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  • 1
    Online Resource
    Online Resource
    Serum S100A8/A9 and S100A12 Levels in Children With Polyarticular Forms of Juvenile Idiopathic Arthritis: Relationship to Maintenance of Clinically Inactive Disease During Anti–Tumor Necrosis Factor Therapy and Occurrence of Disease Flare After Discontinuation of Therapy
    Wiley ; 2019
    In:  Arthritis & Rheumatology Vol. 71, No. 3 ( 2019-03), p. 451-459
    Details
    In: Arthritis & Rheumatology, Wiley, Vol. 71, No. 3 ( 2019-03), p. 451-459
    Abstract: To determine the relationship between serum levels of S100A8/A9 and S100A12 and the maintenance of clinically inactive disease during anti–tumor necrosis factor (anti‐ TNF ) therapy and the occurrence of disease flare following withdrawal of anti‐ TNF therapy in patients with polyarticular forms of juvenile idiopathic arthritis (JIA). Methods In this prospective, multicenter study, 137 patients with polyarticular‐course JIA whose disease was clinically inactive while receiving anti‐ TNF therapy were enrolled. Patients were observed for an initial 6‐month phase during which anti‐ TNF treatment was continued. For those patients who maintained clinically inactive disease over the 6 months, anti‐ TNF was withdrawn and they were followed up for 8 months to assess for the occurrence of flare. Serum S100 levels were measured at baseline and at the time of anti‐ TNF withdrawal. Spearman's rank correlation test, Mann‐Whitney U test, Kruskal‐Wallis test, receiver operating characteristic ( ROC ) curve, and Kaplan‐Meier survival analyses were used to assess the relationship between serum S100 levels and maintenance of clinically inactive disease and occurrence of disease flare after anti‐ TNF withdrawal. Results Over the 6‐month initial phase with anti‐ TNF therapy, the disease state reverted from clinically inactive to clinically active in 24 (18%) of the 130 evaluable patients with polyarticular‐course JIA ; following anti‐ TNF withdrawal, 39 (37%) of the 106 evaluable patients experienced a flare. Serum levels of S100A8/A9 and S100A12 were elevated in up to 45% of patients. Results of the ROC analysis revealed that serum S100 levels did not predict maintenance of clinically inactive disease during anti‐ TNF therapy nor did they predict disease flare after treatment withdrawal. Elevated levels of S100A8/A9 were not predictive of the occurrence of a disease flare within 30 days, 60 days, 90 days, or 8 months following anti‐ TNF withdrawal, and elevated S100A12 levels had a modest predictive ability for determining the risk of flare within 30, 60, and 90 days after treatment withdrawal. Serum S100A12 levels at the time of anti‐ TNF withdrawal were inversely correlated with the time to disease flare (r = −0.36). Conclusion Serum S100 levels did not predict maintenance of clinically inactive disease or occurrence of disease flare in patients with polyarticular‐course JIA , and S100A12 levels were only moderately, and inversely, correlated with the time to disease flare.
    Type of Medium: Online Resource
    ISSN: 2326-5191 , 2326-5205
    URL: Issue
    URL: Article
    DOI: 10.1002/art.2019.71.issue-3
    DOI: 10.1002/art.40727
    RVK:
    XA 10000
    RVK:
    XA 30325
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2754614-7
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  • 2
    Online Resource
    Online Resource
    Preliminary evidence on abatacept safety and efficacy in refractory juvenile localized scleroderma
    Oxford University Press (OUP) ; 2021
    In:  Rheumatology Vol. 60, No. 8 ( 2021-08-02), p. 3817-3825
    Details
    In: Rheumatology, Oxford University Press (OUP), Vol. 60, No. 8 ( 2021-08-02), p. 3817-3825
    Abstract: To evaluate the safety and efficacy of abatacept treatment for refractory juvenile localized scleroderma (jLS) in a retrospective study. Methods A multicentre cohort study was performed to evaluate jLS subjects treated with abatacept with follow-up for 12 months to maximum of 24 months. Assessments at 6-month intervals included skin activity measures and physician global assessment of activity (PGA-A). Descriptive statistical analysis was performed. Results Eighteen subjects were studied with median age of 13.4 years, the majority had linear scleroderma subtype, and musculoskeletal involvement. All had previously failed MTX and/or mycophenolate mofetil treatment and glucocorticoids. Abatacept was added to the subject’s maintenance DMARD treatment; 13 also received glucocorticoids at start of abatacept. No serious adverse events occurred. Skin activity and PGA-A scores declined in nearly all by 6 months and continued to improve from 6 to 12 months. At 12 months, 15 (83%) subjects were considered responders, two (11%) treatment failures, and one dropped out for adverse event. Response was sustained for 11 (61%) subjects to 18 months and eight (44%) to 24 months. Overall, four (22%) subjects were treatment failures and three (16.7%) discontinued abatacept for adverse event. Active musculoskeletal problems improved in most affected subjects. Ten subjects were able to discontinue initial glucocorticoid and six concomitant DMARD treatment. Conclusion Abatacept was found to be safe and effective for jLS subjects refractory to standard of care treatment. Subjects experienced improvement in both skin and musculoskeletal activity. Prospective studies should be performed to more fully evaluate abatacept’s efficacy.
    Type of Medium: Online Resource
    ISSN: 1462-0324 , 1462-0332
    URL: Article
    DOI: 10.1093/rheumatology/keaa873
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1474143-X
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  • 3
    Online Resource
    Online Resource
    Risk, Timing, and Predictors of Disease Flare After Discontinuation of Anti–Tumor Necrosis Factor Therapy in Children With Polyarticular Forms of Juvenile Idiopathic Arthritis With Clinically Inactive Disease
    Wiley ; 2018
    In:  Arthritis & Rheumatology Vol. 70, No. 9 ( 2018-09), p. 1508-1518
    Details
    In: Arthritis & Rheumatology, Wiley, Vol. 70, No. 9 ( 2018-09), p. 1508-1518
    Abstract: To determine the frequency, time to flare, and predictors of disease flare upon withdrawal of anti–tumor necrosis factor (anti‐ TNF ) therapy in children with polyarticular forms of juvenile idiopathic arthritis ( JIA ) who demonstrated ≥6 months of continuous clinically inactive disease. Methods In 16 centers 137 patients with clinically inactive JIA who were receiving anti‐ TNF therapy (42% of whom were also receiving methotrexate [ MTX ]) were prospectively followed up. If the disease remained clinically inactive for the initial 6 months of the study, anti‐ TNF was stopped and patients were assessed for flare at 1, 2, 3, 4, 6, and 8 months. Life‐table analysis, t ‐tests, chi‐square test, and Cox regression analysis were used to identify independent variables that could significantly predict flare by 8 months or time to flare. Results Of 137 patients, 106 (77%) maintained clinically inactive disease while receiving anti‐ TNF therapy for the initial 6 months and were included in the phase of the study in which anti‐ TNF therapy was stopped. Stopping anti‐ TNF resulted in disease flare in 39 (37%) of 106 patients by 8 months. The mean/median ± SEM time to flare was 212/250 ± 9.77 days. Patients with shorter disease duration at enrollment, older age at onset and diagnosis, shorter disease duration prior to experiencing clinically inactive disease, and shorter time from onset of clinically inactive disease to enrollment were found to have significantly lower hazard ratios for likelihood of flare by 8 months ( P 〈 0.05). Conclusion Over one‐third of patients with polyarticular JIA with sustained clinically inactive disease will experience a flare by 8 months after discontinuation of anti‐ TNF therapy. Several predictors of lower likelihood of flare were identified.
    Type of Medium: Online Resource
    ISSN: 2326-5191 , 2326-5205
    URL: Issue
    URL: Article
    DOI: 10.1002/art.2018.70.issue-9
    DOI: 10.1002/art.40509
    RVK:
    XA 10000
    RVK:
    XA 30325
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2754614-7
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  • 4
    Online Resource
    Online Resource
    Serologic and Cytokine Signatures in Children With Multisystem Inflammatory Syndrome and Coronavirus Disease 2019
    Oxford University Press (OUP) ; 2022
    In:  Open Forum Infectious Diseases Vol. 9, No. 3 ( 2022-03-01)
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 9, No. 3 ( 2022-03-01)
    Abstract: The serologic and cytokine responses of children hospitalized with multisystem inflammatory syndrome (MIS-C) vs coronavirus disease 2019 (COVID-19) are poorly understood. Methods We performed a prospective, multicenter, cross-sectional study of hospitalized children who met the Centers for Disease Control and Prevention case definition for MIS-C (n = 118), acute COVID-19 (n = 88), or contemporaneous healthy controls (n = 24). We measured severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) immunoglobulin G (IgG) titers and cytokine concentrations in patients and performed multivariable analysis to determine cytokine signatures associated with MIS-C. We also measured nucleocapsid IgG and convalescent RBD IgG in subsets of patients. Results Children with MIS-C had significantly higher SARS-CoV-2 RBD IgG than children with acute COVID-19 (median, 2783 vs 146; P  & lt; .001), and titers correlated with nucleocapsid IgG. For patients with MIS-C, RBD IgG titers declined in convalescence (median, 2783 vs 1135; P = .010) in contrast to patients with COVID-19 (median, 146 vs 4795; P  & lt; .001). MIS-C was characterized by transient acute proinflammatory hypercytokinemia, including elevated levels of interleukin (IL) 6, IL-10, IL-17A, and interferon gamma (IFN-γ). Elevation of at least 3 of these cytokines was associated with significantly increased prevalence of prolonged hospitalization ≥8 days (prevalence ratio, 3.29 [95% CI, 1.17–9.23]). Conclusions MIS-C was associated with high titers of SARS-CoV-2 RBD IgG antibodies and acute hypercytokinemia with IL-6, IL-10, IL-17A, and IFN-γ.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofac070
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2757767-3
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  • 5
    Online Resource
    Online Resource
    Distinguishing Multisystem Inflammatory Syndrome in Children From COVID-19, Kawasaki Disease and Toxic Shock Syndrome
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Pediatric Infectious Disease Journal Vol. 41, No. 4 ( 2022-04), p. 315-323
    Details
    In: Pediatric Infectious Disease Journal, Ovid Technologies (Wolters Kluwer Health), Vol. 41, No. 4 ( 2022-04), p. 315-323
    Abstract: Distinguishing multisystem inflammatory syndrome in children (MIS-C) from coronavirus disease 2019 (COVID-19), Kawasaki disease (KD), and toxic shock syndrome (TSS) can be challenging. Because clinical management of these conditions can vary, timely and accurate diagnosis is essential. Methods: Data were collected from patients 〈 21 years of age hospitalized with MIS-C, COVID-19, KD, and TSS in 4 major health care institutions. Patient demographics and clinical and laboratory data were compared among the 4 conditions, and a diagnostic scoring tool was developed to assist in clinical diagnosis. Results: A total of 233 patients with MIS-C, 102 with COVID-19, 101 with KD, and 76 with TSS were included in the analysis. Patients with MIS-C had the highest prevalence of decreased cardiac function (38.6%), myocarditis (34.3%), pericardial effusion (38.2%), mitral regurgitation (31.8%) and pleural effusion (34.8%) compared with patients with the other conditions. Patients with MIS-C had increased peak levels of C-reactive protein and decreased platelets and lymphocyte nadir counts compared with patients with COVID-19 and KD and elevated levels of troponin, brain natriuretic peptide and pro-brain natriuretic peptide compared with COVID-19. Diagnostic scores utilizing clinical findings effectively distinguished MIS-C from COVID-19, KD, and TSS, with internal validation showing area under the curve ranging from 0.87 to 0.97. Conclusions: Compared with COVID-19, KD, and TSS, patients with MIS-C had significantly higher prevalence of cardiac complications, elevated markers of inflammation and cardiac damage, thrombocytopenia, and lymphopenia. Diagnostic scores can be a useful tool for distinguishing MIS-C from COVID-19, KD, and TSS.
    Type of Medium: Online Resource
    ISSN: 0891-3668
    URL: Article
    DOI: 10.1097/INF.0000000000003449
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2020216-7
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  • 6
    Online Resource
    Online Resource
    Increased Sensitivity of the European Medicines Agency Algorithm for Classification of Childhood Granulomatosis with Polyangiitis
    The Journal of Rheumatology ; 2012
    In:  The Journal of Rheumatology Vol. 39, No. 8 ( 2012-08), p. 1687-1697
    Details
    In: The Journal of Rheumatology, The Journal of Rheumatology, Vol. 39, No. 8 ( 2012-08), p. 1687-1697
    Abstract: Granulomatosis with polyangiitis (Wegener’s; GPA) and other antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare in childhood and are sometimes difficult to discriminate. We compared use of adult-derived classification schemes for GPA against validated pediatric criteria in the ARChiVe (A Registry for Childhood Vasculitis e-entry) cohort, a Childhood Arthritis and Rheumatology Research Alliance initiative. Methods. Time-of-diagnosis data for children with physician (MD) diagnosis of AAV and unclassified vasculitis (UCV) from 33 US/Canadian centers were analyzed. The European Medicines Agency (EMA) classification algorithm and European League Against Rheumatism/Paediatric Rheumatology International Trials Organisation/Paediatric Rheumatology European Society (EULAR/PRINTO/PRES) and American College of Rheumatology (ACR) criteria for GPA were applied to all patients. Sensitivity and specificity were calculated (MD-diagnosis as reference). Results. MD-diagnoses for 155 children were 100 GPA, 25 microscopic polyangiitis (MPA), 6 ANCA-positive pauciimmune glomerulonephritis, 3 Churg-Strauss syndrome, and 21 UCV. Of these, 114 had GPA as defined by EMA, 98 by EULAR/PRINTO/PRES, and 87 by ACR. Fourteen patients were identified as GPA by EULAR/PRINTO/PRES but not by ACR; 3 were identified as GPA by ACR but not EULAR/PRINTO/PRES. Using the EMA algorithm, 135 (87%) children were classifiable. The sensitivity of the EMA algorithm, the EULAR/PRINTO/PRES, and ACR criteria for classifying GPA was 90%, 77%, and 69%, respectively, with specificities of 56%, 62%, and 67%. The relatively poor sensitivity of the 2 criteria related to their inability to discriminate patients with MPA. Conclusion. EULAR/PRINTO/PRES was more sensitive than ACR criteria in classifying pediatric GPA. Neither classification system has criteria for MPA; therefore usefulness in discriminating patients in ARChiVe was limited. Even when using the most sensitive EMA algorithm, many children remained unclassified.
    Type of Medium: Online Resource
    ISSN: 0315-162X , 1499-2752
    URL: Article
    DOI: 10.3899/jrheum.111352
    RVK:
    XA 10000
    Language: English
    Publisher: The Journal of Rheumatology
    Publication Date: 2012
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  • 7
    Online Resource
    Online Resource
    Assessing the Performance of the Birmingham Vasculitis Activity Score at Diagnosis for Children with Antineutrophil Cytoplasmic Antibody-associated Vasculitis in A Registry for Childhood Vasculitis (ARChiVe)
    The Journal of Rheumatology ; 2012
    In:  The Journal of Rheumatology Vol. 39, No. 5 ( 2012-05), p. 1088-1094
    Details
    In: The Journal of Rheumatology, The Journal of Rheumatology, Vol. 39, No. 5 ( 2012-05), p. 1088-1094
    Abstract: There are no validated tools for measuring disease activity in pediatric vasculitis. The Birmingham Vasculitis Activity Score (BVAS) is a valid disease activity tool in adult vasculitis. Version 3 (BVAS v.3) correlates well with physician’s global assessment (PGA), treatment decision, and C-reactive protein in adults. The utility of BVAS v.3 in pediatric vasculitis is not known. We assessed the association of BVAS v.3 scores with PGA, treatment decision, and erythrocyte sedimentation rate (ESR) at diagnosis in pediatric antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Methods. Children with AAV diagnosed between 2004 and 2010 at all ARChiVe centers were eligible. BVAS v.3 scores were calculated with a standardized online tool ( www.vasculitis.org ). Spearman’s rank correlation coefficient (r s ) was used to test the strength of association between BVAS v.3 and PGA, treatment decision, and ESR. Results. A total of 152 patients were included. The physician diagnosis of these patients was predominantly granulomatosis with polyangiitis (n = 99). The median BVAS v.3 score was 18.0 (range 0–40). The BVAS v.3 correlations were r s = 0.379 (95% CI 0.233 to 0.509) with PGA, r s = 0.521 (95% CI 0.393 to 0.629) with treatment decision, and r s = 0.403 (95% CI 0.253 to 0.533) with ESR. Conclusion. Applied to children with AAV, BVAS v.3 had a weak correlation with PGA and moderate correlation with both ESR and treatment decision. Prospective evaluation of BVAS v.3 and/or pediatric-specific modifications to BVAS v.3 may be required before it can be formalized as a disease activity assessment tool in pediatric AAV.
    Type of Medium: Online Resource
    ISSN: 0315-162X , 1499-2752
    URL: Article
    DOI: 10.3899/jrheum.111030
    RVK:
    XA 10000
    Language: English
    Publisher: The Journal of Rheumatology
    Publication Date: 2012
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  • 8
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    Online Resource
    Do Adult Disease Severity Subclassifications Predict Use of Cyclophosphamide in Children with ANCA-associated Vasculitis? An Analysis of ARChiVe Study Treatment Decisions
    The Journal of Rheumatology ; 2012
    In:  The Journal of Rheumatology Vol. 39, No. 10 ( 2012-10), p. 2012-2020
    Details
    In: The Journal of Rheumatology, The Journal of Rheumatology, Vol. 39, No. 10 ( 2012-10), p. 2012-2020
    Abstract: To determine whether adult disease severity subclassification systems for antineutrophil cytoplasmic antibody-associated vasculitis (AAV) are concordant with the decision to treat pediatric patients with cyclophosphamide (CYC). Methods. We applied the European Vasculitis Study (EUVAS) and Wegener’s Granulomatosis Etanercept Trial (WGET) disease severity subclassification systems to pediatric patients with AAV in A Registry for Childhood Vasculitis (ARChiVe). Modifications were made to the EUVAS and WGET systems to enable their application to this cohort of children. Treatment was categorized into 2 groups, “cyclophosphamide” and “no cyclophosphamide.” Pearson’s chi-square and Kendall’s rank correlation coefficient statistical analyses were used to determine the relationship between disease severity subgroup and treatment at the time of diagnosis. Results. In total, 125 children with AAV were studied. Severity subgroup was associated with treatment group in both the EUVAS (chi-square 45.14, p 〈 0.001, Kendall’s tau-b 0.601, p 〈 0.001) and WGET (chi-square 59.33, p 〈 0.001, Kendall’s tau-b 0.689, p 〈 0.001) systems; however, 7 children classified by both systems as having less severe disease received CYC, and 6 children classified as having severe disease by both systems did not receive CYC. Conclusion. In this pediatric AAV cohort, the EUVAS and WGET adult severity subclassification systems had strong correlation with physician choice of treatment. However, a proportion of patients received treatment that was not concordant with their assigned severity subclass.
    Type of Medium: Online Resource
    ISSN: 0315-162X , 1499-2752
    URL: Article
    DOI: 10.3899/jrheum.120299
    RVK:
    XA 10000
    Language: English
    Publisher: The Journal of Rheumatology
    Publication Date: 2012
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