Rheum for earlier recognition: patient reported time to diagnosis of juvenile idiopathic arthritis.

Objective To investigate the clinical significance of serum anti-cyclic citrullinated peptide(anti-CCP) antibodies in diagnosis of juvenile idiopathic arthritis(JIA). Methods Serum anti-CCP antibodies of 68 children suspected of JIA with fever and arthritis of unknown causes were determined by ELISA,and comprehensive analysis was carried out with clinical data and related laboratory findings. Results Among the 68 children suspected of JIA,there were 10 cases of polyarticular JIA,13 cases of systemic onset JIA,8 cases of oligoarticular JIA and 13 cases of enthesitis related JIA.There were 11 cases of other rheumatoid diseases,8 cases of neoplastic diseases of blood and 5 cases of infectious diseases.The serum anti-CCP level in children suspected of polyarticular JIA was significantly higher than those in children suspected of systemic onset JIA,oligoarticular JIA and enthesitis related JIA(P0.05).With serum anti-CCP ≥15.8 RU/mL as the positive threshold value,the area under receiver operating characteristic curve was 0.80,and the sensitivity and specificity in diagnosis of polyarticular JIA were 80% and 67.6% respectively.The serum anti-CCP level was positively related to serum C-reaction protein level in children suspected of polyarticular JIA(r=0.764,P=0.017). Conclusion Serum anti-CCP can be used for the diagnosis of polyarticular JIA,and 15.8 RU/mL may be a suitable cut-off level.

THU0498 The Patients' Experience of Imaging: Views from a Group Convened to Support the Development of Points to Consider for the Use of Imaging in the Diagnosis and Management of...

Background Temporomandibular joint (TMJ) arthritis is common in children with juvenile idiopathic arthritis (JIA), but often clinically asymptomatic. Magnetic resonance imaging (MRI) is the most reliable examination method, but requires sedation in young children. The aim of our study was to evaluate whether early TMJ MRI will change the treatment of patients with newly diagnosed JIA. Methods Single center chart review of all patients with a diagnosis of JIA between January 2007 and December 2010. Results We found 147 patients with newly diagnosed JIA during this period. In 111 (76%) at least 1 MRI of the TMJ was available. Reasons why no TMJ MRI was done were parents’ refusal (10), MRI of other locations (7), fixed dental appliances (16) and unclear cause (3). A diagnosis of TMJ arthritis based on increased joint enhancement on MRI was made in 91/111 (82%) patients. The first MRI was done at a median interval of 5 months from the diagnosis of JIA, and 61/111 patients (55%) required sedation for their first MRI. TMJ arthritis was diagnosed in 53/61 (87%) requiring sedation and in 34/50 (68%) patients without sedation (p = 0.003). Following the first TMJ MRI, intra-articular steroid injections were performed into 107 TMJs of 60 patients. 48/147 (33%) patients received at least one DMARD to control their disease, and in 9/48 (19%) the first DMARD was started following the first TMJ MRI. Factors associated with TMJ involvement as demonstrated by MRI were JIA subtype (p = 0.007) and a younger age at diagnosis of JIA (p = 0.04). Conclusion In our cohort of newly diagnosed JIA patients TMJ arthritis was very common. Early TMJ MRI led to changes in treatment in 62% of patients with additional joint injections in 60 patients and start of systemic medication in 9 patients. We especially recommend performing TMJ MRI in young children even if they require sedation, as they have an increased rate of TMJ involvement.

AB0740 IMPACT OF DIAGNOSIS DELAY ON DISEASE PARAMETERS DURING JUVENILE IDIOPATHIC ARTHRITIS

BACKGROUND: Juvenile idiopathic arthritis is the most common chronic inflammatory musculoskeletal disease in children. Its most prevalent clinical subtype is oligoarthritis. Pigmented villonodular synovitis, also known as tenosynovial giant cell tumor, is a rare benign synovial disorder, which may clinically resemble oligoarthritis. Differential diagnosis between juvenile idiopathic arthritis and pigmented villonodular synovitis is challenging. Intra-articular steroids used in juvenile idiopathic arthritis therapy may induce negative effects in patients with pigmented villonodular synovitis. Orthopedic and surgical procedures used to rule out pigmented villonodular synovitis are burdensome for children. Magnetic resonance imaging may yield similar findings for both conditions at early stages. Several studies revealed that serum calprotectin is a promising biomarker for juvenile idiopathic arthritis. AIM: To assess synovial fluid calprotectin concentrations in children with oligoarthritis and pigmented villonodular synovitis. METHODS: The synovial fluid concentrations of calprotectin, interleukin-6, and tumor necrosis factor-alpha in 42 children with oligoarthritis and 12 children with diffuse pigmented villonodular synovitis of the knee joint were obtained by enzyme-linked immunosorbent assay. In patients with juvenile idiopathic arthritis, cytokine levels were determined at disease onset, and prior to therapeutic and diagnostic arthroscopy in those with pigmented villonodular synovitis. RESULTS: Synovial calprotectin significantly increased in children with oligoarthritis (108 [28.2; 237] μg/mL) compared to those with pigmented villonodular synovitis (1.53 [1.26; 1.69] μg/mL; p 0.001). No statistically significant differences were found in synovial tumor necrosis factor-alpha and interleukin-6 concentrations between patients with juvenile idiopathic arthritis and those with pigmented villonodular synovitis. ROC analysis showed a synovial calprotectin threshold of 2.9 μg/mL for the diagnosis of juvenile idiopathic arthritis (AUC = 0.996 ± 0.00479; 95% CI: 0.926–1.000). CONCLUSION: In children, the differential diagnosis of oligoarthritis is often complicated by clinically similar nonrheumatic joint disorders. The main synovial proinflammatory markers cannot be used for the differential diagnosis of juvenile idiopathic arthritis and pigmented villonodular synovitis. Synovial calprotectin concentration is a promising biomarker of juvenile idiopathic arthritis.

Temporomandibular joint (TMJ) arthritis is common in children with juvenile idiopathic arthritis (JIA), but often clinically asymptomatic. Magnetic resonance imaging (MRI) is the most reliable examination method, but requires sedation in young children. The aim of our study was to evaluate whether early TMJ MRI will change the treatment of patients with newly diagnosed JIA. Single center chart review of all patients with a diagnosis of JIA between January 2007 and December 2010. We found 147 patients with newly diagnosed JIA during this period. In 111 (76%) at least 1 MRI of the TMJ was available. Reasons why no TMJ MRI was done were parents’ refusal (10), MRI of other locations (7), fixed dental appliances (16) and unclear cause (3). A diagnosis of TMJ arthritis based on increased joint enhancement on MRI was made in 91/111 (82%) patients. The first MRI was done at a median interval of 5 months from the diagnosis of JIA, and 61/111 patients (55%) required sedation for their first MRI. TMJ arthritis was diagnosed in 53/61 (87%) requiring sedation and in 34/50 (68%) patients without sedation (p = 0.003). Following the first TMJ MRI, intra-articular steroid injections were performed into 107 TMJs of 60 patients. 48/147 (33%) patients received at least one DMARD to control their disease, and in 9/48 (19%) the first DMARD was started following the first TMJ MRI. Factors associated with TMJ involvement as demonstrated by MRI were JIA subtype (p = 0.007) and a younger age at diagnosis of JIA (p = 0.04). In our cohort of newly diagnosed JIA patients TMJ arthritis was very common. Early TMJ MRI led to changes in treatment in 62% of patients with additional joint injections in 60 patients and start of systemic medication in 9 patients. We especially recommend performing TMJ MRI in young children even if they require sedation, as they have an increased rate of TMJ involvement.

Objective: To examine and delineate inflammatory focus in patients with juvenile idiopathic arthritis (JIA), 18F-Fluoro-deoxy-glucose (FDG)-positron emission tomography (PET) (18F-FDG-PET) was applied to patients with JIA, and the images of these patients were compared.Methods: Sixty-eight children (59 with systemic JIA (s-JIA) and 9 with polyarticular JIA) were included. The diagnosis of JIA was done to meet the International League of Associations for Rheumatology (ILAR) criteria. After 6-h fasting, whole-body positron emission tomography (PET) scans were acquired 60 min after intravenous injection of 3–5 MBq/kg 18F-FDG. The interpretation of 18F-FDG uptake was based on visual characteristics.Results: Two types of PET images were outstanding in s-JIA; one was 18F-FDG uptake in red bone marrow, such as the spine, pelvis, and long bones as well as spleen (12 cases), and other type was the uptake in the major joints, such as hips, elbows, wrists, knees, and ankles (8 cases). The former findings were correlated with elevated levels of inflammatory markers, while the latter were with significantly increased levels of MMP-3 (p < 0.05).Conclusion: There was a noticeable accumulation of 18F-FDG uptake in bone marrow of s-JIA patients which may indicate the inflammatory focus of this disease and play an important role in the pathogenic basis of arthritis and systemic inflammation of s-JIA.

Introduction. Juvenile idiopathic arthritis (JIA) is a common multifactorial disease characterized by the presence of chronic inflammation in the joints, entheses and other structures of the musculoskeletal system in combination with a certain range of extraskeletal disorders. Vast variety of JIA clinical variants and the variability of the disease course make primary and differential diagnosis difficult, which often leads to a delayed start of treatment and an inadequate choice of medical therapy or, conversely, an excess of medication. In the range of differential diagnostic conditions that have similar symptoms and are manifested by severe arthralgia, gait disturbance, joint stiffness, as well as the presence of effusion and gradual progression of bone destruction mainly in the epiphyseal plate, one should remember about hereditary skeletal dysplasias, primarily from a genetically heterogeneous group of multiple epiphyseal dysplasias (MED). The aim of the study – description of the clinical and genetic characteristics of three patients with various genetic variants of MED and defining approaches for their differential diagnosis with JIA. Materials and methods. There were three patients from three unrelated families aged from 7 to 13 years old under our supervision. To clarify the diagnosis, a genealogical analysis, a clinical examination of patients and first-degree relatives, as well as an assessment of X-ray images of long tubular bones were carried out. Molecular genetic confirmation of the MED diagnosis types 1 and 2 was based on the results of custom panel sequencing consisting of 166 genes responsible for the development of hereditary skeletal pathology. To clarify the molecular genetic diagnosis of MED type 4, an analysis of the SLC26A2 gene was performed using automated Sanger sequencing. Results. Anamnestic, clinical, radiological, and molecular genetic characteristics of three unrelated patients with different genetic types of MED caused by variants in the COMP, SLC26A2, and COL9A2 genes were analyzed. The first symptoms of the disease in observed patients with three different genetic variants of MED occurred at the age of 2–3 years old and were characterized by gait disturbance and climbing stairs difficulties. Gradually, these symptoms were accompanied by pain in large joints. According to the ultrasound examination of the joints, signs of synovitis were noted, as a result they were diagnosed with JIA (polyarticular variant, seronegative for rheumatoid and antinuclear factor) and immunosuppressive therapy were prescribed without significant effect. The atypical course of the JIA was the reason for additional examination of patients by an orthopedist and geneticist. Careful analysis of the large joints radiographs made it possible to suspect one of the variants of MED in our patients based on the detection of distinctive signs, which were characterized by abnormal ossification (diminished size and flattening) of the epiphyses and abnormal shape and structure of the femoral head epiphysis. Molecular genetic analysis was performed to confirm the diagnosis. As a result, a pathogenic variant of the nucleotide sequence in the COMP gene was detected in one of the patients, two pathogenic variants in the SLC26A2 gene in another patient, and one pathogenic variant in the COL9A2 gene in the third patient, which made it possible to confirm the final diagnosis of MED type 1 with an autosomal dominant type of inheritance, MED type 4 with an autosomal recessive type of inheritance and MED type 2 with an autosomal dominant type of inheritance, respectively. Based on the results of our own research and analysis of the literature data, key directions for the differential diagnosis of MED and JIA were formulated. It is shown that the analysis of the X-ray images of patients is essential in differential diagnosis. Conclusion. Despite the significant overlap of the clinical symptoms between JIA and MED, the key to the early diagnosis of MED is a comprehensive examination, which included genealogical analysis, features of clinical manifestations and disease course in combination with distinctive radiological signs including delayed ossification of the epiphyses of tubular bones typical for MED. However, the question remains about the probability of a combined nature of osteoarticular disorders, i. e., the possible development of JIA in patients with hereditary skeletal dysplasias which requires in-depth study in the future.

Little is known about the rates of rheumatic disease diagnosis among children during the COVID-19 pandemic. We examined the impact of the pandemic on the diagnosis of juvenile idiopathic arthritis (JIA) in the United States. We performed a historical cohort study using US commercial insurance data (2016-2021) to identify children aged <18 years without prior JIA diagnosis or treatment in the prior ≥12 months. New JIA diagnoses were identified using a combination of ICD-10-CM diagnosis codes, location, and timing of medical services. Crude rates with 95% confidence intervals (CIs) of JIA diagnosis per 100,000 enrolled children per quarter were estimated and stratified by age group, sex, region, JIA type, and uveitis. The incidence rate ratio (95% CI) for JIA diagnosis was estimated using Poisson regression, adjusted for various demographic variables. From 2018-2021, 643 children were diagnosed with JIA. Crude new JIA diagnoses per 100,000 children per quarter dropped from 2.62 (95% CI, 2.39-2.87) prepandemic to 1.94 (95% CI, 1.66-2.25) during the pandemic. Declines in JIA diagnosis were more apparent in the US Northeast and West regions and among children aged 6-11 years. After adjustment for covariates, JIA diagnoses fell by 30% during the pandemic compared with the prior 3 years (IRR, 0.70; 95% CI, 0.59-0.83). Compared with the prepandemic period, JIA was diagnosed 30% less often during the early pandemic among commercially insured children in the United States. More research is needed to understand the underlying reasons for these changes in JIA diagnosis and more recent trends.

To evaluate exposure to environmental factors inhaled during pregnancy and after birth until juvenile idiopathic arthritis (JIA) diagnosis among residents of a large city. This is an exploratory case-control study that consists of 66 patients with JIA and 124 healthy controls matched by age and sex, living in the São Paulo, Brazil, metropolitan area until JIA diagnosis, and whose mothers had resided in this region during pregnancy. A structured and reliable questionnaire (κ index for test-retest was 0.80) assessed demographic data, gestational and perinatal-related factors, and exposure to inhalable environmental elements during pregnancy and after birth (occupational exposure to inhalable particles and/or volatile vapor, exposure to cigarette smoke, and the presence of industrial activities or gas stations near the home, work, daycare, or school). Tropospheric pollutants included particulate matter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), and carbon monoxide (CO). During pregnancy, intrauterine cigarette smoke exposure (OR 3.43, 95% CI 1.45-8.12, p = 0.005) and maternal occupational exposure (OR 13.69, 95% CI 4.4-42.3, p < 0.001) were significant independent risk factors for JIA diagnosis. In contrast, maternal employment (OR 0.06, 95% CI 0.02-0.2, p < 0.001) and ideal maternal weight gain (OR 0.36, 95% CI 0.2-0.8, p = 0.017) presented negative associations. Secondhand smoke exposure from birth to JIA diagnosis (OR 3.6, 95% CI 1.8-7.3, p < 0.001) and exposure to O3 during the second year of life (OR 2.76, 95% CI 1.20-6.37, p = 0.017) were independent and significant risk factors for the pathogenesis of JIA. In our study, cigarette smoke exposure (intrauterine and after birth), exposure to O3 in the second year of life, and maternal occupational exposure were identified as potential risk factors for JIA, warranting further study.

BackgroundBiomarker search for juvenile idiopathic arthritis (JIA) diagnosis and monitoring remain the focus of research worldwide. Several microRNAs (miRNAs) have been identified as relevant in different rheumatic conditions; however, studies in JIA remain limited. Our study aimed to explore the potential of serum and urine-derived miRNAs for JIA diagnostics and longitudinal JIA monitoring.MethodsIn this single-center, prospective study, three selected miRNAs (miR-16, -146a and -155) were tested in serial serum and urine samples collected from 31 JIA patients and 22 healthy controls (HC) via quantitative reverse transcription polymerase chain reaction (RT‒qPCR). The diagnostic performance of variables for distinguishing JIA patients from HCs was assessed by determining the area under the receiver operating characteristic (ROC) curve (AUC). The prediction of remission was evaluated using Cox regression and Kaplan-Meier analyses. A p-value < 0.05 was considered statistically significant.ResultsLower miR-16 and higher miR-155 levels were detected in serum of JIA patients’ vs. HC (p < 0.01), whereas the level of miR-146a was lower in urine of JIA patients (p = 0.032). In ROC analysis, miR-16 and miR-155 distinguished JIA patients from HC when analyzed in serum (AUC 0.81, 95% CI 0.70–0.93, p < 0.001 and AUC 0.73, 95% CI 0.59–0.87, p = 0.005, respectively), and miR-146a– in urine (AUC 0.68, 95% CI 0.53–0.82, p = 0.030). During 12 months follow-up period increasing miR-16 (p = 0.021) and decreasing miR-155 (p = 0.009) levels were observed in serum samples. Kaplan-Meier survival analysis revealed that a high level of miR-146a in serum significantly predicts JIA remission (HR = 2.2, 95% CI 0.7–6.9, p = 0.040).ConclusionsThis study highlights the utility of miRNAs in JIA diagnosis, monitoring and prognosis and demonstrates the feasibility of using urine as a noninvasive source of miRNAs in children with non-systemic JIA.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12969-025-01136-w.

Funding sources: None. IRB approval status: This study was exempted from review by the IRB (Ethical committee of Northern Ostrobothnia Hospital District) since it was a registry-based study.

OBJECTIVE:Juvenile idiopathic arthritis (JIA) is the most common cause of chronic arthritis in children. Biologics have changed the faith of children with rheumatic diseases. The main objective of this study was to demonstrate the rate of usage, efficacy and safety of biologics in JIA subtypes.METHODS:This retrospective observational cohort study was conducted between May 2010 and September 2017. All children with the diagnosis of JIA and children under a biological agent treatment were recorded into the local registry system. Age, gender, JIA subtype, medications used, the clinical status of the patient, tuberculosis screening results, and side effects observed under biologics were retrieved from the registry.RESULTS:There were 405 patients with the diagnosis of JIA in the cohort. Biologics were used in 123 (30.3%) JIA patients. Subtype frequencies of JIA patients were as follows: persistent oligoarticular JIA (33.6%), enthesitis-related arthritis (29.2%), systemic JIA (13%), rheumatoid factor (RF)-negative polyarticular JIA (13%), extended oligoarticular JIA (4.2%), RF-positive polyarticular JIA (3.4%), psoriatic arthritis (1.8%) and unclassified arthritis (1.8%). The rate of biologic use was high in extended oligoarticular JIA (64.7% of the cases), RF-positive polyarticular JIA (57.1%), psoriatic arthritis (57.1%), RF-negative polyarticular JIA (41.5%), and in systemic JIA (39.6%). Enthesitis-related arthritis (27.1%), persistent oligoarticular JIA (17.6%) and unclassified arthritis (16.6%) patients were the cases that needed a biologic agent in the last order. At the last control, 78.9% of the cases were in remission, while 21.1% of them were active despite biologic treatment. Isoniazid prophylaxis was used in 30.8% of the patients. None of the patients developed active tuberculosis infection under prophylaxis. Adverse events were observed in 18.6% of patients under biologics as recurrent uncomplicated upper respiratory tract infections being the most common.CONCLUSION:Biologics are safe and effective treatment options in children with JIA. Most of the JIA patients with polyarticular involvement require biologics earlier in the disease course. The risk of tuberculosis infection seems not to be increased after appropriate screening and prophylaxis.

The current role of conventional radiography in the diagnosis, monitoring and prognosis of juvenile idiopathic arthritis (JIA)is reviewed, as its role has changed with the increasing use of ultrasound and magnetic resonance imaging, as well as with the introduction of biological drugs. Conventional radiography does not play an important role in the diagnosis of JIA, as this is based on history, clinical examination and laboratory findings. The main role of conventional radiography is in the detection and monitoring of growth disorders and chronic structural and morphological changes of the affected joints and bones, in addition to helping with the differential diagnosis of conditions that mimic JIA. Radiographic changes of the joints depend on the age of the child, the type and duration of arthritis and the specific joints affected. There are no standard protocols for arthritis monitoring and most indications for imaging are based on individual case-by-case decisions. The development of degenerative joint changes is considered a poor predictive factor, but there are no clear studies that more precisely define the predictive valueof radiographic changes. Conventional radiography remains an important imaging modality in narrowing the differential diagnosisand in evaluating growth disorders and the developing destructive joint changes.

BACKGROUND AND PURPOSE:Juvenile idiopathic arthritis (JIA) is the most common type of arthritis in children. JIA patients are at risk of developing uveitis and undergo ophthalmic screening at specific regular intervals based on international JIA screening guidelines. This study aimed to assess the adherence of ophthalmology and rheumatology services, and patients followed at Sultan Qaboos University Hospital (SQUH), Oman, to the screening guidelines and identify factors influencing adherence.SUBJECTS AND METHODS:In this retrospective cohort study, we reviewed the charts of all patients diagnosed with JIA from 2015 to 2020 who were followed up by the pediatric rheumatology service at SQUH. Data collected included the patient’s demographics, age at diagnosis of JIA and age at diagnosis of uveitis, disease duration, JIA subtype, disease markers, treatment, and frequency of rheumatology and ophthalmology appointments. The patients’ actual appointments were compared with their planned appointments to assess adherence to the screening schedule.RESULTS:Thirty-nine JIA patients (13 males, 26 females) were recruited in the study. The median age of the patients at diagnosis of JIA was 3 years (interquartile range 2–7 years). The distribution of JIA subtypes was 13 (33.3%) oligoarticular JIA patients, 14 (35.9%) systemic-onset JIA patients, and 12 (30.8%) polyarticular JIA patients. A total of 23 (59%) patients were on biologics. Rheumatology service adherence for referring for the first screening visit was 94.9%, while ophthalmology adherence for scheduling first-visit appointments was 76.9%, and patient adherence for the first visit was 96.7%. Over the 5 years, the average adherence to screening guidelines was 81.3% for the ophthalmology service and 88.4% for patients. One patient developed uveitis during the study period. A significant association was found between higher age at diagnosis of JIA patients and patient adherence (P = 0.037). A significant association was also found between shorter JIA disease duration and patient adherence (P = 0.000275).CONCLUSION:Assessment of adherence to the JIA screening recommendations for uveitis at SQUH revealed some shortcomings. While the rheumatology service’s adherence is good, the ophthalmology service’s adherence needs improvement. Patients’ adherence to the first visit appointment is optimal but needs improvement throughout the 5 years. Although all patients had risk factors for uveitis, only one developed uveitis. In this cohort study of Omani JIA patients, the occurrence of uveitis seems to be low.