Pediatric Rheumatology最新文献

Background: Genome-wide association studies (GWAS) have pinpointed a multitude of risk loci associated with Juvenile Idiopathic Arthritis (JIA), but it is challenging to decipher novel plasma proteins. To address this, we applied an integrative omics pipeline to uncover novel proteins associated with JIA risk.

Methods: In this research, we utilized an integrative omics method to identify new plasma proteins associated with JIA. Complementary results from an independent cohort were analyzed through Whole Genome Sequencing (WGS), single-cell RNA sequencing (scRNA-seq), and bulk RNA sequencing (bulk RNA-seq) at the Children's Hospital of Chongqing Medical University to validate the reliability of the identified novel proteins. Additionally, to assess the therapeutic potential of novel proteins, we performed Phe-WAS and conducted an extensive review of existing literature using PubMed and Web of Science.

Results: An integrative omics pipeline analysis identified ERAP2 as having putatively causal effects on JIA. In the fourth step of Summary-data-based Mendelian randomization analysis, we discovered that the SNP rs2927608 and rs2910686 can regulate the expression of the ERAP2 gene, thereby regulating the protein content of both ERAP2 and ERAP1. WGS analysis also detected two potentially pathogenic mutations on ERAP2 in sJIA patients. ScRNA-seq reveals that ERAP2 expression is significantly elevated in patients with sJIA compared to normal and other subtypes, particularly in monocytes. Bulk RNA-seq with ROC analysis demonstrating significant diagnostic power (AUC = 0.86, 95%CI: 0.71-1.00) in discriminating sJIA from healthy controls. Literature and Phe-WAS search revealed that ERAP2 is primarily studied in the context of genetic predisposition to disease and is closely related to autoimmune disorders.

Conclusions: ERAP2 was identified as a candidate associated with JIA, especially sJIA, through integrative omics analysis, indicating its potential role in protein-mediated disease mechanisms and therapeutic targeting.

Background: Although typical findings of familial Mediterranean fever (FMF), such as brief fever episodes and abdominal or chest pain, have been largely described, little is known about the neurological manifestations of the disease in childhood.

Methods: A systematic search of the literature was conducted in PubMed/Medline, Cochrane, and Web of Science databases in accordance with the PRISMA guidelines, using MeSH terms related to FMF and neurological manifestations. Studies involving patients under 18 years of age diagnosed with FMF with neurological manifestations were included.

Results: Sixty-four studies, comprising 4753 children with FMF, were included. Approximately 33.9% of them had some degree of neurological involvement. Headache was the most common neurological symptom and was often associated with FMF flares, with frequencies ranging from 4.8 to 58.8%. Febrile seizures were also relevant manifestations, as expected in children with FMF since they have more and more high fever during childhood, with frequencies ranging from 1 to 15.2%. Demyelinating disorders, such as multiple sclerosis, were rarely reported, mostly in female adolescents with the homozygous M694V MEFV genotype. A few studies have shown that cochlear and retinal involvement due to chronic and recurrent inflammation may contribute to sensorineural hearing loss and retinal abnormalities.

Conclusion: Although causality has not been shown and reporting bias cannot be excluded, neurological involvement appears relatively common in children with FMF and may lead to long-term disability and reduced quality of life. These findings support the need for a comprehensive neurological assessment to enable early detection, appropriate management, and better long-term outcomes.

Background: Accelerated vascular stiffness and myocardial dysfunction in juvenile idiopathic arthritis have been established. However, the relationship between these two conditions remains under investigated in the literature. The aim of this study was to determine whether there is any correlation between the extent of vascular and myocardial involvement in JIA patients.

Methodology: For this purpose, 22 JIA patients and an equivalent number of controls were investigated by flow-mediated dilation (FMD) of the brachial artery and aortic circumferential strain (ACS) for the measurement of vascular function, in addition to 3D speckle tracking echocardiography and global longitudinal strain (GLS) for left ventricular function. The degree of inflammation in JIA patients was estimated via the JADAS-10 score.

Results: Both ACS and FMD were impaired in cases compared with controls (median value in cases 15 vs. 21 in controls); similarly, GLS was significantly reduced in cases (median value 17) compared with controls (22). There was a significant correlation between ACS and GLS, indicating an intimate relationship between both conditions. Impaired vascular relaxibility was associated with increased JADAS scores, suggesting a negative effect of inflammation on accelerated vascular degeneration.

Conclusion: There is currently an increasing body of evidence that cardiovascular disease partly results from low-grade inflammation, and there are also speculations that subtle myocardial dysfunction results from vascular involvement with impaired coronary relaxibility. We believe that this study adds more evidence to the latter. More studies involving more patients, notably at the molecular level, are needed to validate these results and to further understand their mechanisms.

Background: Whilst musculoskeletal ultrasound (MSUS) normal values for examination of the hip joint have been established for healthy children, equivalent values for patients with juvenile idiopathic arthritis (JIA), as well as internationally validated MSUS protocols for the optimal evaluation of synovitis are lacking. This study aimed to develop and validate the most sensitive MSUS protocol for the detection of hip synovitis in JIA.

Methods: In consecutive JIA patients with ≥ 1 clinically affected hip joint, affected and unaffected hips underwent MSUS. Disease, demographic and clinical findings were recorded. Synovitis was graded using the pediatric OMERACT score for B-Mode (BM) and power-Doppler Mode (PD) in the longitudinal and transverse scans and the sensitivity and specificity was analyzed. Additionally anterior recess size (bone to capsula distance), capsula thickness and femoral head cartilage thickness (transverse view) were measured. Published data provided further control data for anterior recess size (children without JIA). Interobserver reliability of BM and PD was tested using Fleiss-Kappa.

Results: 60 patients were enrolled who had 76 hips with and 32 without clinical arthritis. BM was positive (grade ≥ 1) in 74/76 of hips with clinical arthritis (97%, sensitivity 0.97 (0.93-1.0), specificity 0.85 (0.74-0.97) versus 2/32 (6%) in hips without arthritis. PD positivity frequency was 6 (8%) in hips with arthritis versus 0 in hips without. Anterior recess size (mean ± SD) was significantly wider in patients with clinical arthritis (9.9 ± 2.5 vs 5.5 ± 1.3, p-value 0.001). Use of the cut-off of ≥ 7.2 mm resulted in an area under the curve of at least 95%, with a sensitivity of 86% and specificity of 94%. Articular capsula and femoral head cartilage thickness did not differ between patients with and without arthritis. Recess size was comparable in the internal and external control groups (n = 449). Interobserver reliability of BM and PD positivity showed excellent agreement (kappa = 0.85).

Conclusions: The Pediatric internationally agreed UltraSound hip synovitis protocol (PIUS-hip) could be limited to one longitudinal scan including B-Mode scoring plus measurement of anterior recess size for maximal sensitivity and specificity for synovitis.

Background: Lupus nephritis (LN) is a significant cause of morbidity and mortality in pediatric systemic lupus erythematosus (SLE), with more severe disease seen in childhood-onset cases. In low-to-middle-income countries like the Philippines, financial barriers and healthcare limitations exacerbate poor outcomes. This study aims to describe the clinical features, prognostic factors, and outcomes of childhood-onset LN at the Philippine General Hospital.

Methods: A retrospective cohort study was conducted on patients under 19 years diagnosed with LN from January 2014 to December 2021. Clinical, laboratory, treatment, and outcome data were extracted from medical records. Survival was estimated using the Kaplan-Meier method. Cox proportional hazards regression and logistic regression were used to identify predictors of mortality and progression to chronic kidney disease 5 (CKD 5), respectively.

Results: A total of 128 patients were included, with a mean age of 14.4 years at LN diagnosis and a female-to-male ratio of 13.2:1. Only 16% underwent kidney biopsy, mainly due to financial constraints. Treatment delays and poor adherence occurred in 60% and 38% of patients, respectively, largely due to financial hardship and limited healthcare access. The median follow-up was 2.2 years (range, 0.0-8.8 years). Nephrotic range proteinuria (hazard ratio [HR] 2.91), hypertension at diagnosis (odds ratio [OR] 5.57), and failure to achieve early partial response or complete remission (HR 3.69) were significant predictors of poor health outcomes. Twenty five patients (19.5%) died during the observation period with infection as the leading cause of mortality.

Conclusions: Childhood-onset LN remains associated with high morbidity and mortality in the Philippines, highlighting the urgent need for early diagnosis, expanded diagnostic access, infection risk mitigation, early therapeutic response monitoring, and strategies to enhance treatment adherence to improve outcomes.

Background: The ChRonic nonbacterial Osteomyelitis Magnetic Resonance Imaging Scoring (CROMRIS) tool was developed to assess specific characteristics of bone and soft tissue inflammation on MR images of patients with CNO; however, this tool was labor intensive to utilize. We aimed (1) to refine and adapt this scoring method, (2) to assess the usability of this web-based CROMRIS system among radiologists and (3) to evaluate the absolute agreement of the components and summary CROMRIS scores at each body site, and the interrater reliability.

Methods: We used a qualitative, user-centered design approach involving software developers, rheumatologists, radiologists, and a patient artist to adapt the paper-based scoring system to a web-based prototype that was further refined by monthly meetings between the group members. A clickable-schematic-based CROMRIS system was developed to include all body regions: head (skull/mandible), spine, torso (clavicle, sternum, and ribs), pelvis, hands, feet, arms, and legs. Readers scored individual bone units to indicate the presence of bone marrow hyperintensity on STIR images (score 0-1), soft tissue/periosteal hyperintensity of surrounding tissue (score 0-1), and bony expansion (score 0-1), and quantified the signal size of the CNO lesion (scores 1-3 defined as < 25%, 25-50%, or > 50% of the estimated volume, respectively). The sum of these parameters for lesions detected on fluid-sensitive sequences was the CROMIS Activity Index (maximum score 720). Feedback for usability was reported with descriptive content analysis and continuous variables as means and categorical variables as percentages. Interrater reliability was assessed by free-marginal kappa (k) statistics and the intraclass correlation coefficient (ICC).

Results: The mean system usability score increased from 64.5 (below average) to 75 (above average) after user feedback. Interrater reliability for the CROMRIS Activity Index was excellent for clavicle, tibia, cervical and lumbar spines (> 0.9) and good to moderate for the remainder of the body regions. The mean kappa of each category of bones was > 0.6 demonstrating substantial interrater reliability among radiologists for the bone sites most affected by CNO, namely the long bones and clavicle.

Conclusion: The web-based CROMRIS portal developed was usable and showed substantial-moderate agreement in the total CROMRIS Activity Index total scores among experienced radiologists after self-guided learning of the atlas and video. This tool can potentially be used in future clinical trials after calibration.

Background: Telemedicine has improved access to pediatric rheumatology care. A disadvantage to using virtual modality for evaluation of children with arthritis is the lack of an in-person, hands-on physical exam. Thermal imaging has been studied in the clinical setting with promising results. This study aims to determine the feasibility of procuring at-home thermal imaging, measuring the variability of in-home skin temperature measurements over three consecutive days, and to compare these measurements at home to ones obtained in the clinic setting.

Methods: Children with knee pain and/or swelling for a week or longer were enrolled and imaged with a smartphone-attached FLIR ONE PRO and Fluke handheld cameras followed by imaging with a FLIR camera at home for 3 consecutive days. Joint exam performed in the office was used as gold standard for joint assessment. A previously validated metric of temperature after within-limb calibration (TAWiC), defined as the temperature differences between the knee joint and ipsilateral mid-tibia, was used for all imaging studies.

Results: Fifty-three patients were enrolled and thirty-eight completed the imaging acquisition at home with analyzable images. When evaluating images of the knee and mid-tibia regions, images collected at home compared to in-office demonstrated consistently lower absolute temperatures. However, the calibrated temperatures (TAWiC) of the anterior and lateral views of the knee showed mild to moderate correlation across 3 days between home-acquired images and office-acquired images (r = 0.58, 0.26, 0.24 and r = 0.36, 0.41, 0.42, respectively). The sensitivity and specificity of detecting arthritis of the knee using TAWiC adjustments from previously defined thresholds were similar regardless of the setting of image acquisition (0.44 and 0.79).

Conclusions: This study demonstrates the feasibility of applying TAWiC for arthritis detection through a smartphone-based infrared thermal camera operated by families at home. Further investigation on a larger scale is needed prior to implementation of this process in the telemedicine setting.