodes were observed. Erythrocyte-sedimentation rate (ESR), C-reactive protein (CRP), ferritin (11,975 ng/mL), D-dimers (5,98 mg/L FEU) and soluble CD25 (3645 pg/mL) levels were elevated. Exclusion of sepsis / toxic shock syndrome warranted introduction of IV methylprednisolone and immunoglobulin (IG IV), with partial response. A MAS secondary to KD was assumed, and anakinra 2 mg/kg/day was introduced. Twenty days later he developed new-onset nausea and severe cyto-cholestasis, normalizing after 2 months of drug discontinuation. Posterior onset of polyarthritis and evanescent lead to a final diagnosis of sJIA. The second patient was a 2-year-old boy with a 10-day history of fevers, generalized rash, hepatosplenomegaly and strawberry tongue. Leucocytosis with neutrophilia and elevated CRP were observed. Initial treatment with IVIG in the setting of incomplete KD was ineffective. Mild anaemia, leukopenia and very high serum ferritin (maximum 26,128 ng/mL) ensued. Presumptive sJIA associated MAS was treated with IV methylprednisolone and anakinra 2 mg/kg/day, with prompt response. Four weeks later transaminitis was detected, and temporary anakinra suspension led to normalisation of laboratorial values. The third case related to a 4-year-old boy presenting with fever, maculopapular rash and cervical lymphadenopathy. CRP and ESR were elevated, and KD was diagnosed. IVIG and methylprednisolone were initiated with clinical worsening, warranting for anakinra introduction at 2 mg/kg/day. After three weeks, liver enzymes progressively elevated, resolving on 2 weeks of anakinra discontinuation.
CONCLUSIONS
To the best of our knowledge, this is the first case series describing anakinra associated hepatotoxicity in pediatric patients with rheumatic diseases other than sJIA, bringing additional insight to therapeutic monitoring in patients undergoing this treatment.
Topics: Male; Humans; Child; Child, Preschool; Interleukin 1 Receptor Antagonist Protein; Immunoglobulins, Intravenous; Rheumatology; Fever; Drug-Related Side Effects and Adverse Reactions; Arthritis, Juvenile; Exanthema; Methylprednisolone; Macrophage Activation Syndrome; Ferritins; Chemical and Drug Induced Liver Injury
PubMed: 37803456
DOI: 10.1186/s12969-023-00891-y -
Pediatric Rheumatology Online Journal Oct 2023Physiotherapy appears as a promising therapy option for patients with Juvenile Idiopathic Arthritis (JIA) [1, 2], but the effects of physiotherapy and jaw exercises on...
BACKGROUND
Physiotherapy appears as a promising therapy option for patients with Juvenile Idiopathic Arthritis (JIA) [1, 2], but the effects of physiotherapy and jaw exercises on JIA-related orofacial symptoms remain unknown [3]. The aim of this proof-of-concept study was to assess the impact of orofacial physiotherapy and home-exercise programs in patients with JIA and temporomandibular joint (TMJ) involvement.
METHODS
Twelve patients with JIA and TMJ involvement received a treatment of physiotherapy, complemented by prescribed home exercises spanning over eight weeks. Orofacial symptoms and dysfunction were monitored pre-treatment, during treatment, after treatment, and at a three-months follow-up.
RESULTS
Orofacial pain frequency and intensity significantly decreased during the course of the treatment (p = 0.009 and p = 0.006), with further reductions observed at the three-month follow-up (p = 0.007 and p = 0.002). During treatment, the mandibular function improved significantly in terms of maximal mouth opening capacity, laterotrusion, and protrusion.
CONCLUSIONS
This proof-of-concept study shows favourable effects of physiotherapy and home excercises in the management of JIA-related orofacial symptoms and dysfunctions.
Topics: Humans; Arthritis, Juvenile; Temporomandibular Joint Disorders; Temporomandibular Joint; Facial Pain; Physical Therapy Modalities
PubMed: 37828517
DOI: 10.1186/s12969-023-00900-0 -
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 -
Pediatric Rheumatology Online Journal Jun 2022A significant proportion of children and young people with juvenile idiopathic arthritis (JIA) do not achieve inactive disease during the first two years following...
BACKGROUND
A significant proportion of children and young people with juvenile idiopathic arthritis (JIA) do not achieve inactive disease during the first two years following diagnosis. Refinements to clinical care pathways have the potential to improve clinical outcomes but a lack of consistent and contemporaneous clinical data presently precludes standard setting and implementation of meaningful quality improvement programmes. This study was the first to pilot clinical data collection and analysis using the CAPTURE-JIA dataset, and to explore patient and clinician-reported feasibility and acceptability data.
METHODS
A multiphase mixed-methods approach enabled prospective collection of quantitative data to examine the feasibility and efficacy of dataset collection and of qualitative data informing the context and processes of implementation. An initial paper pilot informed the design of a bespoke electronic data collection system (the Agileware system), with a subsequent electronic pilot informing the final CAPTURE-JIA data collection tool.
RESULTS
Paper collection of patient data was feasible but time-consuming in the clinical setting. Phase 1 paper pilot data (121 patients) identified three themes: problematic data items (14/62 data items received >40% missing data), formatting of data collection forms and a clinician-highlighted need for digital data collection, informing Phase 2 electronic data collection tool development. Patients and families were universally supportive of the collection and analysis of anonymised patient data to inform clinical care. No apparent preference for paper / electronic data collection was reported by families. Phase 3 electronic pilot data (38 patients) appeared complete and the system reported to be easy to use. Analysis of the study dataset and a dummy longitudinal dataset confirmed that all eleven JIA national audit questions can be answered using the electronic system.
CONCLUSIONS
Multicentre CAPTURE-JIA data collection is feasible and acceptable, with a bespoke data collection system highlighted as the most satisfactory solution. The study is informing ongoing work towards a streamlined and flexible national paediatric data collection system to drive quality improvement in clinical care.
Topics: Adolescent; Arthritis, Juvenile; Child; Data Collection; Humans; Longitudinal Studies; Prospective Studies; Quality Improvement
PubMed: 35717328
DOI: 10.1186/s12969-022-00697-4 -
Pediatric Rheumatology Online Journal Nov 2023Juvenile idiopathic arthritis (JIA) is a broad term used to describe arthritis of unknown origin. JIA commonly persists into adulthood, often causing substantial...
OBJECTIVE
Juvenile idiopathic arthritis (JIA) is a broad term used to describe arthritis of unknown origin. JIA commonly persists into adulthood, often causing substantial morbidity such as restricted joint function, which can lead to challenges in employment and independence. This study aims to identify diagnostic biomarkers and investigate the role of immune cells in the pathogenesis of rheumatoid factor-negative polyarticular juvenile idiopathic arthritis (RF-negative pJIA) and oligoarticular juvenile idiopathic arthritis (oJIA).
METHODS
We retrieved a JIA dataset from the GEO database and conducted an analysis of differentially expressed genes (DEGs). Subsequently, functional enrichment analysis was performed on the DEGs. Weighted gene co-expression network analysis (WGCNA) was utilized to identify key modules. Additionally, we constructed a protein‒protein interaction network to identify hub genes that serve as signature genes. Furthermore, we employed CIBERSORT to classify immune cell infiltration.
RESULTS
From the GSE20307 dataset, we identified a total of 1438 DEGs in RF-negative pJIA and 688 DEGs in oJIA. WGCNA clustered the data into 6 modules in pJIA and 4 modules in oJIA. Notably, the ME5 and ME2 modules exhibited significant associations with pJIA and oJIA, respectively. In both pJIA and oJIA, we identified six hub genes, four of which demonstrated high diagnostic sensitivity and specificity in pJIA, while five showed high diagnostic sensitivity and specificity in oJIA. CIBERSORT analysis suggested the potential involvement of these signature genes in immune cell infiltration.
CONCLUSION
In this study, we identified JUN, CXCL8, SOCS3, and KRAS as biomarkers for RF-negative pJIA and JUN, CXCL8, SOCS3, PTGS2, and NFKBIA as biomarkers for oJIA. Furthermore, our findings suggest that Tfh cells may play a role in the early onset of both RF-negative pJIA and oJIA.
Topics: Humans; Arthritis, Juvenile; Biomarkers; Gene Expression Profiling; Sensitivity and Specificity
PubMed: 38001449
DOI: 10.1186/s12969-023-00926-4 -
Pediatric Rheumatology Online Journal Sep 2023Childhood-onset rheumatoid arthritis (CORA), known as rheumatoid factor (RF)-positive juvenile idiopathic arthritis is a type of juvenile idiopathic arthritis that...
BACKGROUND
Childhood-onset rheumatoid arthritis (CORA), known as rheumatoid factor (RF)-positive juvenile idiopathic arthritis is a type of juvenile idiopathic arthritis that shares the same genetic factors and clinical features as adult-onset rheumatoid arthritis. In Africa, CORA hasn't been the subject of a specific study.
OBJECTIVES
The aim of this study is to describe the clinical features, disease activity, functional disability, and treatment of CORA at diagnosis in Senegal and compare the findings to other CORA populations.
METHODS
We conducted a mixed cohort study by reviewing the medical records of patients diagnosed with CORA with an age of symptom onset < 18 years according to the 2019 PRINTO provisional criteria for RF-positive JIA from January 2020 to December 2022 at rheumatology department of Aristide Le Dantec Hospital in Dakar, Senegal. We collected demographic, clinical, paraclinical and therapeutic data. Disease activity score was assessed by DAS28-ESR and DAS28-CRP. Functional disability was assessed using Health Assessment Questionnaire (HAQ) or Childhood HAQ.
RESULTS
A total of 21 patients were included. Eighteen (85.7%) were Females. The mean age at symptom onset was 13.0 ± 3.0 years, and at diagnosis was 16.4 ± 4.2 years. Morning stiffness, joint swelling, and joint deformities were found in 20, 18 and 13 patients respectively. Four patients had a family history of rheumatoid arthritis. Five patients had extra-articular involvement such as rheumatoid nodules. Two patients had interstitial lung disease. The biological inflammatory syndrome was found in 90% of cases. 16 of 21 (76.2%) patients had positive RF, and 18 of 20 (90%) patients had positive Anti-CCP. Seven of 12 (58.3%) patients had positive anti-nuclear antibodies. The mean DAS28-ESR was 5.7 ± 1.0. Fifteen (71.4%) patients had high disease activity (DAS28-ESR > 5.1). The mean DAS28-CRP was 5.4 ± 1.1. The median HAQ was 2.12 with a mean HAQ of 1.9. Nineteen (90.5%) patients were treated with methotrexate, while 17 (81%) had a combination of methotrexate and hydroxychloroquine. Oral prednisone was used in 17 (81%) cases. Non-steroidal anti-inflammatory drugs were used in 4 cases (19%). After 6 months of treatment, mean DAS28-CRP was 2.9.
CONCLUSION
In our study, CORA mainly affects 13-year-old girls, characterised by high disease activity with joint deformity and significant functional impairment. Treatment is mainly based on methotrexate, prednisone and hydroxychloroquine. Further studies are needed to determine the exact clinical phenotype of this disease.
Topics: Child; Adult; Female; Humans; Adolescent; Male; Senegal; Tertiary Care Centers; Arthritis, Juvenile; Methotrexate; Hydroxychloroquine; Prednisone; Cohort Studies; Africa, Western; Arthritis, Rheumatoid; Rheumatoid Factor
PubMed: 37700346
DOI: 10.1186/s12969-023-00889-6 -
Frontiers in Immunology 2021Systemic juvenile idiopathic arthritis (sJIA) is an immune disorder characterized by fever, skin rash, arthritis and splenomegaly. Recently, increasing number of sJIA...
Systemic juvenile idiopathic arthritis (sJIA) is an immune disorder characterized by fever, skin rash, arthritis and splenomegaly. Recently, increasing number of sJIA patients were reported having lung disease. Here, we explored lung abnormalities in a mouse model for sJIA relying on injection of IFN-γ deficient (IFN-γ KO) mice with complete Freund's adjuvant (CFA). Monitoring of lung changes during development of sJIA using microcomputer tomography revealed a moderate enlargement of lungs, a decrease in aerated and increase in non-aerated lung density. When lung function and airway reactivity to methacholine was assessed, gender differences were seen. While male mice showed an increased tissue hysteresivity, female animals were characterized by an increased airway hyperactivity, mirroring ongoing inflammation. Histologically, lungs of sJIA-like mice showed subpleural and parenchymal cellular infiltrates and formation of small granulomas. Flow cytometric analysis identified immature and mature neutrophils, and activated macrophages as major cell infiltrates. Lung inflammation in sJIA-like mice was accompanied by augmented expression of IL-1β and IL-6, two target cytokines in the treatment of sJIA. The increased expression of granulocyte colony stimulating factor, a potent inducer of granulopoiesis, in lungs of mice was striking considering the observed neutrophilia in patients. We conclude that development of sJIA in a mouse model is associated with lung inflammation which is distinct to the lung manifestations seen in sJIA patients. Our observations however underscore the importance of monitoring lung disease during systemic inflammation and the model provides a tool to explore the underlying mechanism of lung pathology in an autoinflammatory disease context.
Topics: Animals; Arthritis, Juvenile; Disease Models, Animal; Female; Freund's Adjuvant; Inflammation; Inflammation Mediators; Interferon-gamma; Lung; Macrophage Activation; Male; Mice; Mice, Inbred BALB C
PubMed: 33777039
DOI: 10.3389/fimmu.2021.642778 -
Minerva Stomatologica Apr 2017The possible relationship between periodontitis and juvenile idiopathic arthritis (JIA) is now mostly unknown but there are common characteristics in these two diseases....
BACKGROUND
The possible relationship between periodontitis and juvenile idiopathic arthritis (JIA) is now mostly unknown but there are common characteristics in these two diseases. The purpose of this study is to evaluate etanercept (Enbrel®) effects on periodontal conditions of children affected by JIA.
METHODS
For this study three group of patients were selected. The first one is represented by JIA subjects in pharmacologic therapy with etanercept (Enbrel®). The second one was composed by subjects in pharmacologic therapy with other drugs and the third one by healthy subjects. Twenty subjects for each group were selected. For each subject two periodontal scores were taken: Plaque Index and bleeding on probing. In order to check the reliability of the method a second registration has been performed in all the 3 groups after one month. A statistic Kruskal-Wallis test was performed.
RESULTS
The average Plaque Index was 48% in the first group, 37% in the second group and 20% in the control group. The average Bleeding Index was 5% in the first group, 5% in the second group and 9% in the control group.
CONCLUSIONS
Etanercept seems to reduce periodontal inflammation in children affected by JIA as the other therapy.
Topics: Adolescent; Age of Onset; Antirheumatic Agents; Arthritis, Juvenile; Child; Child, Preschool; Dental Plaque Index; Etanercept; Female; Gingival Hemorrhage; Humans; Male; Periodontal Diseases
PubMed: 27588378
DOI: 10.23736/S0026-4970.17.03937-1 -
Turkish Journal of Ophthalmology Dec 2021In this study, we aimed to describe the demographic and clinical findings of children with uveitis at a tertiary pediatric rheumatology and ophthalmology center.
OBJECTIVES
In this study, we aimed to describe the demographic and clinical findings of children with uveitis at a tertiary pediatric rheumatology and ophthalmology center.
MATERIALS AND METHODS
A retrospective cross-sectional study was conducted with 46 patients who were diagnosed with uveitis before the age of 16 years and were followed regularly for at least 6 months between January 2013 and June 2019. Demographic data, uveitis characteristics, underlying diseases, systemic treatment modalities, drug side effects, complications, and surgical intervention were evaluated.
RESULTS
Eighty-three eyes of 46 patients were included in the study. The mean age at diagnosis of uveitis was 9.2±4.5 (1.6-15.6) years, and the mean uveitis follow-up period was 54±41 (6-191) months. Twenty-one patients (45.7%) had uveitis associated with rheumatologic diseases. Juvenile idiopathic arthritis was the most common disease (23.9%). Visual acuity was categorized as moderately impaired in 6 eyes (7.2%), severely impaired in 4 eyes (4.8%), and blindness in 1 eye (1.2%). Methotrexate (87%) was the most frequently used systemic immunosuppressive agent in treatment. Adalimumab (73.9%) was added to treatment in resistant cases. Thirty-five patients (76.1%) had complications in at least 1 eye secondary to uveitis or uveitis treatment. Posterior synechiae (11 eyes, 13.2%) was the most common complication during treatment.
CONCLUSION
In order to preserve visual acuity, pediatric uveitis should be recognized early and especially persistent/chronic cases should be started on effective systemic treatment immediately.
Topics: Adolescent; Arthritis, Juvenile; Child; Cross-Sectional Studies; Follow-Up Studies; Humans; Retrospective Studies; Uveitis
PubMed: 34963262
DOI: 10.4274/tjo.galenos.2021.38585