Pediatric Rheumatology最新文献

Background: Enthesitis-related arthritis (ERA) may exhibit a distinct disease spectrum on the basis of ethnic origin. The pediatric rheumatology teams from the Istanbul Medical Faculty and Tunisia Kassab Institute engaged in collaboration via the Second Sister Hospital Initiative of the European Society of Pediatric Rheumatology (PReS) to investigate the clinical characteristics and outcomes of children with ERA.

Methods: The medical records of patients with the diagnosis of ERA were reviewed retrospectively. The Juvenile Spondyloarthritis Disease Activity Index (JSpADA) was the tool for assessing disease activity. In addition to clinical and laboratory findings, treatments and disease outcomes were compared.

Results: A total of 94 children with ERA were enrolled (45 Tunisian, 49 Turkish). Sex and age at disease onset were similar between the groups. Heel pain (8.8% vs. 61.2% for Tunisia vs. Türkiye, p = 0.03) and enthesitis (40% vs. 69.3% for Tunisia vs. Türkiye, p = 0.03, p = 0.8) were more common in Turkish children. Conversely, the rates of sacroiliac tenderness, suggesting clinical sacroiliitis (91.1% vs. 55.1% for Tunisia vs. Türkiye), and axial disease (97.8% vs. 55.1% for Tunisia vs. Türkiye) were significantly greater in Tunisian children (p = 0.002 and p < 0.001, respectively). Overall, 45.7% of the cohort was HLA-B27 positive, including 32% of Turkish patients and 60% of Tunisian patients (p < 0.001). HLA-B27 positivity did not influence age at disease onset (p = 0.45) but was associated with a longer diagnostic delay of the disease (p < 0.001). Nearly half of the Turkish children received biologics during the disease course, whereas only 8.9% of the Tunisian children did. While the median JSpADA scores at disease onset were similar between the groups, Turkish patients had significantly lower scores at the last visit than Tunisian patients did (p < 0.001).

Conclusions: This study highlights notable differences in the clinical features and outcomes of ERA among Turkish and Tunisian children, emphasizing the potential influence of ethnic and regional factors on disease presentation and management. Variations in HLA-B27 positivity and treatment approaches, including the use of biologics, further underscore the need for tailored strategies in managing ERA across diverse populations.

Aims: The goal of this systematic review and meta-analysis was to provide references for future researchers on how to develop and implement predictive models for renal injury in paediatric IgA vasculitis (IgAV).

Design: Systematic review and meta-analysis of observational studies.

Methods: We systematically searched databases including China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science and Technology Journal Database (VIP), SinoMed, PubMed, Web of Science, Cochrane Library, and Embase for studies on the construction of predictive models for renal injury in children with IgAV, up until 24 November 2024. Two researchers independently screened the studies, extracted data, and assessed bias risk via the Prediction Model Risk of Bias Assessment Tool (PROBAST). STATA 16.0 software was used to conduct meta-analysis of the area under the curve (AUC) values of the models.

Results: A total of 1,157 studies were retrieved. And 11 studies met the inclusion criteria. The sample sizes ranged from 155 to 583, with a renal injury incidence of 26.7-63.8%. The most common predictors included age, recurrent or persistent purpura, immunoglobulin A (IgA), D-dimer, and serum albumin (ALB). The included studies showed good overall applicability, however all were highly biased, mainly because they used inadequate data sources and reported poorly in the area analyzed. The pooled AUC of the five models was 0.86 (95% CI: 0.80-0.92), demonstrating good predictive power.

Conclusion: In spite of the fact that the renal injury prediction model was found to be somewhat predictive in children with IgAV, all of them had a high risk of bias according to the PROBAST checklist. For these predictive tools to be more robust and clinically applicable, new models with larger sample sizes, rigorous designs, and external validation should be developed in the future.

Background: Biomarker 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.

Methods: In 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.

Results: Lower 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).

Conclusions: This 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.

Background: Mevalonate kinase deficiency (MKD) is a rare autoinflammatory disease, and mevalonic aciduria (MA) is a severe phenotype of MKD. The present study reports the characteristics of MKD and four novel mutations in the mevalonate kinase (MVK) gene in a Chinese cohort.

Method: A retrospective study was conducted on patients diagnosed with MKD from July 2013 to December 2024. The clinical, immunological, and follow-up data were collected from electronic medical records. Next-generation sequencing and Sanger sequencing were performed to identify gene mutations. A literature review was performed on MKD patients to further investigate the associations between genotype and phenotype.

Results: Eleven MKD patients were enrolled from a Chinese cohort of prolonged and recurrent fever of unknown origin. Ten patients were classified as having hyperimmunoglobulin D syndrome (HIDS), and one patient was classified as having MA. The median follow-up duration was 5 years (IQR: 1.5-6 years). Recurrent fever and gastrointestinal symptoms were the most common symptoms. Anemia was observed in 8 of the 11 patients, including one patient with severe hematological complications. Growth restriction (5/11 patients) and developmental delay (4/11 patients) were also observed. IgD levels were measured in ten patients, and the median IgD level was 85.23 µg/ml (IQR: 18.74-385.19 µg/ml). Four novel mutation sites in the MVK gene were discovered: c.78G > A, c.463G > A, c.1076C > T and c.1088G > A. Etanercept was the effective biological agent tested, leading to complete or partial remission in 5 of the 6 patients. A literature review of 20 MA patients suggested that homozygous MVK gene mutations are more frequently associated with MA. Moreover, MA patients with the homozygous A334T mutation present a milder phenotype, and those with the I268T homozygous mutation present a more severe phenotype.

Conclusions: This study is the largest case series of MKD pediatric patients from China. Four new mutation sites in MVK were identified, further expanding the phenotypic and genotypic spectrum of MKD and emphasizing the significance of MVK mutation patterns in influencing disease severity.

Objective: To account for the chronic time course of juvenile idiopathic arthritis (JIA), we assessed medication changes by disease activity patterns across 2 sequential timepoints.

Methods: Patients with non-systemic JIA enrolled in the Childhood Arthritis and Rheumatology Research Alliance Registry with complete clinical Juvenile Arthritis Disease Activity Scores (cJADAS) at 6 and 12-month registry visits were included. Disease activity was classified by cJADAS categories (inactive/minimal, moderate/high). The primary outcome was disease modifying anti-rheumatic drug (DMARD) escalation at the 12-month visit. We examined the association between cJADAS patterns and DMARD escalation.

Results: The cJADAS patterns across paired visits for 2,956 patients with JIA were: 71% persistent inactive/minimal, 25% persistent moderate/high, 2% "improving", and 2% "flaring". Only 10% of patients had DMARD escalation at the 12-month visit, including only 15% of patients with persistent moderate/high disease activity. In multivariable logistic regression adjusting for sociodemographic and clinical variables, DMARD escalation at the 12-month visit was associated with "flaring" disease activity (odds ratio [OR] 2.62, 95% confidence interval [CI] 1.33-5.18), DMARD escalation between the 6- and 12-month visits (OR 1.86, 95% CI 1.40-2.49) and morning stiffness (> 60 min 4.98, 95% CI 3.00-8.27), while age 15-19 years were less likely to escalate (OR 0.61, 95% CI 0.38-0.97).

Conclusion: In a large multicenter registry of US patients with JIA, DMARD escalation at the 12-month visit was uncommon overall, even for those with persistent moderate/high disease activity. Our findings suggest that DMARD escalation in this cohort did not align well with a treat to target approach using cJADAS thresholds.

Objectives: Rheumatoid factor (RF) binds to the immunoglobulin Fc portion, which might influence the efficacy of Fc-carrying TNF inhibitors (TNFi). This has been shown in studies in adults with RF-positive RA, but not yet in children. The aim of this study was to determine efficacy of TNFi in children with seropositive polyarthritis according to rheumatoid factor levels.

Methods: Two databases were searched for patients with JIA/seropositive polyarthritis, admitted between November 2009 and March 2023. Data collected were demographic data, treatment with antirheumatic medications and JADAS27 and cJADAS27 prior to and after start of TNFi treatment. Changes in JADAS27 and cJADAS27 on TNFi were compared between patients with highly elevated RF (> 160 U/ml) and low titre RF (< 160 U/ml) using repeated measures ANOVA.

Results: 28 patients were included, 16 with RF < 160 U/ml at diagnosis, and 12 with RF ≥ 160 U/ml. 21 patients (75%) were treated with etanercept, three (11%) with adalimumab and four (14%) with golimumab, 23 patients additionally received methotrexate. Mean JADAS27 (cJADAS27) at treatment start was 23.0 ± 14.7 (21.0 ± 12.1), and 4.8 ± 5.0 (4.8 ± 4.7) at assessment after starting TNFi. Independent-samples t-test comparing percentage improvement as well as an ANCOVA determined that mean JADAS27 and cJADAS27 scores did not differ significantly across the two time points.

Conclusions: Unlike in adults, efficacy of TNFi was not diminished by elevated levels of RF in this cohort of pediatric patients with seropositive polyarthritis. Further studies are necessary to confirm these findings.

Objective: Juvenile dermatomyositis (JDM) is an uncommon autoimmune condition in children, often leading to prolonged disease burden and significant morbidity. Despite global advancements in understanding JDM, studies from the Middle East, particularly Oman, remain scarce. This study aims to characterize JDM from an Omani national cohort, evaluating clinical manifestations, laboratory features, disease course, and treatment outcomes.

Methods: A retrospective review of all JDM patients diagnosed and managed by pediatric rheumatologist in tertiary centers in Oman was conducted. Patient demographics, clinical features, laboratory findings, treatment modalities, and disease outcomes were analyzed.

Results: A total of 30 children diagnosed with JDM were included. They had an equal female to male distribution, 1:1 ratio. The median age at disease onset was 6.78 years (range: 2-13), with a median diagnostic delay of 8.4 months (range:1-23). The median follow-up period for these patients was 4 years (absolute range: 1 month-16 years). Classic JDM skin manifestations, including heliotrope rash (n = 25; 83%) and Gottron's papules (n = 23; 77%), were common. Proximal muscle weakness was observed in 28 (93%) patients, while 23 (77%) patients exhibited elevated muscle enzymes. MRI findings consistent with myositis were present in 70% (n = 19/27) of the subjects, and muscle biopsy confirmed JDM in 9 cases (30%). Among 25 patients tested for myositis specific antibodies, NXP2 (n = 3), Anti-TIF1 (n = 2), Anti-Mi-2 (n = 1), and MDA5 (n = 1) were detected, showing expected correlations with disease phenotype. Corticosteroids were universally administered, with methotrexate (n = 25; 83%) and IVIG (n = 15; 50%) as common adjuncts. Calcinosis was observed in 8 patients (27%), and was managed with various treatment modalities including pamidronate (n = 3), diltiazem (n = 2), and infliximab (n = 1). At the last follow-up, 18 patients (60%) were in clinical remission, 50% (n = 15) followed a polyphasic or chronic disease course, and 2 patients succumbed to disease-related complications.

Conclusions: This study provides comprehensive characterization of pediatric JDM in Oman. The findings highlight regional variations in disease presentation, autoantibody profiles, and treatment responses, underscoring the need for early diagnosis and individualized management strategies. Continued follow-up is essential to optimize long-term outcomes and improve survival rates in this patient population.

Background: The use of immune checkpoint inhibitor (ICI) therapy is increasing in pediatric oncology. ICIs can cause rheumatic-immune related adverse events (Rh-irAEs) such as inflammatory arthritis and myositis. Few case reports detail Rh-irAEs and their management in the pediatric population. Our objective was to assess the familiarity of pediatric rheumatologists (PRs) worldwide with Rh-irAEs, gauge confidence in managing these conditions, and identify knowledge gaps to guide future educational efforts.

Methods: We circulated an online survey to 2084 PRs via the "Dr. Peter Dent Pediatric Rheumatology Bulletin Board." Responses were collected from June 2024 to September 2024. We collected data on practitioner demographics, knowledge of ICIs and Rh-irAEs, confidence in managing Rh-irAEs, and preferred educational resources.

Results: Sixty-nine participants responded, of which 55 (80%) were PRs from academic centers. Despite global distribution, 56 (81%) responses came from North America. Thirty-four (49%) respondents were not aware of ICIs and their related mechanisms, indications, and side effects, and 40 (58%) were not familiar with irAEs. Fifty-five (80%) had never managed a patient with Rh-irAEs. Among those who had (14/69, 21%), the median number of cases managed was 2.0 (IQR 0.0). Thirty-nine respondents were "not confident at all" managing Rh-irAEs, 34 were "not confident at all" managing pre-existing autoimmune diseases (PAD) in ICI users, and 46 were "not confident at all" advising oncology colleagues on initiating or discontinuing ICIs in the context of Rh-irAEs or pre-existing autoimmune diseases (PAD). No respondents felt "completely confident" managing these conditions. Participants identified knowledge gaps in long-term management, acute management, and recognition and diagnosis. Forty-three indicated the need for pediatric-specific clinical guidelines. Of the 14 respondents with clinical experience treating Rh-irAEs, treatment varied, with 4 using nonsteroidal anti-inflammatory drugs, 3 using prednisone, and 4 combining prednisone with methotrexate. Long-term management also varied, with 5 using methotrexate, and 3 using tumor necrosis factor inhibitors.

Conclusions: Significant knowledge gaps and a lack of confidence exist among PRs managing ICI-related Rh-irAEs. As ICI use increases in pediatric oncology, PRs' exposure to Rh-irAEs will follow. Targeted educational programs and clinical guidelines may be valuable to address these gaps.

Background: Musculoskeletal (MSK) symptoms are a frequent presentation in pediatric patients and may arise from a range of conditions, including juvenile idiopathic arthritis (JIA) and malignancies. Differentiating cancer-related MSK symptoms from JIA at initial presentation remains challenging due to overlapping clinical features. Delays in the diagnosis of malignancy can result in significant morbidity, underscoring the need for reliable diagnostic tools. The ONCOREUM score was developed to distinguish malignancies presenting with arthropathy from JIA and demonstrated high performance in initial validation. However, its utility is limited to patients with arthropathy and does not extend to other forms of MSK involvement. This study aimed to validate the ONCOREUM score in patients with arthropathy and to develop an expanded predictive model to distinguish cancer-related MSK symptoms from JIA.

Methods: Patients aged < 16 years diagnosed with cancer or JIA were included. This retrospective study was conducted in two phases: (1) Evaluating the ability of the ONCOREUM score to identify cancer with arthropathy, (2) Developing a model to differentiate cancer-related MSK symptoms from JIA using stepwise logistic regression analysis.

Results: A total of 1,026 patients were reviewed (646 cancer, 380 JIA). In phase 1, 26 cancer patients (4.0%) and 351 JIA patients (92.4%) were included. The ONCOREUM score (cutoff = - 6) had a sensitivity of 88.5% and specificity of 65.0%, with an AUC of 0.77. In phase 2, MSK symptoms were present in 84 (13%) cancer cases (61 hematologic, 23 solid tumors). The best-fitting model was obtained through multivariable analysis: back pain (OR 15.58, 95% CI 2.77-87.64, p < 0.02), nocturnal pain (OR 789.97, 95% CI 51.26-12,175.54, p < 0.0001), limb bone pain (OR 24.11, 95% CI 6.91-84.12, p < 0.0001), pallor (OR 6.30, 95% CI 1.55-25.60, p < 0.01), morning stiffness (OR 0.03, 95% CI 0.002-0.57, p < 0.02), additive arthritis (OR 0.003, 95% CI 0.00-0.04, p < 0.0001), and monoarticular involvement (OR 0.02, 95% CI 0.00-0.23, p < 0.002). This model yielded an AUC of 0.99 (95% CI 0.98-0.99).

Conclusions: The refined predictive model is a promising clinical tool for differentiating cancer-associated MSK symptoms from JIA.