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Frontiers in Pediatrics 2024Rice body synovitis (RBS) is a rare disease, especially in children. Rheumatoid disorders and tuberculosis are the first two reasons for the formation of the RB. The...
Rice body synovitis (RBS) is a rare disease, especially in children. Rheumatoid disorders and tuberculosis are the first two reasons for the formation of the RB. The diagnosis is mainly based on imaging and histopathological features. Herein, we report three cases of RBS in children diagnosed with congenital synovial chondromatosis, tuberculosis (unconfirmed), and ANA -positive juvenile idiopathic arthritis. Clinical features, radiographic findings, pathophysiology, treatment process, and prognosis were reviewed and documented meticulously to enhance cognition in this population and provide some references for clinicians in diagnosing and treating the disease.
PubMed: 38938505
DOI: 10.3389/fped.2024.1391229 -
Arthritis & Rheumatology (Hoboken, N.J.) Jun 2024To evaluate whether there is an enrichment of rare variants in familial hemophagocytic lymphohistiocytosis (HLH)-associated genes among patients with systemic juvenile...
OBJECTIVE
To evaluate whether there is an enrichment of rare variants in familial hemophagocytic lymphohistiocytosis (HLH)-associated genes among patients with systemic juvenile idiopathic arthritis (sJIA) with or without macrophage activation syndrome (MAS).
METHODS
Targeted sequencing of HLH genes (LYST, PRF1, RAB27A, STX11, STXBP2, UNC13D) was performed in sJIA subjects from an established cohort. Sequence data from control subjects were obtained in silico (dbGaP:phs000280.v8.p2). Rare variant association testing (RVT) was performed with sequence kernel association test (SKAT) package. Significance was defined as p < 0.05 after 100,000 permutations.
RESULTS
Sequencing data from 524 sJIA cases were jointly called and harmonized with exome-derived target data from 3000 controls. Quality control operations produced a set of 480 cases and 2924 ancestrally-matched control subjects. RVT of cases and controls revealed a significant association with rare protein-altering variants (minor allele frequency [MAF] < 0.01) of STXBP2 (p = 0.020), and ultra-rare variants (MAF < 0.001) of STXBP2 (p = 0.006) and UNC13D (p = 0.046). A sub-analysis of 32 cases with known MAS and 90 without revealed a significant difference in the distribution of rare UNC13D variants (p = 0.0047) between the groups. Additionally, sJIA patients more often carried ≥ 2 HLH variants than did controls (p = 0.007), driven largely by digenic combinations involving LYST.
CONCLUSION
We identified an enrichment of rare HLH variants in sJIA patients compared with controls, driven by STXBP2 and UNC13D. Biallelic variation in HLH genes was associated with sJIA, driven by LYST. Only UNC13D displayed enrichment in patients with MAS. This suggests that HLH variants may contribute to the pathophysiology of sJIA, even without MAS.
PubMed: 38937141
DOI: 10.1002/art.42938 -
Arthritis Care & Research Jun 2024The objective was to develop consensus treatment plans (CTPs) for patients with refractory moderately severe juvenile dermatomyositis (JDM) treated with biologic...
OBJECTIVE
The objective was to develop consensus treatment plans (CTPs) for patients with refractory moderately severe juvenile dermatomyositis (JDM) treated with biologic disease-modifying antirheumatic drugs (bDMARDs).
METHODS
The Biologics Workgroup of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) JDM Research Committee used case-based surveys, consensus framework, and nominal group technique to produce bDMARD CTPs for patients with refractory moderately severe JDM.
RESULTS
Four bDMARD CTPs were proposed: TNF-alpha inhibitor (adalimumab or infliximab), abatacept, rituximab, and tocilizumab. Each CTP has different options for dosing and/or route. Among 76 respondents, consensus was achieved for the proposed CTPs (93% [67/72]) as well as for patient characteristics, assessments, outcome measures, and follow up. By weighted average, respondents indicated that they would most likely use rituximab followed by abatacept, TNF-alpha inhibitor, and tocilizumab.
CONCLUSION
CTPs for the use of bDMARDs in refractory moderately severe JDM were developed using consensus methodology. The implementation of the bDMARD CTPs will lay the groundwork for registry-based prospective comparative effectiveness studies.
PubMed: 38937134
DOI: 10.1002/acr.25393 -
Archives of Rheumatology Jun 2024This study aimed to investigate coronavirus disease 2019 (COVID-19) vaccination rates and factors affecting vaccination in children with rheumatic diseases.
OBJECTIVES
This study aimed to investigate coronavirus disease 2019 (COVID-19) vaccination rates and factors affecting vaccination in children with rheumatic diseases.
PATIENTS AND METHODS
This multicenter cross-sectional survey-based study was conducted between July 2022 and September 2022. Four hundred seventy-four patients (256 females, 218 males; median age: 15 years; interquartile range, 13 to 16 years) were included in the patient group, and 211 healthy children (124 females, 87 males; median age: 15 years; interquartile range, 13 to 16 years) were included in the control group. A questionnaire was administered to the parents face-to-face during routine outpatient visits.
RESULTS
Of the patients, 220 were followed up with the diagnosis of autoinflammatory disease, 174 with juvenile idiopathic arthritis, 48 with connective tissue disease, 23 with vasculitis, eight with uveitis, and one with sarcoidosis. In the study group, 256 (54%) patients and 115 (54.5%) healthy children received at least one dose of COVID-19 vaccine. Parents' concern regarding potential side effects of the vaccine was the most common reason for COVID-19 vaccination hesitancy in both groups. The median patient age, follow-up period, colchicine treatment rates, childhood vaccination and influenza vaccination rates, median parental age, parental vaccination rate, and parental education level were higher in vaccinated patients (p<0.001).
CONCLUSION
Parents' concerns about safety and side effects were found to be the most important factors affecting vaccination success. Identification of the underlying causes of parental vaccine hesitancy will facilitate the development of effective vaccination strategies for potential future outbreaks.
PubMed: 38933728
DOI: 10.46497/ArchRheumatol.2024.10356 -
Archives of Rheumatology Jun 2024This study aimed to assess the readiness of our patient population for the transfer to adult care and the applicability of the TRANSITION-Q and STARx scales to the...
OBJECTIVES
This study aimed to assess the readiness of our patient population for the transfer to adult care and the applicability of the TRANSITION-Q and STARx scales to the Turkish adolescent patient population.
PATIENTS AND METHODS
A total of 153 patients (92 males, 61 females; mean age: 15.5±1.9 years; range, 12 to 18 years) were included in the study between September 15, 2021, and December 15, 2021. The patients were divided into two groups according to age groups: 12 to 15 years old and 16 to 18 years old. The patients were also divided into four groups according to their diagnosis: connective tissue diseases, juvenile idiopathic arthritis, vasculitis, and autoinflammatory diseases. The TRANSITION-Q and STARx scales were administered face-to-face by a nurse and a doctor. The transition readiness of the patients was evaluated according to their scores.
RESULTS
Sixty-nine (45%) patients were in the 12 to 15 age group, and 84 (55%) were in the 16 to 18 age group. Eight-four (54.9%) patients had juvenile idiopathic arthritis, 47 (30.7%) patients had an autoinflammatory disease, 14 (9.2%) patients had vasculitis, and eight (5.2%) patients had a connective tissue disease. There was no significant difference in the scale scores according to disease groups and sexes in both scales. Considering the age of the patients, the mean scores of the patients in the 16 to 18 age group were found to be significantly higher compared to the 12 to 15 age group for both the TRANSITION-Q (74.3±13.3 65.4±9.6, p<0.001) and STARx scales (51.8±8.1 44.8±9.1, p<0.001). Cronbach's alpha score was 0.71 for the STARx scale and 0.79 for the TRANSITION-Q scale.
CONCLUSION
TRANSITION-Q and STARx scales could guide the Turkish patient population in determining the pretransition needs of patients in planning individualized transition processes.
PubMed: 38933719
DOI: 10.46497/ArchRheumatol.2024.10379 -
Life (Basel, Switzerland) May 2024(1) Background: Achieving inactive disease decreases long-term joint damage in patients with polyarticular juvenile idiopathic arthritis (polyJIA). The aim of our study...
(1) Background: Achieving inactive disease decreases long-term joint damage in patients with polyarticular juvenile idiopathic arthritis (polyJIA). The aim of our study was to describe average time to treatment and medication changes over time. (2) Methods: Incident polyJIA patients were retrospectively identified in the InGef and WIG2 longitudinal health claims databases. Drug escalation level changes were evaluated longitudinally and cross-sectionally across three years, as follows: no treatment, glucocorticoids (GCs) and/or non-steroidal anti-inflammatory drugs (NSAIDs), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and biological disease-modifying antirheumatic drugs (bDMARDs). (3) Results: On average, newly diagnosed polyJIA patients received their first csDMARD prescription after 128 days and their first bDMARD prescription after 327 days. More patients were treated with csDMARDs than with bDMARDs at diagnosis; however, 24% and 12% (InGef and WIG2 databases, respectively) had no JIA treatment. After three years, 45% and 31% were not taking any treatments, while 18% and 36% were prescribed bDMARDs. Among patients initiating bDMARDs, most continued treatment for three years, with some switching to csDMARDs or discontinuing treatment. Patients treated only with csDMARDs took them longer, compared to those additionally taking other DMARDs. Patients treated with bDMARDs took them about twice as long as the csDMARDs they took prior. (4) Conclusion: A substantial number of patients with polyJIA are not treated as intensively as guidelines recommend.
PubMed: 38929695
DOI: 10.3390/life14060712 -
Children (Basel, Switzerland) Jun 2024an accurate assessment of the immunity against SARS-CoV-2 can facilitate a better understanding and management of not only the recent coronavirus but similar pathogens...
Application of Interferon-γ Release Assay in the Assessment of T-Cell Immunity to SARS-CoV-2 Antigens in the Cohort of Pediatric Patients with Juvenile Idiopathic Arthritis.
an accurate assessment of the immunity against SARS-CoV-2 can facilitate a better understanding and management of not only the recent coronavirus but similar pathogens as well. the aim of this study was to evaluate T-cell immunity with reference to antibody titers in a group of pediatric patients with autoimmune arthritides utilizing the widely known Interferon-γ Release Assay (IGRA). This study was conducted in the cohort of 55 children suffering from Juvenile Idiopathic Arthritis (JIA). This research analyzed the SARS-CoV-2 T-cell response measured by a specific quantitative IGRA, followed by a serological ELISA test measuring the presence and quantity of IgG, IgM, and IgA antibodies in serum. The cellular response to SARS-CoV-2 measured by the IGRA test significantly correlated with the antibody titers, IgA ( < 0.00003, R = 0.537), IgG ( < 0.0001, R = 0.668), and IgG nucleocapsid protein (NCP) ( < 0.003, R = 0.0399), with no correlation with IgM levels. The antibody levels in patients receiving biological agents were significantly lower compared to the rest of the cohort ( = 0.0369), while traditional disease-modifying antirheumatic drugs had no such effect. the main limitation of the research is the small sample size, mostly due to the specific cohort of patients and the lack of a healthy control. IGRA appears to be a viable tool in the accurate evaluation of T-cell responses to SARS-CoV-2, and serodiagnostics alone is not always sufficient in the assessment of immune responses.
PubMed: 38929315
DOI: 10.3390/children11060736 -
Biomedicines Jun 2024T cell activation is critical for an effective immune response against pathogens. However, dysregulation contributes to the pathogenesis of autoimmune diseases,...
T cell activation is critical for an effective immune response against pathogens. However, dysregulation contributes to the pathogenesis of autoimmune diseases, including Juvenile Idiopathic Arthritis (JIA). The molecular mechanisms underlying T cell activation are still incompletely understood. T cell activation promotes the acetylation of histone 3 at Lysine 27 (H3K27ac) at enhancer and promoter regions of proinflammatory cytokines, thereby increasing the expression of these genes which is essential for T cell function. Co-activators E1A binding protein P300 (P300) and CREB binding protein (CBP), collectively known as P300/CBP, are essential to facilitate H3K27 acetylation. Presently, the role of P300/CBP in human CD4+ T cells activation remains incompletely understood. To assess the function of P300/CBP in T cell activation and autoimmune disease, we utilized iCBP112, a selective inhibitor of P300/CBP, in T cells obtained from healthy controls and JIA patients. Treatment with iCBP112 suppressed T cell activation and cytokine signaling pathways, leading to reduced expression of many proinflammatory cytokines, including IL-2, IFN-γ, IL-4, and IL-17A. Moreover, P300/CBP inhibition in T cells derived from the inflamed synovium of JIA patients resulted in decreased expression of similar pathways and preferentially suppressed the expression of disease-associated genes. This study underscores the regulatory role of P300/CBP in regulating gene expression during T cell activation while offering potential insights into the pathogenesis of autoimmune diseases. Our findings indicate that P300/CBP inhibition could potentially be leveraged for the treatment of autoimmune diseases such as JIA in the future.
PubMed: 38927552
DOI: 10.3390/biomedicines12061344 -
International Journal of Rheumatic... Jun 2024Mixed connective tissue disease (MCTD) is a rare entity in children. There is a paucity of studies on juvenile-onset MCTD (jMCTD) worldwide especially from Southeast...
INTRODUCTION
Mixed connective tissue disease (MCTD) is a rare entity in children. There is a paucity of studies on juvenile-onset MCTD (jMCTD) worldwide especially from Southeast Asia.
OBJECTIVES
To describe clinical and laboratory features of jMCTD diagnosed at pediatric rheumatology centers across India.
METHODS
A predesigned detailed case proforma in an excel format was prepared and was sent to all the Pediatric Rheumatology centers in India. Eleven centers provided the clinical and laboratory data of their jMCTD patients, which was then compiled and analyzed in detail.
RESULTS
Thirty-one jMCTD patients from 11 centers were included in the study. Our cohort had 27 females and four male patients over 12 months (August 2021 to July 2022). The median age at presentation was 12 years (range 5-18 years) and the median duration of symptoms was 24 months at diagnosis (range 2-96 months). The common features included arthritis (90%), malar rash (70.9%), and Raynaud's phenomenon (70.9%). At a mean follow-up of 43 months (range 1-168 months), 45% of them were in remission. There were two deaths reported, due to macrophage activation syndrome and sepsis respectively.
CONCLUSION
We present the largest multicenter experience on jMCTD from the Indian subcontinent. The study's findings serve as a crucial stepping stone toward unraveling the complexities of jMCTD and improving patient care and management strategies.
Topics: Humans; Child; Male; Female; Mixed Connective Tissue Disease; India; Adolescent; Child, Preschool; Treatment Outcome; Age of Onset; Immunosuppressive Agents; Antirheumatic Agents; Retrospective Studies; Time Factors; Remission Induction
PubMed: 38925615
DOI: 10.1111/1756-185X.15243 -
Arthritis & Rheumatology (Hoboken, N.J.) Jun 2024To report safety and efficacy of CD19-targeting CAR T cells in a child with refractory juvenile dermatomyositis (JDM).
OBJECTIVES
To report safety and efficacy of CD19-targeting CAR T cells in a child with refractory juvenile dermatomyositis (JDM).
PATIENTS AND METHODS
We describe the case of a 12-year-old Caucasian boy with severe, chronically active JDM, refractory to multiple immunosuppressive treatment lines, including B-cell depletion with rituximab. The patient received a single infusion of fresh, autologous, second-generation anti-CD19 CAR T-cell product (lentiviral vector) manufactured on the Prodigy device (1x10 CAR T cells/kg), after lymphodepletion with cyclophosphamide (1000 mg/m over 2 days) and fludarabine (90 mg/m over 3 days). Immunosuppressive and glucocorticoid treatment were withdrawn before leukapheresis and CAR T-cell infusion.
RESULTS
Before anti-CD19 CAR T-cell therapy, the patient had persistent severe skin and muscular disease activity. CAR T cells expanded significantly (peak at day 7, 32.69 cells/μL). Complete B-cell depletion was documented on day 5 in blood and at week 2 in bone marrow. The patient presented fever as part of mild cytokine release syndrome (G1), transient anemia (G2) and neutropenia (G4). Neither infection nor neurotoxicity were observed. Laboratory tests, MRI imaging, Physician's Global Assessment of disease activity (PGA), Childhood Myositis Assessment Scale (CMAS) and Cutaneous Assessment Tool for myositis (CAT) were performed at baseline and follow-up to assess treatment response, showing remarkable progressive improvement that persists over time, even after B-cell recovery.
CONCLUSIONS
This JDM patient with severe chronic disease, refractory to multiple treatments, achieved sustained B-cell depletion and ongoing immunosuppressive drug-free clinical and radiological improvement eight months after a single infusion of anti-CD19 CAR T cells.
PubMed: 38924652
DOI: 10.1002/art.42933