Pediatric Rheumatology最新文献

Background: NSAIDs are commonly used as first line therapy in chronic nonbacterial osteomyelitis (CNO) but are not effective for all patients. The objective of this study was to identify clinical variables associated with NSAID monotherapy response versus requiring second-line medication in a single-center cohort of patients with CNO.

Methods: The charts of children with CNO who attended a CNO clinic at a quaternary care center between 1/1/05 and 7/31/21 were retrospectively reviewed. Patients were divided into 3 groups: NSAID-short (NSAID monotherapy for 3 to < 7 months), NSAID-long (NSAID monotherapy for ≥ 7 months), or second-line treatment. Patients were also categorized by which bodily regions were affected by CNO. Multiple linear and logistic regression models were constructed to predict total NSAID monotherapy days and the odds of needing second-line treatment, respectively. These models were optimized using variable combinations that minimized multicollinearity and maximized predictive power, as indicated by minimized AIC values.

Results: One-hundred-sixty-four patients fulfilled inclusion criteria. Thirty-two patients were in the NSAID-short group, 62 in the NSAID-long group, and 70 in the second-line treatment group. Comparing the two NSAID groups showed that patients with unifocal disease at diagnosis required 47% fewer days of NSAIDs than those with multifocal disease. Results from logistic regression indicated that for each additional region affected, the odds of needing second line treatment increased by 1.94 times (p = 0.01) and that patients with symmetric bone lesions were 6.86 times more likely to require second-line treatment (p < 0.001).

Conclusions: Patients with unifocal CNO involvement at diagnosis were more likely to require shorter NSAID treatment. Patients with more regions affected and those with symmetric bone lesions were more likely to require second-line treatment.

Background: Pediatric patients with Eosinophilic Granulomatosis with Polyangiitis (EGPA) are at an increased risk of arterial and venous thromboembolism (AVTE). Although the exact mechanisms underlying AVTE remain unclear, eosinophils play a pivotal role in AVTE.

Main body: Current guidelines lack evidence-based recommendations, particularly concerning anticoagulant and antiplatelet treatments for this condition. Herein, we document a pediatric EGPA patient with deep venous thrombosis presenting with massive pulmonary thromboembolism during a relapse, treated with immunosuppressive and anticoagulant therapy to raise awareness among clinicians. Additionally, we performed a literature review to highlight various aspects of pediatric AVTE. Moreover, we evaluated the management strategies employed for the patients identified in the literature review and summarized the current practice guidelines regarding pediatric EGPA patients with AVTE to provide recommendations to clinicians on the management of this challenging complication.

Conclusions: Most AVTE events occur during periods of high disease activity. Notably, EGPA patients with VTE often present with thrombocytopenia due to consumption, a finding not typically expected during disease exacerbation. Venous thrombosis generally requires both anticoagulation and immunosuppressive treatment. Although our review indicates a favorable prognosis for AVTE, the small number of reported cases prevents us from drawing definitive conclusions. Future studies should explore the efficacy of mepolizumab and other eosinophil-targeted therapies for AVTE, in addition to investigating the roles of anticoagulation and antiplatelet treatments.

Objective: This systematic search and review aimed to evaluate the available literature on discontinuation of adalimumab and other tumor necrosis factor inhibitors (TNFi) for patients with well-controlled chronic inflammatory arthritides.

Methods: We conducted a publication search on adalimumab discontinuation from 2000-2023 using PubMed, CINAHL, EMBASE, and Cochrane Library. Included studies evaluated adalimumab discontinuation approaches, tapering schemes, and outcomes including successful discontinuation and recapture after flare, in patients with well-controlled disease. Studies included evaluated rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and juvenile idiopathic arthritis (JIA).

Results: Forty-nine studies were included. Studies evaluating adalimumab alone were limited, and many reported TNFi outcomes as a single entity. Studies on rheumatoid arthritis (RA) (32, 8 RCTs) reported flare rates from 33-87%. Flares with medication tapering were slightly lower than with abrupt stop, and successful recapture was generally high (80-100%). Studies on spondyloarthropathy (12, 4 RCTs), focused on tapering, noting lower flare rates in tapering rather than abruptly stopping, and high recapture rates (~ 90%). Studies on JIA (5) were observational and demonstrated modestly lower flare rates with tapering (17-63%) versus abrupt stopping (28-82%). There was notable variability in study design, follow-up duration, specificity for TNFi results, and controlled pediatric studies.

Conclusion: The literature evaluating adalimumab and other TNFi discontinuation, flare rates, and recapture success within the inflammatory arthritis population demonstrated less flare when medications were tapered, over abrupt stop in the RA, spondyloarthropathy, and JIA populations. When medications were restarted after flare, recapture of well-controlled disease was generally high in RA and spondyloarthropathy, and generally favorable in JIA.

Background: Juvenile idiopathic arthritis (JIA) is challenging to classify and effectively monitor due to the lack of disease- and subtype-specific biomarkers. A robust molecular signature that tracks with specific JIA features over time is urgently required, and targeted plasma metabolomics may reveal such a signature. The primary aim of this study was to characterise the differences in the plasma metabolome between JIA patients and non-JIA controls and identify specific markers of JIA subtype. We also assessed the extent to which these signatures are due to underlying inflammation as assessed by glycoprotein acetyls (GlycA) and high-sensitivity C-Reactive Protein (hsCRP) levels.

Methods: Targeted nuclear magnetic resonance (NMR) metabolomic profiles of plasma of 72 children with JIA and 18 controls were assessed cross-sectionally. Associations between 71 metabolomic biomarkers and JIA, JIA subtype, disease activity status, and inflammation markers (GlycA and hsCRP) were assessed using multivariable linear regression models.

Results: JIA was associated with higher GlycA (mean difference = 0.93 standard deviations, 95% confidence interval = [0.370, 1.494], P_adj = 0.039) and docosahexaenoic acid (1.06, [0.51, 1.60], P_adj = 0.021), and lower acetate (-0.92, [-1.43, -0.41], P_adj = 0.024) relative to controls. This variation was largely driven by systemic JIA (sJIA), with 24 of 71 total biomarkers significantly different (P_adj <0.05) relative to controls. There were no specific differences identified in oligoarticular (oJIA) or polyarticular (rheumatoid factor positive or negative) JIA relative to controls. Despite being generally highly correlated with hsCRP (r > 0.70), GlycA, but not hsCRP, was positively associated with active disease in sJIA (0.22, [-0.40, -0.04], P_adj = 0.018), and 6 of 24 sJIA-associated markers were associated with GlycA levels. Only 1 sJIA-associated biomarker, histidine, was associated with hsCRP levels.

Conclusion: Differences in the plasma NMR metabolomic profiles are apparent in children with sJIA, but not other JIA subtypes, relative to non-JIA controls. These findings suggest a potential utility for classifying and monitoring JIA through metabolomic profiling, with chronic inflammation, measured by GlycA, potentially playing a role in at least some of these metabolomic differences.

Background: Aicardi-Goutières Syndrome is a monogenic type 1 interferonopathy with infantile onset, characterized by a variable degree of neurological damage. Approximately 7% of Aicardi-Goutières Syndrome cases are caused by pathogenic variants in the ADAR gene and are classified as Aicardi-Goutières Syndrome type 6. Here, we present a new homozygous pathogenic variant in the ADAR gene. Currently, Janus Kinase inhibitors have been proposed to treat selected interferonopathies such as Aicardi-Goutières Syndrome, although limited information is available on its use and results in the neonatal presentation of this disease.

Case presentation: We present two siblings, a male neonate with congenital petechial rash, severe thrombopenia and generalized hypotonia and his deceased sister who had normal development until 5 months of age, when she suffered acute encephalopathy. We describe the clinical course, complementary examinations and follow-up with early treatment of the newborn with ruxolitinib. The homozygous variant c.2908G > A (p.Ala970Thr) in the ADAR gene was found in both siblings, parents were heterozygous carriers.

Conclusions: The homozygous variant c.2908G > A (p.Ala970Thr) in the ADAR gene causes Aicardi-Goutières Syndrome type 6. Intrafamilial phenotypic spectrum of the disease varies among individuals with the same pathogenic variant. Early initiation of ruxolitinib improved systemic signs but did not prevent the progression of neurological disease.

Background: Primary small vessel CNS vasculitis (sv-cPACNS) is a challenging inflammatory brain disease in children. Brain biopsy is mandatory to confirm the diagnosis. This study aims to develop and validate a histological scoring tool for diagnosing small vessel CNS vasculitis.

Methods: A standardized brain biopsy scoring instrument was developed and applied to consecutive full-thickness brain biopsies of pediatric cases and controls at a single center. Stains included immunohistochemistry and Hematoxylin & Eosin. Nine North American neuropathologists, blinded to patients' presentation, diagnosis, and therapy, scored de-identified biopsies independently.

Results: A total of 31 brain biopsy specimens from children with sv-cPACNS, 11 with epilepsy, and 11 with non-vasculitic inflammatory brain disease controls were included. Angiocentric inflammation in the cortex or white matter increases the likelihood of sv-cPACNS, with odds ratios (ORs) of 3.231 (95CI: 0.914-11.420, p = 0.067) and 3.923 (95CI: 1.13-13.6, p = 0.031). Moderate to severe inflammation in these regions is associated with a higher probability of sv-cPACNS, with ORs of 5.56 (95CI: 1.02-29.47, p = 0.046) in the cortex and 6.76 (95CI: 1.26-36.11, p = 0.025) in white matter. CD3, CD4, CD8, and CD20 cells predominated the inflammatory infiltrate. Reactive endothelium was strongly associated with sv-cPACNS, with an OR of 8.93 (p = 0.001). Features reported in adult sv-PACNS, including granulomas, necrosis, or fibrin deposits, were absent in all biopsies. The presence of leptomeningeal inflammation in isolation was non-diagnostic.

Conclusion: Distinct histological features were identified in sv-cPACNS biopsies, including moderate to severe angiocentric inflammatory infiltrates in the cortex or white matter, consisting of CD3, CD4, CD8, and CD20 cells, alongside reactive endothelium with specificity of 95%. In the first study of its kind proposing histological criteria for evaluating brain biopsies, we aim to precisely characterize the type and severity of the inflammatory response in patients with sv-cPACNS; this can enable consolidation of this population to assess outcomes and treatment methodologies comprehensively.

Background: Juvenile Idiopathic Arthritis (JIA) is a chronic pediatric illness, whereby youth experience physical, emotional and psychosocial challenges that result in reduced health related quality of life (HRQL). Peer mentoring has been shown to improve disease self-management in adults with chronic conditions, with mixed results in younger populations. Building on our pilot work - which supported the feasibility and initial effectiveness of the iPeer2Peer program - the objective of this study was to assess the clinical effectiveness of the program in youth with JIA through a waitlist randomized controlled trial.

Methods: Eighty-one youth (aged 12-18) were randomized to the intervention group and matched with trained peer mentors (18-25 years; successfully managing their JIA), completing of up to ten 30-min video calls over a 15-week period. Eighty-three youth in the control group received standard care. Outcome assessments occurred at enrollment, 15 weeks post randomization and 6-months post randomization. The primary outcome was self-management, measured using the TRANSITION-Q. Secondary outcomes were HRQL, pain, emotional distress, disease knowledge, self-efficacy, and perceived social support. These were assessed using linear mixed effects models. Content analysis of semi-structured interviews and focus groups was used to assess satisfaction with the program with mentors and mentees upon study completion.

Results: In total, 164 youth (mean age 14.4 ± 1.9 years, 78% female) were randomized to the study. The proposed sample size was not reached due to challenges in recruitment, likely impacted by the COVID-19 pandemic. The iPeer2Peer program did not show significant improvement in self-management (p = 0.7), or any of the secondary outcomes. Three key categories emerged from content analysis: (1) Fulfillment and Support Through Shared Experience, (2) Enhancing Program Delivery and (3) Strategies to Boost Engagement. These findings highlight that mentees valued the ability to converse with mentors who empathized with their disease experience, while mentors found it fulfilling to support mentees, and noted that they could have benefited from this type of support themselves.

Conclusion: While the iPeer2Peer did not result insignificant changes in clinical outcomes, both mentors and mentees were satisfied with the program and felt that mentorship provided real-world benefits for disease management and overall wellbeing.

Trial registration: ClinicalTrials.gov, NCT03116763. Registered 31, March 2017, https://www.

Clinicaltrials: gov/study/NCT03116763.

Background: This study aims to develop Z-Score models to normalize measurements of three coronary arteries and enhance the diagnosis of Kawasaki disease (KD) in children from newborns to 10 years old. Developing a reliable Z-Score model is challenging, as some existing models fail the normality test. Overcoming these challenges is crucial for improving KD diagnosis.

Method: Detailed measurements of the left main coronary artery (LCA), left anterior descending coronary artery (LAD), and right coronary artery (RCA) were collected, along with patient demographics such as age, height, weight, and body surface area (BSA). Several Z-Score models, named the Kuo Z-Score models, were proposed, with separate designs for different coronary arteries and different age groups, resulting in multiple Z-Score models. The Z-Score model for the RCA employs the Box-Cox method for data transformation. Finally, we tested various age group combinations, selecting models that passed the Anderson-Darling normality test and had higher R-square values for robustness and best data fit.

Results: The study included 1180 participants free from coronary or heart diseases. The Kuo Z-Score models were optimized for LCA, LAD, and RCA across the five age groups 0-6 years, 6-7 years, 7-8 years, 8-9 years, and 9-10 years. Only the normality test for the RCA in the 7-8 year age group failed. The proposed model fitted to the normality assumption outperforming the other models.

Conclusion: The Kuo Z-Score models, applicable across a broad age range, provides robust identification of coronary artery dilatation and aneurysm in KD. The models' capability to normalize diverse data sets marks a significant advancement in KD diagnostic sensitivity, aiding in better clinical decision-making and potentially improving patient outcomes.

Background: Most patients with a pediatric rheumatic disease are at increased risk of influenza due to immunosuppressive medication use. Despite initial quality improvement efforts, our influenza vaccination rate plateaued at 72%, which prompted a survey of patients and families to assess provider vaccine recommendations, influenza knowledge, and barriers to influenza vaccination.

Methods: Patients on immunosuppressive medication or their parent were eligible to complete a survey between July 2019 and January 2020. Survey questions assessed demographics, rheumatology diagnosis, immunosuppressive medication(s), influenza vaccination recommendation, patient/parent influenza knowledge, and barriers to influenza vaccination. Influenza vaccination rates for immunosuppressed patients were acquired each influenza season from 2015-2020 and tracked on a control chart.

Results: Of the 226 completed surveys, 145 (64.2%) were completed by parents and 81 (35.8%) by patients. The majority (85%) reported the influenza vaccine was recommended. The most common reasons for not receiving the influenza vaccine included: worry about disease flare (25.6%), concern the vaccine will cause influenza (25.6%), and lack of vaccine effectiveness (20.5%). Parents (40.9%) were more worried about disease flare compared to patients (17%; p = 0.024). Most respondents were able to correctly answer fever, cough and/or congestion as the most common symptoms of influenza; however, 23% answered gastrointestinal symptoms and 10.2% joint swelling. Most respondents (95.1%) were aware that immunosuppressive medication increases risk of infection. The average weekly influenza vaccination rate for the 2019-2020 flu season was 85.5%, which increased from 72.0% the previous year. Parents with higher education status were more likely to have their child receive the influenza vaccine compared to parents with less education.

Conclusions: This survey indicates that respondents understand the potential severity of influenza and the increased risk of infection due to immunosuppressive medication use; however, many inaccurately identified the most common symptoms of influenza and also reported misconceptions of influenza vaccine risks. The barriers identified in this survey will help drive future improvement efforts to increase influenza vaccination rates in this high-risk population.