67 results on '"Son, Mary Beth F."'
Search Results
2. Racial Disparities and Achievement of the Low Lupus Disease Activity State: A CARRA Registry Study.
- Author
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Soulsby WD, Olveda R, He J, Berbert L, Weller E, Barbour KE, Greenlund KJ, Schanberg LE, von Scheven E, Hersh A, Son MBF, Chang J, and Knight A
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- Adolescent, Child, Female, Humans, Male, Black or African American, Health Status Disparities, Hispanic or Latino, Prednisone therapeutic use, Race Factors, Severity of Illness Index, Social Determinants of Health ethnology, United States epidemiology, White, Asian, Lupus Erythematosus, Systemic ethnology, Lupus Erythematosus, Systemic drug therapy, Registries
- Abstract
Objective: Differential disease control may contribute to racial disparities in outcomes of childhood-onset systemic lupus erythematosus (cSLE). We evaluated associations of race and individual- or neighborhood-level social determinants of health (SDoH) with achievement of low lupus disease activity state (LLDAS), a clinically relevant treatment target., Methods: In this cSLE cohort study using the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry, the primary exposure was self-reported race and ethnicity, and collected SDoH included insurance status and area deprivation index (ADI). Outcomes included LLDAS, disease activity, and time-averaged prednisone exposure. Associations among race and ethnicity, SDoH, and disease activity were estimated with multivariable regression models, adjusting for disease-related and demographic factors., Results: Among 540 children with cSLE, 27% identified as Black, 25% identified as White, 23% identified as Latino/a, 11% identified as Asian, 9% identified as more than one race, and 5% identified as other. More Black children (41%) lived in neighborhoods of highest ADI compared to White children (16%). Black race was associated with lower LLDAS achievement (adjusted odds ratio 0.56, 95% confidence interval [CI] 0.38-0.82) and higher disease activity (adjusted β 0.94, 95% CI 0.11-1.78). The highest ADI was not associated with lower LLDAS achievement on adjustment for renal disease and insurance. However, renal disease was found to be a significant mediator (P = 0.04) of the association between ADI and prednisone exposure., Conclusions: Children with cSLE who identified as Black are less likely to achieve LLDAS and have a higher disease activity. Living in areas of higher ADI may relate to renal disease and subsequent prednisone exposure. Strategies to address root causes will be important to design interventions mitigating cSLE racial disparities., (© 2024 The Author(s). Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.) more...
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- 2025
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3. Features of hyperinflammation link the biology of EBV infection and cytokine storm syndromes.
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Liu M, Brodeur KE, Bledsoe JR, Harris CN, Joerger J, Weng R, Hsu EE, Lam MT, Rimland CA, LeSon CE, Yue J, Henderson LA, Dedeoglu F, Newburger JW, Nigrovic PA, Son MBF, and Lee PY
- Abstract
Background: Overt immune activation by viral infections can lead to cytokine storm syndromes, such as hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS)., Objective: We aim to compare the immune response to different viral pathogens to understand the connection between infections and cytokine storm syndromes., Methods: We recruited children who presented to the emergency room with fever for ≥ 3 days. We performed immune profiling using Olink proximity extension assay and flow cytometry. We compared the findings with cases of HLH, MAS, Kawasaki disease (KD), and multisystem inflammatory syndrome in children (MIS-C)., Results: We enrolled 352 febrile patients and studied 110 cases with confirmed common viral infections. We found that Epstein-Barr virus (EBV) uniquely triggered high levels of multiple cytokines (IL-18, IL-27, tumor necrosis factor, FLT3 ligand, and lymphotoxin alpha) and IFN-γ-induced chemokines (CXCL9/10/11 and CCL19). These patterns are similar to the hyperinflammatory response associated with HLH / MAS, but less consistent with the findings in KD and MIS-C. Flow cytometry analysis revealed that CD38
+ HLA-DR+ T lymphocytes, which are pathogenic cells responsible for IFN-γ production in HLH / MAS, are vastly expanded in patients with acute EBV infection. Cell sorting identified CD38+ HLA-DR+ T cells as atypical lymphocytes that are classically associated with acute EBV infection., Conclusion: This work broadens our understanding of common viral infections in children and provides an immunologic basis for the link between EBV infection and HLH / MAS., (Copyright © 2024. Published by Elsevier Inc.) more...- Published
- 2024
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4. Kawasaki disease: contemporary perspectives.
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Day-Lewis M, Son MBF, and Lo MS
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- Humans, Infant, Child, Preschool, Immunoglobulins, Intravenous therapeutic use, Biomarkers blood, Child, Risk Factors, Mucocutaneous Lymph Node Syndrome diagnosis, Mucocutaneous Lymph Node Syndrome therapy, Mucocutaneous Lymph Node Syndrome complications, Coronary Aneurysm diagnosis, Coronary Aneurysm etiology
- Abstract
Kawasaki disease is a paediatric vasculitis that presents with fever, rash, conjunctivitis, mucositis, lymphadenopathy, and extremity changes, and primarily affects children younger than 5 years. Coronary artery aneurysms are observed in approximately 20% of patients without treatment. Giant coronary artery aneurysms are rare but can result in substantial morbidity and mortality due to the risk of thrombosis, stenosis, and myocardial infarction. Infants younger than 6 months and children with coronary artery abnormalities are at highest risk for the development of large or giant coronary artery aneurysms, necessitating swift identification and aggressive treatment. The children at high risk for coronary artery aneurysms warrant primary intensification therapy; however, what the most optimal adjunct therapy might be to reduce their risk is unclear and large-scale international trials are needed. Kawasaki disease is a clinical diagnosis that shares many features with other common febrile illnesses, including multisystem inflammatory syndrome in children. Identifying biomarkers that can distinguish Kawasaki disease from similar conditions and predict coronary artery aneurysm risk are needed to aid timely diagnosis, guide management, and improve patient outcomes., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.) more...
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- 2024
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5. Real-world application of the pediatric Glucocorticoid Toxicity Index in childhood-onset lupus.
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Zhang E, Capponi S, Scobell R, Alonzi G, Hlobik M, Daga A, Meidan E, Wobma H, Kim L, Henderson LA, Case S, Nigrovic PA, Stone JH, Costenbader KH, Son MBF, and Chang JC
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- Humans, Female, Male, Child, Retrospective Studies, Adolescent, Age of Onset, Risk Factors, Feasibility Studies, Lupus Erythematosus, Systemic drug therapy, Glucocorticoids adverse effects, Glucocorticoids administration & dosage, Glucocorticoids therapeutic use
- Abstract
Objectives: The pediatric Glucocorticoid Toxicity Index (pGTI) is a new, pediatric-specific tool to quantify glucocorticoid (GC)-related morbidity in children. We evaluated the feasibility and construct validity of retrospective pGTI scoring in patients with pediatric-onset systemic lupus erythematosus (pSLE) and identified risk factors for cumulative toxicity., Methods: We conducted a retrospective cohort study of patients with pSLE treated with GCs at two pediatric centers (1999-2023). GC exposure was estimated using interval-averaged oral prednisone-equivalent dose and cumulative prednisone-equivalent dose. We scored change in GC toxicity every 6 months (±2) using a modified pGTI including 7 of 10 domains. We calculated the Cumulative Worsening Score (CWS), a continuous summation of toxicity accrued. Mixed effects linear regression was used to identify factors associated with CWS., Results: There were 126 patients with pSLE, including 88 with nephritis, with a median of 6 visits/patient. Nearly half (47 %) experienced toxicity in the Blood Pressure domain. Other common toxicities were mood disturbance (25 %), followed by increased body mass index (BMI), striae, and sleep disturbance (21 % each). Decreased growth velocity was observed in 18 %. There was modest correlation between cumulative GC dose and CWS (rho 0.3; p < 0.01). Greater cumulative toxicity was associated with younger age, elevated BMI, and rituximab use at the time of GC initiation, albeit indications for the latter were not captured., Conclusions: Patients with pSLE experience a high burden of GC toxicity, particularly related to blood pressure, BMI, sleep, and growth. Standardized, pediatric-specific GC toxicity assessment is feasible in real-world settings and can facilitate evaluation of strategies to reduce morbidity in children requiring chronic GC treatment., Competing Interests: Declaration of competing interest J.C.C previously received grant funding from GSK for investigator-driven research outside the scope of this work. Professor Stone's hospital, the Massachusetts General Hospital, owns the intellectual property of the pGTI. The worldwide licensing rights to the pGTI are controlled by Steritas, LLC. Professor Stone co-founded Steritas and is the chair of the Scientific Advisory Board but has no fiduciary responsibility at the company. The remaining co-authors have no other relevant financial conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier Inc.) more...
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- 2024
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6. Severe Features of Systemic Juvenile Idiopathic Arthritis in Patients With Congenital Heart Disease.
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Aires BP, Wobma H, Samad A, Chandler MT, Chang MH, Dedeoglu F, Fishman MP, Klouda T, Levin J, Halyabar O, Saleeb SF, Tworetzky W, Son MBF, Newburger JW, Casey A, and Henderson LA
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- Humans, Male, Female, Retrospective Studies, Child, Preschool, Child, Infant, Macrophage Activation Syndrome etiology, Macrophage Activation Syndrome complications, Risk Factors, Severity of Illness Index, Adolescent, Arthritis, Juvenile complications, Heart Defects, Congenital complications
- Abstract
Objective: To describe the clinical features of patients with congenital heart disease (CHD) who subsequently developed systemic juvenile idiopathic arthritis (sJIA)., Methods: We conducted a retrospective review of patients diagnosed with CHD and sJIA at our institution. Detailed clinical, laboratory, and radiographic data were collected from the medical record and reviewed with each patient's primary medical team., Results: Five patients with sJIA and CHD were identified. Each child had a unique cardiac anatomy, but all the patients required surgical repair during the first year of life. Four children had thymectomies at the time of cardiac surgery. Classic signs of sJIA such as fever (n = 5), rash (n = 5), and arthritis (n = 4) developed after surgical intervention in all the patients. The individuals in this cohort displayed risk factors associated with severe sJIA, including disease onset before 2 years of age (n = 5), elevated interleukin 18 levels (n = 5), baseline eosinophilia prior to initiation of biologic disease-modifying antirheumatic drugs (n = 4), and positivity for HLA-DRB1*15:01 alleles (n = 4). Macrophage activation syndrome (MAS) occurred in 3 patients and sJIA-associated lung disease (sJIA-LD) was identified in 4 patients. Two children died from complications of their cardiac and/or pulmonary disease., Conclusion: We identified an association between CHD and severe forms of sJIA. Although these findings will need to be confirmed in larger, multicenter cohorts, the results highlight the importance of considering a diagnosis of sJIA in children with CHD and remaining vigilant for complications such as MAS and sJIA-LD., (Copyright © 2024 by the Journal of Rheumatology.) more...
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- 2024
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7. Racial and Ethnic Composition of Populations Served by Freestanding Children's Hospitals and Disparities in Outcomes of Pediatric Lupus.
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Chang JC, Liu JP, Berbert LM, Chandler MT, Patel PN, Smitherman EA, Weller EA, Son MBF, and Costenbader KH
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- Adolescent, Adult, Child, Child, Preschool, Female, Humans, Male, Young Adult, Black or African American, Health Status Disparities, Hispanic or Latino statistics & numerical data, Retrospective Studies, United States epidemiology, White People, Healthcare Disparities ethnology, Hospitals, Pediatric, Lupus Erythematosus, Systemic ethnology, Lupus Erythematosus, Systemic therapy, Lupus Erythematosus, Systemic diagnosis
- Abstract
Objective: Health disparities may be driven by hospital-level factors. We assessed whether racial and ethnic composition of populations hospitals serve explain or modify disparities in hospital outcomes of children with systemic lupus erythematosus (SLE)., Methods: In this retrospective cohort study of patients 5 to 26 years old with SLE at 47 children's hospitals in the Pediatric Health Information System (2006-2021), race and ethnicity were assessed at the patient level and hospital level (proportion of total admissions composed of Black or Hispanic patients, respectively). Outcomes included intensive care unit (ICU) admission or adverse renal outcome (end-stage renal disease, dialysis, or transplant) during follow-up. We estimated racial and ethnic disparities, adjusted or stratified by hospital racial or ethnic composition., Results: Of 8,125 patients with SLE, 2,293 (28%) required ICU admission, and 698 (9%) had an adverse renal outcome. Black and non-Hispanic White disparities in ICU admission were observed only at hospitals serving higher proportions of Black patients (odds ratio [OR] 1.29, 95% confidence interval [95% CI] 1.04-1.59 vs OR 1.07, 95% CI 0.83-1.38). Larger Black and non-Hispanic White disparities in adverse renal outcomes were observed at hospitals with higher Black racial composition (OR 2.0, 95% CI 1.4-2.8 vs OR 1.7, 95% CI 1.1-2.4). Conversely, Hispanic versus non-Hispanic disparities in renal outcomes persisted after adjustment for hospital-reported Hispanic ethnic composition but were observed only at hospitals with lower proportions of Hispanic patients., Conclusion: Worse Black and White disparities in SLE outcomes are observed at children's hospitals serving more Black children, whereas distinct patterns are observed for Hispanic and non-Hispanic disparities. Reporting of hospital characteristics related to populations served is needed to identify modifiable drivers of hospital-level variation., (© 2024 American College of Rheumatology.) more...
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- 2024
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8. The RECOVERY trial of PIMS-TS: important lessons from the pandemic.
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Son MBF and Randolph AG
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- Humans, Systemic Inflammatory Response Syndrome, Pandemics, COVID-19 complications
- Abstract
Competing Interests: MBFS declares grants from the US Centers for Disease Control and Prevention (CDC) and royalties from UpToDate for being an author on the section for MIS-C. AGR declares grants from the US National Institutes of Health (NIH) and US CDC to her institution; is the section editor of paediatric critical care medicine of UpToDate; honoraria for Grand Rounds presentation from St. Jude; honoraria from ThermoFisher; travel support from the International Sepsis Forum, Institut Merieux, and ThermoFisher; participation on data safety monitoring boards of the NIH Grace Study, REMAP-CAP, and NIH PREVENT-VILI; is on the medical advisory board of Families Fighting Flu; chairs the International Sepsis Forum; and has received reagents from Illumina. more...
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- 2024
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9. Underutilization of ambulatory blood pressure monitoring in locally and nationally representative samples of patients with childhood-onset systemic lupus erythematosus.
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Chang JC, Son MBF, Alonzi G, Weiss PF, and Daga A
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- Humans, Child, Case-Control Studies, Age of Onset, Blood Pressure Monitoring, Ambulatory, Lupus Erythematosus, Systemic
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- 2024
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10. Updated Case Definition of MIS-C and Implications for Clinical Care.
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Day-Lewis M, Berbert L, Baker A, Dionne A, Newburger JW, and Son MBF
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- Humans, Child, Retrospective Studies, Systemic Inflammatory Response Syndrome, COVID-19, Mucocutaneous Lymph Node Syndrome
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Objectives: A broad, surveillance case definition was implemented when multisystem inflammatory syndrome in children (MIS-C) emerged in 2020. In 2023, a revised MIS-C case definition was constructed to improve specificity and reduce misclassification with other pediatric inflammatory conditions. This study aims to describe the impact of the updated definition on the classification of patients with MIS-C and Kawasaki Disease (KD)., Methods: Patients hospitalized from March 2020 to November 2022 with clinician-diagnosed KD and MIS-C at a single center were studied retrospectively. Specificity and positive predictive value were assessed; McNemar test was used to compare specificity., Results: Among 119 patients with MIS-C per the 2020 definition, 20 (17%) did not fulfill the 2023 definition. Six of these 20 (30%) had shock or cardiac involvement. Of 59 KD patients, 10 (17%) met the 2020 MIS-C definition. Five patients (8%) met the 2023 MIS-C definition. Specificity for the 2020 and 2023 MIS-C definitions among KD patients were 83.1% and 91.5% respectively (McNemar, P = .0736). Positive predictive value was higher for the 2023 MIS-C case definition compared with the 2020 MIS-C case definition (95.2% vs 92.2%)., Conclusions: Approximately 1 in 5 patients diagnosed with MIS-C using the 2020 case definition did not meet the 2023 definition, including patients with cardiovascular dysfunction. Overlap persisted between patients meeting KD and 2023 MIS-C case definitions, with a false positive rate of 8%. Implications for treatment should be considered, particularly in settings where presumed MIS-C may be treated with corticosteroid monotherapy., (Copyright © 2024 by the American Academy of Pediatrics.) more...
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- 2024
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11. Health Equity Implications of Missing Data Among Youths With Childhood-Onset Systemic Lupus Erythematosus: A Proof-of-Concept Study in the Childhood Arthritis and Rheumatology Research Alliance Registry.
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Woo JMP, Simmonds F, Dennos A, Son MBF, Lewandowski LB, and Rubinstein TB
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- Child, Humans, Adolescent, Registries, Severity of Illness Index, Arthritis, Juvenile diagnosis, Arthritis, Juvenile epidemiology, Arthritis, Juvenile complications, Health Equity, Rheumatology, Lupus Erythematosus, Systemic diagnosis, Lupus Erythematosus, Systemic epidemiology, Lupus Erythematosus, Systemic therapy
- Abstract
Objective: Health disparities in childhood-onset systemic lupus erythematosus (SLE) disproportionately impact marginalized populations. Socioeconomically patterned missing data can magnify existing health inequities by supporting inferences that may misrepresent populations of interest. Our objective was to assess missing data and subsequent health equity implications among participants with childhood-onset SLE enrolled in a large pediatric rheumatology registry., Methods: We evaluated co-missingness of 12 variables representing demographics, socioeconomic position, and clinical factors (e.g., disease-related indices) using Childhood Arthritis and Rheumatology Research Alliance Registry childhood-onset SLE enrollment data (2015-2022; n = 766). We performed logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) for missing disease-related indices at enrollment (Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2K] and/or Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI]) associated with data missingness. We used linear regression to assess the association between socioeconomic factors and SLEDAI-2K at enrollment using 3 analytic methods for missing data: complete case analysis, multiple imputation, and nonprobabilistic bias analyses, with missing values imputed to represent extreme low or high disadvantage., Results: On average, participants were missing 6.2% of data, with over 50% of participants missing at least 1 variable. Missing data correlated most closely with variables within data categories (i.e., demographic). Government-assisted health insurance was associated with missing SLEDAI-2K and/or SDI scores compared to private health insurance (OR 2.04 [95% CI 1.22, 3.41]). The different analytic approaches resulted in varying analytic sample sizes and fundamentally conflicting estimated associations., Conclusion: Our results support intentional evaluation of missing data to inform effect estimate interpretation and critical assessment of causal statements that might otherwise misrepresent health inequities., (© 2023 American College of Rheumatology. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.) more...
- Published
- 2023
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12. Incidence and Risk Factors for Eosinophilia and Lung Disease in Biologic-Exposed Children With Systemic Juvenile Idiopathic Arthritis.
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Wobma H, Arvila SR, Taylor ML, Lam KP, Ohashi M, Gebhart C, Powers H, Case S, Chandler MT, Chang MH, Cohen E, Day-Lewis M, Fishman MP, Halyabar O, Hausmann JS, Hazen MM, Lee PY, Lo MS, Meidan E, Roberts JE, Son MBF, Sundel RP, Dedeoğlu F, Nigrovic PA, Casey A, Chang J, and Henderson LA more...
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- Humans, Child, Incidence, Retrospective Studies, Interleukin-6 Inhibitors, Risk Factors, Interleukin-1, Arthritis, Juvenile diagnosis, Arthritis, Juvenile drug therapy, Arthritis, Juvenile epidemiology, Lung Diseases, Eosinophilia chemically induced, Eosinophilia diagnosis, Eosinophilia epidemiology, Biological Products therapeutic use
- Abstract
Objective: Although interleukin-1 (IL-1)/IL-6 inhibitors are effective therapies for systemic juvenile idiopathic arthritis (JIA), some patients develop eosinophilia and lung disease during treatment. This study was undertaken to retrospectively evaluate incidence and risk factors for eosinophilia and describe lung disease outcomes in IL-1/IL-6 inhibitor-exposed patients with systemic JIA., Methods: Among JIA patients at our institution exposed to interleukin-1 (IL-1)/IL-6 inhibitors (1995-2022), we compared incidence rate of eosinophilia in systemic JIA compared to other JIA, stratified by medication class (IL-1/IL-6 inhibitors, other cytokine inhibitors, methotrexate). We used Cox models to identify predictors of eosinophilia during IL-1/IL-6 inhibitor use and summarized treatment changes and outcomes after eosinophilia, including lung disease. HLA typing was performed on a clinical or research basis., Results: There were 264 new medication exposures in 75 patients with systemic JIA and 41 patients with other JIA. A total of 49% of patients with systemic JIA with HLA typing (n = 45) were positive for HLA-DRB1*15 alleles. Eosinophilia was common during IL-1/IL-6 inhibitor use and did not differ by systemic JIA compared to other JIA (0.08 and 0.07 per person-year, respectively; P = 0.30). Among systemic JIA patients, pretreatment macrophage activation syndrome (MAS) was associated with a higher rate of subsequent eosinophilia on biologic therapy (unadjusted hazard ratio 3.2 [95% confidence interval 1.2-8.3]). A total of 4 of 5 patients who switched therapy within 10 weeks of eosinophilia experienced disease flare compared to none of the patients who continued the original therapy. A total of 8 of 25 patients with pulmonary evaluations had lung disease, and all had severe manifestations of systemic JIA (MAS, intensive care unit stay). One death was attributed to systemic JIA-lung disease., Conclusion: Eosinophilia is common in JIA patients using IL-1/IL-6 inhibitors. Severe disease may be associated with eosinophilia and lung disease in systemic JIA., (© 2023 American College of Rheumatology.) more...
- Published
- 2023
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13. Development of a Screening Algorithm for Lung Disease in Systemic Juvenile Idiopathic Arthritis.
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Wobma H, Bachrach R, Farrell J, Chang MH, Day-Lewis M, Dedeoglu F, Fishman MP, Halyabar O, Harris C, Ibanez D, Kim L, Klouda T, Krone K, Lee PY, Lo MS, McBrearty K, Meidan E, Prockop SE, Samad A, Son MBF, Nigrovic PA, Casey A, Chang JC, and Henderson LA more...
- Abstract
Objective: Lung disease (LD) is an increasingly recognized complication of systemic juvenile idiopathic arthritis (sJIA). As there are no currently available guidelines for pulmonary screening in sJIA, we sought to develop such an algorithm at our institution., Methods: A multidisciplinary workgroup was convened, including members representing rheumatology, pulmonary, stem cell transplantation, and patient families. The workgroup leaders drafted an initial algorithm based on published literature and experience at our center. A modified Delphi approach was used to achieve agreement through three rounds of anonymous, asynchronous voting and a consensus meeting. Statements approved by the workgroup were rated as appropriate with moderate or high levels of consensus. These statements were organized into the final approved screening algorithm for LD in sJIA., Results: The workgroup ultimately rated 20 statements as appropriate with a moderate or high level of consensus. The approved algorithm recommends pulmonary screening for newly diagnosed patients with sJIA with clinical features that the workgroup agreed may confer increased risk for LD. These "red flag features" include baseline characteristics (young age of sJIA onset, human leukocyte antigen type, trisomy 21), high disease activity (macrophage activation syndrome [MAS], sJIA-related ICU admission, elevated MAS biomarkers), respiratory symptoms or abnormal pulmonary examination findings, and features of drug hypersensitivity-like reactions (eosinophilia, atypical rash, anaphylaxis). The workgroup achieved consensus on the recommended pulmonary work-up and monitoring guidelines., Conclusion: We developed a pulmonary screening algorithm for sJIA-LD through a multidisciplinary consensus-building process, which will be revised as our understanding of sJIA-LD continues to evolve., (© 2023 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.) more...
- Published
- 2023
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14. A case of neonatal sweet syndrome associated with mevalonate kinase deficiency.
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Irwin M, Tanawattanacharoen VK, Turner A, Son MBF, Hale RC, Platt CD, Putra J, Schmidt BAR, and Wasserman MG
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- Adult, Humans, Infant, Newborn, Inflammatory Bowel Diseases, Mevalonate Kinase Deficiency complications, Mevalonate Kinase Deficiency diagnosis, Sweet Syndrome diagnosis, Sweet Syndrome drug therapy, Sweet Syndrome etiology
- Abstract
Background: Sweet syndrome (SS), also known as acute febrile neutrophilic dermatosis, is an immunologic syndrome characterized by widespread neutrophilic infiltration. Histiocytoid Sweet syndrome (H-SS) is a histopathologic variant of SS. While SS most commonly occurs in adults, this case report discusses an infant patient who presented with H-SS., Case Presentation: Through a multidisciplinary approach, this patient was also found to have very early onset inflammatory bowel disease (VEO-IBD) and Mevalonate kinase-associated disease (MKAD). While prior case studies have characterized an association between VEO-IBD and MKAD, there is no literature describing the association of all three diagnoses this case: H-SS, VEO-IBD and MKAD. Initiation of canakinumab in this patient resulted in successful control of the disease., Conclusions: This case highlights the importance of a multidisciplinary approach to rare diagnoses, and collaboration during cases with significant diagnostic uncertainty., (© 2023. BioMed Central Ltd., part of Springer Nature.) more...
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- 2023
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15. Real-world use and outcomes of belimumab in childhood-onset lupus: A single-center retrospective study.
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Roberts JE, Burn C, Sadun RE, Smitherman EA, Wenderfer SE, and Son MBF
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- Young Adult, Humans, Child, Prednisone therapeutic use, Glucocorticoids therapeutic use, Immunosuppressive Agents adverse effects, Retrospective Studies, Severity of Illness Index, Treatment Outcome, Lupus Erythematosus, Systemic drug therapy, Lupus Erythematosus, Systemic chemically induced
- Abstract
Background: Studies of real-world effectiveness of belimumab in adults with systemic lupus erythematosus have shown improved disease control and decreased oral glucocorticoid use. However, belimumab use outside of clinical trial settings has not been well studied in childhood-onset systemic lupus erythematosus (cSLE). We aimed to characterize indications for belimumab use and evaluate oral glucocorticoid doses and disease activity scores in the year following belimumab initiation at a single, large pediatric rheumatology center., Methods: We included children and young adults with cSLE who received ≥ 1 dose of belimumab. Repeated measures one-way ANOVA was used to compare SLEDAI-2K scores and prednisone-equivalent daily oral glucocorticoid doses at baseline, 6 months, and 12 months after belimumab initiation for those who continued therapy for a year., Results: We identified 21 patients with cSLE who received ≥ 1 dose of belimumab. The median disease duration at belimumab initiation was 30.8 months [IQR 21.0-79.1]. At the time of belimumab initiation, 100% of patients were taking an antimalarial, 81% were on oral glucocorticoids, and 91% were on at least one conventional DMARD. Thirteen patients (62%) continued belimumab for ≥6 months and 11 (52%) for ≥12 months. Among those continuing belimumab for ≥12 months, median [IQR] oral prednisone daily doses in milligrams at baseline, 6 months, and 12 months were 12.5 [7.5-17.5], 9 [6.25-10], and 5 [5-9.5], p = 0.037, and median [IQR] SLEDAI-2K scores at baseline, 6 months, and 12 months were 8 [5.5-10.5], 6 [3.5-10], and 6 [6-8.5], p = 0.548, respectively., Conclusions: In our cohort of pediatric patients with lupus and moderate disease activity treated with belimumab for ≥12 months, daily oral glucocorticoid doses were significantly lower 6 and 12 months after belimumab initiation than baseline. Use in patients with active nephritis was uncommon. Further research is needed in a large, multicenter cohort to determine the real-world effectiveness of belimumab in children and develop guidelines for use. more...
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- 2023
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16. Insurance Status and Tumor Necrosis Factor Inhibitor Initiation Among Children With Juvenile Idiopathic Arthritis in the CARRA Registry.
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Roberts JE, Williams K, Dallas J, Eckert M, Huie L, Smitherman E, Soulsby WD, Zhao Y, and Son MBF
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- Humans, Child, Tumor Necrosis Factor Inhibitors therapeutic use, Retrospective Studies, Insurance Coverage, Registries, Arthritis, Juvenile diagnosis, Rheumatology, Antirheumatic Agents therapeutic use
- Abstract
Objective: Prompt escalation to tumor necrosis factor inhibitors (TNFis) is recommended for children with juvenile idiopathic arthritis (JIA) and ongoing disease activity despite treatment with conventional disease-modifying antirheumatic drugs (cDMARDs). It is unknown whether these recommendations are equitably followed for children with different insurance types. We assessed the association of insurance coverage on the odds and timing of TNFi use., Methods: We conducted a retrospective study of children with newly diagnosed JIA in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. We compared the odds of starting a TNFi in the first year and time from cDMARD to TNFi initiation between those with public and private insurance., Results: We identified 1086 children with new JIA diagnoses. Publicly insured children had significantly higher active joint counts and parent/patient global assessment scores at the enrollment visit. They were also more likely to have polyarticular arthritis compared to those with private insurance. Odds of any TNFi use in the first year did not differ between publicly and privately insured children. Publicly insured children were escalated from cDMARD to TNFi more quickly than privately insured children., Conclusion: Children who were publicly insured had more severe disease and polyarticular involvement at registry enrollment compared to those who were privately insured. Whereas overall TNFi use did not differ between children with different insurance types, publicly insured children were escalated more quickly, consistent with their increased disease severity. Further research is needed to determine why insurance coverage type is associated with disease severity, including how other socioeconomic factors affect presentation to care., (Copyright © 2023 by the Journal of Rheumatology.) more...
- Published
- 2023
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17. Variation in Early Anakinra Use and Short-Term Outcomes in Multisystem Inflammatory Syndrome in Children.
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Chang JC, Young CC, Muscal E, Sexson Tejtel SK, Newhams MM, Kucukak S, Crandall H, Maddux AB, Rowan CM, Halasa NB, Harvey HA, Hobbs CV, Hall MW, Kong M, Aguiar CL, Schuster JE, Fitzgerald JC, Singh AR, Wellnitz K, Nofziger RA, Cvijanovich NZ, Mack EH, Schwarz AJ, Heidemann SM, Newburger JW, Zambrano LD, Campbell AP, Patel MM, Randolph AG, and Son MBF more...
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- Child, Humans, Immunoglobulins, Intravenous therapeutic use, C-Reactive Protein, Stroke Volume, Retrospective Studies, Ventricular Function, Left, Glucocorticoids therapeutic use, Interleukin 1 Receptor Antagonist Protein therapeutic use, Connective Tissue Diseases
- Abstract
Objective: Evidence regarding effectiveness of interleukin-1 receptor antagonism in multisystem inflammatory syndrome in children (MIS-C) is lacking. We characterized variation in initial treatment with anakinra and evaluated cardiovascular outcomes associated with adding anakinra to standard initial therapy., Methods: We conducted a retrospective cohort study of MIS-C cases in a US surveillance registry from November 2020 to December 2021. Day 0 was the first calendar day of immunomodulatory treatment. Factors associated with initial anakinra use (days 0-1) were identified. We compared cases in patients ages 2-20 years receiving intravenous immunoglobulin (IVIG) and glucocorticoids versus anakinra plus IVIG and/or glucocorticoids on days 0-1, using inverse probability weighting to balance disease severity. Primary outcomes were vasopressor requirement on day 3 and impaired left ventricular ejection fraction on days 3-4. The secondary outcome was 50% reduction in C-reactive protein on day 3., Results: Among 1,516 MIS-C cases at 44 sites, 193 (13%) patients received anakinra alone or with other immunomodulators as initial treatment (range 0-74% by site). Site accounted for 59% of residual variance in anakinra use. After balancing disease severity, initial treatment with anakinra plus IVIG and/or glucocorticoids (n = 121) versus IVIG plus glucocorticoids (n = 389) was not associated with significant differences in vasopressor requirement (25.6% versus 20.1%, respectively; risk ratio [RR] 1.27 [95% confidence interval (95% CI) 0.88-1.84]), ventricular dysfunction (33.7% versus 25.7%, respectively; RR 1.31 [95% CI 0.98-1.75]), or C-reactive protein reduction., Conclusion: We identified substantial variation in initial anakinra use in a real-world population of children with MIS-C, but no average short-term improvement in cardiovascular outcomes associated with early addition of anakinra to IVIG and/or glucocorticoids compared to IVIG and glucocorticoids alone., (© 2023 American College of Rheumatology.) more...
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- 2023
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18. Neurological and Psychological Sequelae Associated With Multisystem Inflammatory Syndrome in Children.
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Rollins CK, Calderon J, Wypij D, Taylor AM, Davalji Kanjiker TS, Rohde JS, Maiman M, Zambrano LD, Newhams MM, Rodriguez S, Hart N, Worhach J, Kucukak S, Poussaint TY, Son MBF, Friedman ML, Gertz SJ, Hobbs CV, Kong M, Maddux AB, McGuire JL, Licht PA, Staat MA, Yonker LM, Mazumdar M, Randolph AG, Campbell AP, and Newburger JW more...
- Subjects
- United States, Child, Female, Humans, Cross-Sectional Studies, Cohort Studies, Systemic Inflammatory Response Syndrome, Disease Progression, Quality of Life, Connective Tissue Diseases
- Abstract
Importance: Acute neurological involvement occurs in some patients with multisystem inflammatory syndrome in children (MIS-C), but few data report neurological and psychological sequelae, and no investigations include direct assessments of cognitive function 6 to 12 months after discharge., Objective: To characterize neurological, psychological, and quality of life sequelae after MIS-C., Design, Setting, and Participants: This cross-sectional cohort study was conducted in the US and Canada. Participants included children with MIS-C diagnosed from November 2020 through November 2021, 6 to 12 months after hospital discharge, and their sibling or community controls, when available. Data analysis was performed from August 2022 to May 2023., Exposure: Diagnosis of MIS-C., Main Outcomes and Measures: A central study site remotely administered a onetime neurological examination and in-depth neuropsychological assessment including measures of cognition, behavior, quality of life, and daily function. Generalized estimating equations, accounting for matching, assessed for group differences., Results: Sixty-four patients with MIS-C (mean [SD] age, 11.5 [3.9] years; 20 girls [31%]) and 44 control participants (mean [SD] age, 12.6 [3.7] years; 20 girls [45%]) were enrolled. The MIS-C group exhibited abnormalities on neurological examination more frequently than controls (15 of 61 children [25%] vs 3 of 43 children [7%]; odds ratio, 4.7; 95% CI, 1.3-16.7). Although the 2 groups performed similarly on most cognitive measures, the MIS-C group scored lower on the National Institutes of Health Cognition Toolbox List Sort Working Memory Test, a measure of executive functioning (mean [SD] scores, 96.1 [14.3] vs 103.1 [10.5]). Parents reported worse psychological outcomes in cases compared with controls, particularly higher scores for depression symptoms (mean [SD] scores, 52.6 [13.1] vs 47.8 [9.4]) and somatization (mean [SD] scores, 55.5 [15.5] vs 47.0 [7.6]). Self-reported (mean [SD] scores, 79.6 [13.1] vs 85.5 [12.3]) and parent-reported (mean [SD] scores, 80.3 [15.5] vs 88.6 [13.0]) quality of life scores were also lower in cases than controls., Conclusions and Relevance: In this cohort study, compared with contemporaneous sibling or community controls, patients with MIS-C had more abnormal neurologic examinations, worse working memory scores, more somatization and depression symptoms, and lower quality of life 6 to 12 months after hospital discharge. Although these findings need to be confirmed in larger studies, enhanced monitoring may be warranted for early identification and treatment of neurological and psychological symptoms. more...
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- 2023
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19. Immunomodulatory Therapy for MIS-C.
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Ouldali N, Son MBF, McArdle AJ, Vito O, Vaugon E, Belot A, Leblanc C, Murray NL, Patel MM, Levin M, Randolph AG, and Angoulvant F
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- Child, Humans, Stroke Volume, Ventricular Function, Left, Immunomodulation, Glucocorticoids therapeutic use, Immunoglobulins, Intravenous therapeutic use
- Abstract
Context: Studies comparing initial therapy for multisystem inflammatory syndrome in children (MIS-C) provided conflicting results., Objective: To compare outcomes in MIS-C patients treated with intravenous immunoglobulin (IVIG), glucocorticoids, or the combination thereof., Data Sources: Medline, Embase, CENTRAL and WOS, from January 2020 to February 2022., Study Selection: Randomized or observational comparative studies including MIS-C patients <21 years., Data Extraction: Two reviewers independently selected studies and obtained individual participant data. The main outcome was cardiovascular dysfunction (CD), defined as left ventricular ejection fraction < 55% or vasopressor requirement ≥ day 2 of initial therapy, analyzed with a propensity score-matched analysis., Results: Of 2635 studies identified, 3 nonrandomized cohorts were included. The meta-analysis included 958 children. IVIG plus glucocorticoids group as compared with IVIG alone had improved CD (odds ratio [OR] 0.62 [0.42-0.91]). Glucocorticoids alone group as compared with IVIG alone did not have improved CD (OR 0.57 [0.31-1.05]). Glucocorticoids alone group as compared with IVIG plus glucocorticoids did not have improved CD (OR 0.67 [0.24-1.86]). Secondary analyses found better outcomes associated with IVIG plus glucocorticoids compared with glucocorticoids alone (fever ≥ day 2, need for secondary therapies) and better outcomes associated with glucocorticoids alone compared with IVIG alone (left ventricular ejection fraction < 55% ≥ day 2)., Limitations: Nonrandomized nature of included studies., Conclusions: In a meta-analysis of MIS-C patients, IVIG plus glucocorticoids was associated with improved CD compared with IVIG alone. Glucocorticoids alone was not associated with improved CD compared with IVIG alone or IVIG plus glucocorticoids. more...
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- 2023
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20. Clinical Course Associated with Aseptic Meningitis Induced by Intravenous Immunoglobulin for the Treatment of Multisystem Inflammatory Syndrome in Children.
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Young CC, LaRovere KL, Newhams MM, Kucukak S, Gertz SJ, Maddux AB, Halasa NB, Crandall H, Kong M, Fitzgerald JC, Irby K, Randolph AG, Campbell AP, and Son MBF
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- Child, Humans, Administration, Intravenous, Disease Progression, Immunoglobulins, Intravenous therapeutic use, Meningitis, Aseptic diagnosis, Meningitis, Aseptic drug therapy
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Aseptic meningitis is a rare but potentially serious complication of intravenous immunoglobulin treatment. In this case series, meningitic symptoms following intravenous immunoglobulin initiation in patients with multisystem inflammatory syndrome were rare (7/2,086 [0.3%]). However, they required the need for additional therapy and/or readmission., (Copyright © 2023 Elsevier Inc. All rights reserved.) more...
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- 2023
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21. Failure of Risk Prediction Modeling for IVIG Resistance in Kawasaki Disease.
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Son MBF, Gauvreau K, and Newburger JW
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- Humans, Treatment Failure, Immunoglobulins, Intravenous therapeutic use, Mucocutaneous Lymph Node Syndrome drug therapy
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- 2023
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22. A New Definition for Multisystem Inflammatory Syndrome in Children.
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Son MBF, Burns JC, and Newburger JW
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- Child, Humans, Systemic Inflammatory Response Syndrome, COVID-19
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- 2023
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23. Disordered T cell-B cell interactions in autoantibody-positive inflammatory arthritis.
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Julé AM, Lam KP, Taylor M, Hoyt KJ, Wei K, Gutierrez-Arcelus M, Case SM, Chandler M, Chang MH, Cohen EM, Dedeoglu F, Halyabar O, Hausmann J, Hazen MM, Janssen E, Lo J, Lo MS, Meidan E, Roberts JE, Wobma H, Son MBF, Sundel RP, Lee PY, Sage PT, Chatila TA, Nigrovic PA, Rao DA, and Henderson LA more...
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- Humans, Autoantibodies, T-Lymphocytes, Helper-Inducer, B-Lymphocytes, Arthritis, Rheumatoid, Arthritis, Juvenile
- Abstract
T peripheral helper (Tph) cells, identified in the synovium of adults with seropositive rheumatoid arthritis, drive B cell maturation and antibody production in non-lymphoid tissues. We sought to determine if similarly dysregulated T cell-B cell interactions underlie another form of inflammatory arthritis, juvenile oligoarthritis (oligo JIA). Clonally expanded Tph cells able to promote B cell antibody production preferentially accumulated in the synovial fluid (SF) of oligo JIA patients with antinuclear antibodies (ANA) compared to autoantibody-negative patients. Single-cell transcriptomics enabled further definition of the Tph gene signature in inflamed tissues and showed that Tph cells from ANA-positive patients upregulated genes associated with B cell help to a greater extent than patients without autoantibodies. T cells that co-expressed regulatory T and B cell-help factors were identified. The phenotype of these Tph-like Treg cells suggests an ability to restrain T cell-B cell interactions in tissues. Our findings support the central role of disordered T cell-help to B cells in autoantibody-positive arthritides., Competing Interests: PN has been supported by investigator-initiated research grants from Bristol-Myers Squibb BMS and Pfizer; consulting from BMS, Cerecor, Miach Orthopedics, Novartis, Pfizer, Quench Bio, Sigilon, Simcere, Sobi, and XBiotech; royalties from UpToDate Inc and the American Academy of Pediatrics.; and salary support from CARRA. DR reports personal fees from Pfizer, Janssen, Merck, Scipher Medicine, GlaxoSmithKline, and BMS and grant support from Janssen, Merck, and BMS, outside the submitted work. DR is a co-inventor on a patent application on Tph cells. LH has received salary support from CARRA; consulting fees from Sobi, Pfizer, and Adaptive Biotechnologies; and investigator-initiated research grants from Bristol-Myers Squibb. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Julé, Lam, Taylor, Hoyt, Wei, Gutierrez-Arcelus, Case, Chandler, Chang, Cohen, Dedeoglu, Halyabar, Hausmann, Hazen, Janssen, Lo, Lo, Meidan, Roberts, Wobma, Son, Sundel, Lee, Sage, Chatila, Nigrovic, Rao and Henderson.) more...
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- 2023
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24. SARS-CoV-2-Related Mitigation Measures and Insights Into Kawasaki Disease.
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Son MBF and Newburger JW
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- Humans, SARS-CoV-2, Mucocutaneous Lymph Node Syndrome, COVID-19
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- 2022
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25. Postdischarge Glucocorticoid Use and Clinical Outcomes of Multisystem Inflammatory Syndrome in Children.
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Son MBF, Berbert L, Young C, Dallas J, Newhams M, Chen S, Ardoin SP, Basiaga ML, Canny SP, Crandall H, Dhakal S, Dhanrajani A, Sagcal-Gironella ACP, Hobbs CV, Huie L, James K, Jones M, Kim S, Lionetti G, Mannion ML, Muscal E, Prahalad S, Schulert GS, Tejtel KS, Villacis-Nunez DS, Wu EY, Zambrano LD, Campbell AP, Patel MM, and Randolph AG more...
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- Child, Humans, Male, Female, Pandemics, Patient Discharge, Glucocorticoids therapeutic use, Retrospective Studies, Stroke Volume, Aftercare, Ventricular Function, Left, Weight Gain, Pneumonia, Viral epidemiology, Hyperglycemia
- Abstract
Importance: Minimal data are available regarding the postdischarge treatment of multisystem inflammatory syndrome in children (MIS-C)., Objectives: To evaluate clinical characteristics associated with duration of postdischarge glucocorticoid use and assess postdischarge clinical course, laboratory test result trajectories, and adverse events in a multicenter cohort with MIS-C., Design, Setting, and Participants: This retrospective cohort study included patients with MIS-C hospitalized with severe illness and followed up for 3 months in an ambulatory setting. Patients younger than 21 years who were admitted between May 15, 2020, and May 31, 2021, at 13 US hospitals were included. Inclusion criteria were inpatient treatment comprising intravenous immunoglobulin, diagnosis of cardiovascular dysfunction (vasopressor requirement or left ventricular ejection fraction ≤55%), and availability of complete outpatient data for 3 months., Exposures: Glucocorticoid treatment., Main Outcomes and Measures: Main outcomes were patient characteristics associated with postdischarge glucocorticoid treatment, laboratory test result trajectories, and adverse events. Multivariable regression was used to evaluate factors associated with postdischarge weight gain (≥2 kg in 3 months) and hyperglycemia during illness., Results: Among 186 patients, the median age was 10.4 years (IQR, 6.7-14.2 years); most were male (107 [57.5%]), Black non-Hispanic (60 [32.3%]), and Hispanic or Latino (59 [31.7%]). Most children were critically ill (intensive care unit admission, 163 [87.6%]; vasopressor receipt, 134 [72.0%]) and received inpatient glucocorticoid treatment (178 [95.7%]). Most were discharged with continued glucocorticoid treatment (173 [93.0%]); median discharge dose was 42 mg/d (IQR, 30-60 mg/d) or 1.1 mg/kg/d (IQR, 0.7-1.7 mg/kg/d). Inpatient severity of illness was not associated with duration of postdischarge glucocorticoid treatment. Outpatient treatment duration varied (median, 23 days; IQR, 15-32 days). Time to normalization of C-reactive protein and ferritin levels was similar for glucocorticoid duration of less than 3 weeks vs 3 or more weeks. Readmission occurred in 7 patients (3.8%); none was for cardiovascular dysfunction. Hyperglycemia developed in 14 patients (8.1%). Seventy-five patients (43%) gained 2 kg or more after discharge (median 4.1 kg; IQR, 3.0-6.0 kg). Inpatient high-dose intravenous and oral glucocorticoid therapy was associated with postdischarge weight gain (adjusted odds ratio, 6.91; 95% CI, 1.92-24.91)., Conclusions and Relevance: In this multicenter cohort of patients with MIS-C and cardiovascular dysfunction, postdischarge glucocorticoid treatment was often prolonged, but clinical outcomes were similar in patients prescribed shorter courses. Outpatient weight gain was common. Readmission was infrequent, with none for cardiovascular dysfunction. These findings suggest that strategies are needed to optimize postdischarge glucocorticoid courses for patients with MIS-C. more...
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- 2022
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26. Association of Race and Ethnicity With Medication Use for Pediatric Lupus in the Childhood Arthritis and Rheumatology Research Alliance Registry.
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Roberts JE, Berbert L, Chang J, and Son MBF
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Objective: Black and Hispanic children with pediatric lupus (pSLE) have higher morbidity and mortality than non-Hispanic White children. The extent to which differences in outcomes are due to treatment disparities, including medication use, is unknown. We aimed to determine whether medication use in pSLE is associated with race and ethnicity in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry., Methods: Patients with pSLE enrolled in the CARRA Registry from 2017 to 2020 were included. Multivariable mixed-effect logistic regression, adjusted for site of care, was used to compare use of antimalarials, high-dose oral glucocorticoids, and rituximab in Black and Hispanic children., Results: We identified 639 children with pSLE, of whom 480 had at least 1 year of follow-up. At enrollment, 89% of patients were prescribed an antimalarial and 50% were on high-dose glucocorticoids. Of those with 1 year of follow-up, 12% received rituximab. Nephritis, shorter disease duration, and higher Systemic Lupus Erythematosus Disease Activity Index 2000 scores were associated with high-dose glucocorticoid use. Antimalarial use was higher among those with nephritis and lower in children with no insurance. Rituximab use was associated with Black race in the fixed-effects model but not when adjusted for site of care., Conclusion: We identified differences in medication use by race and insurance status. Site of care was associated with the racial differences observed in rituximab use. Further research is needed to optimize pSLE treatments particularly where use is highly variable, including glucocorticoid dosing and use of rituximab, and understand the impact of practice variation on disparities in pSLE outcomes., (© 2022 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.) more...
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- 2022
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27. Longitudinal assessment of preparation for care transition among adolescents and young adults with rheumatologic disease: a single-center pilot study.
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Roberts JE, Halyabar O, Petty CR, Alfieri M, Esty B, Dallas J, Hazen M, Stein S, and Son MBF
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- Young Adult, Adolescent, Humans, Child, Patient Transfer, Pilot Projects, Transition to Adult Care, Rheumatology, Arthritis, Rheumatoid
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Adolescents and young adults (AYA) with rheumatologic diseases are at high risk for poor outcomes and gaps in care when transitioning from pediatric to adult care. However, tools for evaluating transition readiness and assessing the impact of transition interventions are limited. We implemented a written transition policy at our pediatric rheumatology center and evaluated preparation for transition among AYA 16 and older before and after distribution. 31 of 77 patients completed the follow-up survey (response rate 40%). Patient report of transition counseling increased following written transition policy implementation, though these results were not statistically significant in our small cohort. Most follow-up respondents (n = 19, 61%) had not yet completed care transfer; 4 (13%) had arranged a visit with an adult rheumatologist and 8 (26%) had fully transitioned to adult care. Those who successfully completed care transfer were older, had completed higher levels of education, and had significantly higher baseline transition preparation scores compared to those with no transfer arranged or planned visit only. Our single-center pilot study demonstrated that longitudinal assessment of transition preparation is feasible and that scores are significantly associated with care transfer outcomes. Tracking transition preparation over time may provide practices with information on areas of highest need for transition guidance and predict successful transfer among AYA with rheumatologic disease., (© 2022. The Author(s).) more...
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- 2022
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28. SARS-CoV-2-specific T cell responses in patients with multisystem inflammatory syndrome in children.
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Lam KP, Chiñas M, Julé AM, Taylor M, Ohashi M, Benamar M, Crestani E, Son MBF, Chou J, Gebhart C, Chatila T, Newburger J, Randolph A, Gutierrez-Arcelus M, and Henderson LA
- Subjects
- Child, Humans, SARS-CoV-2, Systemic Inflammatory Response Syndrome, T-Lymphocytes, COVID-19 complications, Connective Tissue Diseases
- Abstract
Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infections that occurs in the pediatric population. We sought to characterize T cell responses in MIS-C compared to COVID-19 and pediatric hyperinflammatory syndromes. MIS-C was distinct from COVID-19 and hyperinflammatory syndromes due to an expansion of T cells expressing TRBV11-2 that was not associated with HLA genotype. Children diagnosed with MIS-C, but who were negative for SARS-CoV-2 by PCR and serology, did not display Vβ skewing. There was no difference in the proportion of T cells that became activated after stimulation with SARS-CoV-2 peptides in children with MIS-C compared to convalescent COVID-19. The frequency of SARS-CoV-2-specific TCRs and the antigens recognized by these TCRs were comparable in MIS-C and COVID-19. Expansion of Vβ11-2
+ T cells was a specific biomarker of MIS-C patients with laboratory confirmed SARS-CoV-2 infections. Children with MIS-C had robust antigen-specific T cell responses to SARS-CoV-2., Competing Interests: Declaration of Competing Interest LAH has received salary support from CARRA; consulting fees from Sobi, Pfizer, and Adaptive Biotechnologies; and investigator-initiated research grants from Bristol-Myers Squibb., (Copyright © 2022 Elsevier Inc. All rights reserved.) more...- Published
- 2022
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29. Treatment of Multisystem Inflammatory Syndrome in Children: Understanding Differences in Results of Comparative Effectiveness Studies.
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Melgar M, Seaby EG, McArdle AJ, Young CC, Campbell AP, Murray NL, Patel MM, Levin M, Randolph AG, and Son MBF
- Abstract
Objective: Two cohort studies in patients with multisystem inflammatory syndrome in children (MIS-C) demonstrated contrasting results regarding the benefit of initial immunomodulatory treatment with intravenous immunoglobulin (IVIG) alone versus IVIG and glucocorticoids. We sought to determine whether application of different MIS-C definitions and differing disease severity between cohorts underlay discrepant results., Methods: The Overcoming COVID-19 Public Health Surveillance Registry (OC-19) included patients meeting the US Centers for Disease Control and Prevention (CDC) MIS-C definition, whereas the Best Available Treatment Study (BATS) applied the World Health Organization (WHO) definition. We applied the WHO definition to the OC-19 cohort and the CDC definition to the BATS cohort and determined the proportion that did not meet the alternate definition. We compared illness severity indicators between cohorts., Results: Of 349 OC-19 patients, 9.5% did not meet the WHO definition. Of 350 BATS patients, 10.3% did not meet the CDC definition. Most organ system involvement was similar between the cohorts, but more OC-19 patients had WHO-defined cardiac involvement (87.1% vs 79.4%, P = 0.008). OC-19 patients were more often admitted to intensive care (61.0% vs 44.8%, P < 0.001) and more often received vasopressors or inotropes (39.5% vs 22.9%, P < 0.001) before immunomodulatory treatment., Conclusion: Greater illness severity and cardiovascular involvement in the OC-19 cohort compared with the BATS cohort, and not use of different MIS-C case definitions, may have contributed to differing study conclusions about optimal initial treatment for MIS-C. Disease severity should be considered in future MIS-C study designs and treatment recommendations to identify patients who would benefit from aggressive immunomodulatory treatment., (© 2022 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.) more...
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- 2022
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30. An Evidence-Based Guideline Improves Outcomes for Patients With Hemophagocytic Lymphohistiocytosis and Macrophage Activation Syndrome.
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Taylor ML, Hoyt KJ, Han J, Benson L, Case S, Chandler MT, Chang MH, Platt C, Cohen EM, Day-Lewis M, Dedeoglu F, Gorman M, Hausmann JS, Janssen E, Lee PY, Lo J, Priebe GP, Lo MS, Meidan E, Nigrovic PA, Roberts JE, Son MBF, Sundel RP, Alfieri M, Yeun JC, Shobiye DM, Degar B, Chang JC, Halyabar O, Hazen MM, and Henderson LA more...
- Subjects
- Humans, Child, Retrospective Studies, C-Reactive Protein, Biomarkers, Macrophage Activation Syndrome drug therapy, Macrophage Activation Syndrome diagnosis, Lymphohistiocytosis, Hemophagocytic therapy
- Abstract
Objective: To compare clinical outcomes in children with hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) who were managed before and after implementation of an evidence-based guideline (EBG)., Methods: A management algorithm for MAS-HLH was developed at our institution based on literature review, expert opinion, and consensus building across multiple pediatric subspecialties. An electronic medical record search retrospectively identified hospitalized patients with MAS-HLH in the pre-EBG (October 15, 2015, to December 4, 2017) and post-EBG (January 1, 2018, to January 21, 2020) time periods. Predetermined outcome metrics were evaluated in the 2 cohorts., Results: After the EBG launch, 57 children were identified by house staff as potential patients with MAS-HLH, and rheumatology was consulted for management. Ultimately, 17 patients were diagnosed with MAS-HLH by the treating team. Of these, 59% met HLH 2004 criteria, and 94% met 2016 classification criteria for MAS complicating systemic juvenile idiopathic arthritis. There was a statistically significant reduction in mortality from 50% before implementation of the EBG to 6% in the post-EBG cohort ( P = 0.02). There was a significant improvement in time to 50% reduction in C-reactive protein level in the post-EBG vs pre-EBG cohorts (log-rank P < 0.01). There were trends toward faster time to MAS-HLH diagnosis, faster initiation of immunosuppressive therapy, shorter length of hospital stay, and more rapid normalization of MAS-HLH-related biomarkers in the patients post-EBG., Conclusion: While the observed improvements may be partially attributed to advances in treatment of MAS-HLH that have accumulated over time, this analysis also suggests that a multidisciplinary treatment pathway for MAS-HLH contributed meaningfully to favorable patient outcomes., (Copyright © 2022 by the Journal of Rheumatology.) more...
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- 2022
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31. Racial Disparities in Renal Outcomes Over Time Among Hospitalized Children With Systemic Lupus Erythematosus.
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Chang JC, Sears C, Torres V, and Son MBF
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- Adult, Child, Child, Hospitalized, Ethnicity, Humans, Minority Groups, Young Adult, Kidney Failure, Chronic therapy, Lupus Erythematosus, Systemic diagnosis
- Abstract
Objective: Racial and ethnic minority groups have excess morbidity related to renal disease in pediatric-onset systemic lupus erythematosus (SLE). This study was undertaken to evaluate temporal trends in renal outcomes and racial disparities among hospitalized children with SLE over a period of 14 years., Methods: We identified patients 21 years old or younger with discharge diagnoses of SLE in the Pediatric Health Information System inpatient database (2006-2019). Adverse renal outcomes included end-stage renal disease (ESRD), dialysis, or transplant, analyzed as a composite and separately. We estimated the odds of adverse renal outcomes at any hospitalization or the first occurrence of an adverse renal outcome, adjusted for calendar period, patient characteristics, and clustering by hospital. We tested whether racial disparities differed by calendar period., Results: There were 20,893 admissions for 7,434 SLE patients, of which 32%, 16%, 12%, and 8% were Black, Hispanic White, Hispanic Other, and Asian, respectively. Proportions of admissions with adverse renal outcomes decreased over time (P < 0.01). Black children remained at the highest risk of adverse renal outcomes at any admission (odds ratio [OR] 2.5 [95% confidence interval (95% CI) 1.8-3.5] versus non-Hispanic White patients). Black and Asian children remained at a higher risk of incident adverse renal outcomes, driven by ESRD among Black children (OR 1.6 [95% CI 1.2-2.1]) and dialysis among Asians (OR 1.7 [95% CI 1.1-2.7]). Relative disparities did not change significantly over time., Conclusion: Significant reductions in ESRD and dialysis occurred over time for children with SLE across all racial and ethnic groups. The lack of corresponding reductions in racial disparities highlights the need for targeted interventions to achieve greater treatment benefit among higher risk groups., (© 2022 American College of Rheumatology.) more...
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- 2022
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32. When vaccine adverse event reporting generates hope, not fear.
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Chang JC and Son MBF
- Subjects
- Humans, Vaccines adverse effects
- Abstract
Competing Interests: JCC has received grant funding from GlaxoSmithKine for investigator-driven research unrelated to this work. MBFS declares no competing interests.
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- 2022
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33. Insurance Delays in Initiation of Tumor Necrosis Factor Inhibitors in Children With Juvenile Idiopathic Arthritis.
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Roberts JE, Fan M, and Son MBF
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- Child, Humans, Tumor Necrosis Factor Inhibitors therapeutic use, Tumor Necrosis Factor-alpha, Antirheumatic Agents therapeutic use, Arthritis, Juvenile drug therapy, Arthritis, Juvenile pathology, Insurance
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- 2022
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34. American College of Rheumatology Clinical Guidance for Multisystem Inflammatory Syndrome in Children Associated With SARS-CoV-2 and Hyperinflammation in Pediatric COVID-19: Version 3.
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Henderson LA, Canna SW, Friedman KG, Gorelik M, Lapidus SK, Bassiri H, Behrens EM, Kernan KF, Schulert GS, Seo P, Son MBF, Tremoulet AH, VanderPluym C, Yeung RSM, Mudano AS, Turner AS, Karp DR, and Mehta JJ more...
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- Adult, Child, Humans, SARS-CoV-2, Systemic Inflammatory Response Syndrome therapy, United States, COVID-19 complications, Rheumatology
- Abstract
Objective: To provide guidance on the management of Multisystem Inflammatory Syndrome in Children (MIS-C), a condition characterized by fever, inflammation, and multiorgan dysfunction that manifests late in the course of SARS-CoV-2 infection. Recommendations are also provided for children with hyperinflammation during COVID-19, the acute, infectious phase of SARS-CoV-2 infection., Methods: The Task Force is composed of 9 pediatric rheumatologists and 2 adult rheumatologists, 2 pediatric cardiologists, 2 pediatric infectious disease specialists, and 1 pediatric critical care physician. Preliminary statements addressing clinical questions related to MIS-C and hyperinflammation in COVID-19 were developed based on evidence reports. Consensus was built through a modified Delphi process that involved anonymous voting and webinar discussion. A 9-point scale was used to determine the appropriateness of each statement (median scores of 1-3 for inappropriate, 4-6 for uncertain, and 7-9 for appropriate). Consensus was rated as low, moderate, or high based on dispersion of the votes. Approved guidance statements were those that were classified as appropriate with moderate or high levels of consensus, which were prespecified before voting., Results: The guidance was approved in June 2020 and updated in November 2020 and October 2021, and consists of 41 final guidance statements accompanied by flow diagrams depicting the diagnostic pathway for MIS-C and recommendations for initial immunomodulatory treatment of MIS-C., Conclusion: Our understanding of SARS-CoV-2-related syndromes in the pediatric population continues to evolve. This guidance document reflects currently available evidence coupled with expert opinion, and will be revised as further evidence becomes available., (© 2022 American College of Rheumatology.) more...
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- 2022
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35. An integrated framework for identifying clinical-laboratory indicators for novel pandemics: COVID-19 and MIS-C.
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Nahari AD, Son MBF, Newburger JW, and Reis BY
- Abstract
During the critical early stages of an emerging pandemic, limited availability of pathogen-specific testing can severely inhibit individualized risk screening and pandemic tracking. Standard clinical laboratory tests offer a widely available complementary data source for first-line risk screening and pandemic surveillance. Here, we propose an integrated framework for developing clinical-laboratory indicators for novel pandemics that combines population-level and individual-level analyses. We apply this framework to 7,520,834 clinical laboratory tests recorded over five years and find clinical-lab-test combinations that are strongly associated with SARS-CoV-2 PCR test results and Multisystem Inflammatory Syndrome in Children (MIS-C) diagnoses: Interleukin-related tests (e.g. IL4, IL10) were most strongly associated with SARS-CoV-2 infection and MIS-C, while other more widely available tests (ferritin, D-dimer, fibrinogen, alanine transaminase, and C-reactive protein) also had strong associations. When novel pandemics emerge, this framework can be used to identify specific combinations of clinical laboratory tests for public health tracking and first-line individualized risk screening., (© 2022. The Author(s).) more...
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- 2022
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36. An Update on Multisystem Inflammatory Syndrome in Children Related to SARS-CoV-2.
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Dionne A, Son MBF, and Randolph AG
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- Adolescent, COVID-19 diagnosis, COVID-19 epidemiology, COVID-19 pathology, COVID-19 therapy, Child, Child, Preschool, History, 21st Century, Humans, Infant, Systemic Inflammatory Response Syndrome epidemiology, COVID-19 complications, Systemic Inflammatory Response Syndrome diagnosis, Systemic Inflammatory Response Syndrome pathology, Systemic Inflammatory Response Syndrome therapy
- Abstract
Competing Interests: The authors have no funding or conflicts of interest to disclose.
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- 2022
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37. Data-driven clustering identifies features distinguishing multisystem inflammatory syndrome from acute COVID-19 in children and adolescents.
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Geva A, Patel MM, Newhams MM, Young CC, Son MBF, Kong M, Maddux AB, Hall MW, Riggs BJ, Singh AR, Giuliano JS, Hobbs CV, Loftis LL, McLaughlin GE, Schwartz SP, Schuster JE, Babbitt CJ, Halasa NB, Gertz SJ, Doymaz S, Hume JR, Bradford TT, Irby K, Carroll CL, McGuire JK, Tarquinio KM, Rowan CM, Mack EH, Cvijanovich NZ, Fitzgerald JC, Spinella PC, Staat MA, Clouser KN, Soma VL, Dapul H, Maamari M, Bowens C, Havlin KM, Mourani PM, Heidemann SM, Horwitz SM, Feldstein LR, Tenforde MW, Newburger JW, Mandl KD, and Randolph AG more...
- Abstract
Background: Multisystem inflammatory syndrome in children (MIS-C) consensus criteria were designed for maximal sensitivity and therefore capture patients with acute COVID-19 pneumonia., Methods: We performed unsupervised clustering on data from 1,526 patients (684 labeled MIS-C by clinicians) <21 years old hospitalized with COVID-19-related illness admitted between 15 March 2020 and 31 December 2020. We compared prevalence of assigned MIS-C labels and clinical features among clusters, followed by recursive feature elimination to identify characteristics of potentially misclassified MIS-C-labeled patients., Findings: Of 94 clinical features tested, 46 were retained for clustering. Cluster 1 patients ( N = 498; 92% labeled MIS-C) were mostly previously healthy (71%), with mean age 7·2 ± 0·4 years, predominant cardiovascular (77%) and/or mucocutaneous (82%) involvement, high inflammatory biomarkers, and mostly SARS-CoV-2 PCR negative (60%). Cluster 2 patients ( N = 445; 27% labeled MIS-C) frequently had pre-existing conditions (79%, with 39% respiratory), were similarly 7·4 ± 2·1 years old, and commonly had chest radiograph infiltrates (79%) and positive PCR testing (90%). Cluster 3 patients ( N = 583; 19% labeled MIS-C) were younger (2·8 ± 2·0 y), PCR positive (86%), with less inflammation. Radiographic findings of pulmonary infiltrates and positive SARS-CoV-2 PCR accurately distinguished cluster 2 MIS-C labeled patients from cluster 1 patients., Interpretation: Using a data driven, unsupervised approach, we identified features that cluster patients into a group with high likelihood of having MIS-C. Other features identified a cluster of patients more likely to have acute severe COVID-19 pulmonary disease, and patients in this cluster labeled by clinicians as MIS-C may be misclassified. These data driven phenotypes may help refine the diagnosis of MIS-C., Competing Interests: All authors report receiving funding from the Centers for Disease Control and Prevention for the current study. AG reports receiving grants from the NIH outside of the submitted work. ABM reports receiving grants from the Francis Family Foundation and from the NIH/NICHD (K23HD096018) outside of the submitted work. CVH reports receiving consulting fees from DYNAMED and BIOFIRE outside of the submitted work. JES reports receiving grants from Merck outside of the submitted work. NBH reports receiving grants from Sanofi, Quidel, the NIH, and the CDC; consulting fees from Moderna; and an educational grant from Genetech outside of the submitted work. CMR reports receiving grants from the NIH/NHLBI (K23HL150244) outside of the submitted work. NZC reports receiving grants or contracts from Boston Children's Hospital and Cincinnati Children's Hospital and Medical Center outside of the submitted work. JCF reports receiving grants from the NIH outside of the submitted work. HD reports payments from Delex Pharma International Inc. outside of the submitted work. PMM reports receiving grants from the NIH and serving as a member of data safety monitoring board for the NIH supported KIDS-DOT trial outside of the submitted work. AGR reports receiving royalties from UpToDate outside of the submitted work. All other authors have nothing to declare., (© 2021 The Authors.) more...
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- 2021
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38. Therapy for Multisystem Inflammatory Syndrome in Children. Reply.
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Son MBF, Newburger JW, and Randolph AG
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- Child, Humans, Syndrome, Systemic Inflammatory Response Syndrome, COVID-19 complications
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- 2021
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39. Th1 polarization defines the synovial fluid T cell compartment in oligoarticular juvenile idiopathic arthritis.
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Julé AM, Hoyt KJ, Wei K, Gutierrez-Arcelus M, Taylor ML, Ng J, Lederer JA, Case SM, Chang MH, Cohen EM, Dedeoglu F, Hazen MM, Hausmann JS, Halyabar O, Janssen E, Lo J, Lo MS, Meidan E, Roberts JE, Son MBF, Sundel RP, Lee PY, Chatila T, Nigrovic PA, and Henderson LA more...
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- Adolescent, Arthritis, Juvenile genetics, CD4-Positive T-Lymphocytes physiology, CD8-Positive T-Lymphocytes physiology, Case-Control Studies, Child, Child, Preschool, DNA Methylation, Female, Humans, Immunophenotyping, Infant, Intraepithelial Lymphocytes physiology, Male, Sequence Analysis, RNA, Single-Cell Analysis, T-Lymphocytes, Regulatory physiology, Th1 Cells physiology, Transcriptome, Arthritis, Juvenile immunology, Cell Polarity, Synovial Fluid immunology, T-Lymphocytes physiology
- Abstract
Oligoarticular juvenile idiopathic arthritis (oligo JIA) is the most common form of chronic inflammatory arthritis in children, yet the cause of this disease remains unknown. To understand immune responses in oligo JIA, we immunophenotyped synovial fluid T cells with flow cytometry, bulk RNA-Seq, single-cell RNA-Seq (scRNA-Seq), DNA methylation studies, and Treg suppression assays. In synovial fluid, CD4+, CD8+, and γδ T cells expressed Th1-related markers, whereas Th17 cells were not enriched. Th1 skewing was prominent in CD4+ T cells, including Tregs, and was associated with severe disease. Transcriptomic studies confirmed a Th1 signature in CD4+ T cells from synovial fluid. The regulatory gene expression signature was preserved in Tregs, even those exhibiting Th1 polarization. These Th1-like Tregs maintained Treg-specific methylation patterns and suppressive function, supporting the stability of this Treg population in the joint. Although synovial fluid CD4+ T cells displayed an overall Th1 phenotype, scRNA-Seq uncovered heterogeneous effector and regulatory subpopulations, including IFN-induced Tregs, peripheral helper T cells, and cytotoxic CD4+ T cells. In conclusion, oligo JIA is characterized by Th1 polarization that encompasses Tregs but does not compromise their regulatory identity. Targeting Th1-driven inflammation and augmenting Treg function may represent important therapeutic approaches in oligo JIA. more...
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- 2021
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40. Multisystem Inflammatory Syndrome in Children - Initial Therapy and Outcomes.
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Son MBF, Murray N, Friedman K, Young CC, Newhams MM, Feldstein LR, Loftis LL, Tarquinio KM, Singh AR, Heidemann SM, Soma VL, Riggs BJ, Fitzgerald JC, Kong M, Doymaz S, Giuliano JS Jr, Keenaghan MA, Hume JR, Hobbs CV, Schuster JE, Clouser KN, Hall MW, Smith LS, Horwitz SM, Schwartz SP, Irby K, Bradford TT, Maddux AB, Babbitt CJ, Rowan CM, McLaughlin GE, Yager PH, Maamari M, Mack EH, Carroll CL, Montgomery VL, Halasa NB, Cvijanovich NZ, Coates BM, Rose CE, Newburger JW, Patel MM, and Randolph AG more...
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- Adolescent, COVID-19 complications, COVID-19 immunology, COVID-19 mortality, Child, Child, Preschool, Cohort Studies, Combined Modality Therapy, Drug Therapy, Combination, Female, Hospitalization, Humans, Immunomodulation, Infant, Logistic Models, Male, Propensity Score, Public Health Surveillance, Shock etiology, Shock prevention & control, Systemic Inflammatory Response Syndrome complications, Systemic Inflammatory Response Syndrome immunology, Systemic Inflammatory Response Syndrome mortality, Treatment Outcome, Ventricular Dysfunction, Left etiology, Young Adult, Glucocorticoids therapeutic use, Immunoglobulins, Intravenous therapeutic use, Systemic Inflammatory Response Syndrome drug therapy, Ventricular Dysfunction, Left prevention & control, COVID-19 Drug Treatment
- Abstract
Background: The assessment of real-world effectiveness of immunomodulatory medications for multisystem inflammatory syndrome in children (MIS-C) may guide therapy., Methods: We analyzed surveillance data on inpatients younger than 21 years of age who had MIS-C and were admitted to 1 of 58 U.S. hospitals between March 15 and October 31, 2020. The effectiveness of initial immunomodulatory therapy (day 0, indicating the first day any such therapy for MIS-C was given) with intravenous immune globulin (IVIG) plus glucocorticoids, as compared with IVIG alone, was evaluated with propensity-score matching and inverse probability weighting, with adjustment for baseline MIS-C severity and demographic characteristics. The primary outcome was cardiovascular dysfunction (a composite of left ventricular dysfunction or shock resulting in the use of vasopressors) on or after day 2. Secondary outcomes included the components of the primary outcome, the receipt of adjunctive treatment (glucocorticoids in patients not already receiving glucocorticoids on day 0, a biologic, or a second dose of IVIG) on or after day 1, and persistent or recurrent fever on or after day 2., Results: A total of 518 patients with MIS-C (median age, 8.7 years) received at least one immunomodulatory therapy; 75% had been previously healthy, and 9 died. In the propensity-score-matched analysis, initial treatment with IVIG plus glucocorticoids (103 patients) was associated with a lower risk of cardiovascular dysfunction on or after day 2 than IVIG alone (103 patients) (17% vs. 31%; risk ratio, 0.56; 95% confidence interval [CI], 0.34 to 0.94). The risks of the components of the composite outcome were also lower among those who received IVIG plus glucocorticoids: left ventricular dysfunction occurred in 8% and 17% of the patients, respectively (risk ratio, 0.46; 95% CI, 0.19 to 1.15), and shock resulting in vasopressor use in 13% and 24% (risk ratio, 0.54; 95% CI, 0.29 to 1.00). The use of adjunctive therapy was lower among patients who received IVIG plus glucocorticoids than among those who received IVIG alone (34% vs. 70%; risk ratio, 0.49; 95% CI, 0.36 to 0.65), but the risk of fever was unaffected (31% and 40%, respectively; risk ratio, 0.78; 95% CI, 0.53 to 1.13). The inverse-probability-weighted analysis confirmed the results of the propensity-score-matched analysis., Conclusions: Among children and adolescents with MIS-C, initial treatment with IVIG plus glucocorticoids was associated with a lower risk of new or persistent cardiovascular dysfunction than IVIG alone. (Funded by the Centers for Disease Control and Prevention.)., (Copyright © 2021 Massachusetts Medical Society.) more...
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- 2021
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41. Reply.
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Henderson LA, Friedman KG, Son MBF, Kernan KF, Canna SW, Gorelik M, Lapidus SK, Ferris A, Schulert GS, Seo P, Tremoulet AH, Yeung RSM, Karp DR, Bassiri H, Behrens EM, and Mehta JJ
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- 2021
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42. Multiple Emergency Department Visits for a Diagnosis of Kawasaki Disease: An Examination of Risk Factors and Outcomes.
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Lo J, Gauvreau K, Baker AL, de Ferranti SD, Friedman KG, Lo MS, Dedeoglu F, Sundel RP, Newburger JW, and Son MBF
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- Adolescent, Boston epidemiology, Child, Child, Preschool, Female, Humans, Infant, Logistic Models, Male, Mucocutaneous Lymph Node Syndrome ethnology, Mucocutaneous Lymph Node Syndrome therapy, Prognosis, Retrospective Studies, Delayed Diagnosis statistics & numerical data, Emergency Service, Hospital, Mucocutaneous Lymph Node Syndrome diagnosis
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Objectives: To determine predictors of >1 emergency department (ED) visit for a Kawasaki disease diagnosis in a quaternary care pediatric hospital and compare outcomes between patients with 1 vs >1 visit for Kawasaki disease diagnosis., Study Design: Medical records of patients evaluated for Kawasaki disease between January 2006 and August 2018 at Boston Children's Hospital were abstracted for demographic and clinical data. Predictors of >1 visit were explored using logistic regression and classification and regression tree analysis., Results: Of 530 patients diagnosed with Kawasaki disease, 117 (22%) required multiple ED visits for Kawasaki disease diagnosis. Multivariable regression and classification and regression tree analysis identified ≤2 Kawasaki disease criteria (OR 33.9; 95% CI 18.1-63.6), <3 days of fever at the first visit (OR 3.47; 95% CI 1.77-6.84), and non-White race (OR 2.15; 95% CI 1.18-3.95) as predictors of >1 visit. There were no significant differences in duration of hospitalization, day of illness at initial Kawasaki disease treatment, intravenous immunoglobulin resistance, need for adjunctive therapies, or coronary artery outcomes between patients diagnosed with Kawasaki disease at initial visit vs subsequent visits., Conclusions: Incomplete Kawasaki disease criteria, fewer days of fever, and non-White race were significant predictors of multiple ED visits for Kawasaki disease diagnosis in this single institution study. Our findings underscore the importance of maintaining a high index of suspicion for Kawasaki disease in patients with <4 Kawasaki disease criteria. Further research is needed to determine causes for increased healthcare use in non-White patients to receive a Kawasaki disease diagnosis., (Copyright © 2021 Elsevier Inc. All rights reserved.) more...
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- 2021
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43. Neurologic Involvement in Children and Adolescents Hospitalized in the United States for COVID-19 or Multisystem Inflammatory Syndrome.
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LaRovere KL, Riggs BJ, Poussaint TY, Young CC, Newhams MM, Maamari M, Walker TC, Singh AR, Dapul H, Hobbs CV, McLaughlin GE, Son MBF, Maddux AB, Clouser KN, Rowan CM, McGuire JK, Fitzgerald JC, Gertz SJ, Shein SL, Munoz AC, Thomas NJ, Irby K, Levy ER, Staat MA, Tenforde MW, Feldstein LR, Halasa NB, Giuliano JS Jr, Hall MW, Kong M, Carroll CL, Schuster JE, Doymaz S, Loftis LL, Tarquinio KM, Babbitt CJ, Nofziger RA, Kleinman LC, Keenaghan MA, Cvijanovich NZ, Spinella PC, Hume JR, Wellnitz K, Mack EH, Michelson KN, Flori HR, Patel MM, and Randolph AG more...
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- Adolescent, COVID-19 etiology, COVID-19 mortality, Child, Child, Preschool, Critical Care, Female, Hospitalization, Humans, Male, Nervous System Diseases mortality, Patient Discharge statistics & numerical data, Respiratory Distress Syndrome etiology, Respiratory Distress Syndrome therapy, Systemic Inflammatory Response Syndrome complications, Treatment Outcome, United States epidemiology, COVID-19 complications, Nervous System Diseases etiology, Systemic Inflammatory Response Syndrome etiology
- Abstract
Importance: Coronavirus disease 2019 (COVID-19) affects the nervous system in adult patients. The spectrum of neurologic involvement in children and adolescents is unclear., Objective: To understand the range and severity of neurologic involvement among children and adolescents associated with COVID-19., Setting, Design, and Participants: Case series of patients (age <21 years) hospitalized between March 15, 2020, and December 15, 2020, with positive severe acute respiratory syndrome coronavirus 2 test result (reverse transcriptase-polymerase chain reaction and/or antibody) at 61 US hospitals in the Overcoming COVID-19 public health registry, including 616 (36%) meeting criteria for multisystem inflammatory syndrome in children. Patients with neurologic involvement had acute neurologic signs, symptoms, or diseases on presentation or during hospitalization. Life-threatening involvement was adjudicated by experts based on clinical and/or neuroradiologic features., Exposures: Severe acute respiratory syndrome coronavirus 2., Main Outcomes and Measures: Type and severity of neurologic involvement, laboratory and imaging data, and outcomes (death or survival with new neurologic deficits) at hospital discharge., Results: Of 1695 patients (909 [54%] male; median [interquartile range] age, 9.1 [2.4-15.3] years), 365 (22%) from 52 sites had documented neurologic involvement. Patients with neurologic involvement were more likely to have underlying neurologic disorders (81 of 365 [22%]) compared with those without (113 of 1330 [8%]), but a similar number were previously healthy (195 [53%] vs 723 [54%]) and met criteria for multisystem inflammatory syndrome in children (126 [35%] vs 490 [37%]). Among those with neurologic involvement, 322 (88%) had transient symptoms and survived, and 43 (12%) developed life-threatening conditions clinically adjudicated to be associated with COVID-19, including severe encephalopathy (n = 15; 5 with splenial lesions), stroke (n = 12), central nervous system infection/demyelination (n = 8), Guillain-Barré syndrome/variants (n = 4), and acute fulminant cerebral edema (n = 4). Compared with those without life-threatening conditions (n = 322), those with life-threatening neurologic conditions had higher neutrophil-to-lymphocyte ratios (median, 12.2 vs 4.4) and higher reported frequency of D-dimer greater than 3 μg/mL fibrinogen equivalent units (21 [49%] vs 72 [22%]). Of 43 patients who developed COVID-19-related life-threatening neurologic involvement, 17 survivors (40%) had new neurologic deficits at hospital discharge, and 11 patients (26%) died., Conclusions and Relevance: In this study, many children and adolescents hospitalized for COVID-19 or multisystem inflammatory syndrome in children had neurologic involvement, mostly transient symptoms. A range of life-threatening and fatal neurologic conditions associated with COVID-19 infrequently occurred. Effects on long-term neurodevelopmental outcomes are unknown. more...
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- 2021
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44. Mistaken MIS-C: A Case Series of Bacterial Enteritis Mimicking MIS-C.
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Dworsky ZD, Roberts JE, Son MBF, Tremoulet AH, Newburger JW, and Burns JC
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- Bacterial Infections microbiology, Biomarkers, Child, Child, Preschool, Diagnosis, Differential, Diagnostic Errors, Enteritis microbiology, Female, Hospitalization, Humans, Male, Symptom Assessment, Bacterial Infections diagnosis, Enteritis diagnosis, Systemic Inflammatory Response Syndrome diagnosis
- Abstract
Multisystem inflammatory syndrome in children following severe acute respiratory syndrome coronavirus 2 infection is characterized by fever, elevated inflammatory markers, and multisystem organ involvement. Presentations are variable but often include gastrointestinal symptoms. We describe 5 children with fever and gastrointestinal symptoms initially concerning for multisystem inflammatory syndrome in children who were ultimately diagnosed with bacterial enteritis, highlighting the diagnostic challenges presented by the severe acute respiratory syndrome coronavirus 2 pandemic., Competing Interests: There are no conflicts of interest for any authors., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.) more...
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- 2021
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45. American College of Rheumatology Clinical Guidance for Multisystem Inflammatory Syndrome in Children Associated With SARS-CoV-2 and Hyperinflammation in Pediatric COVID-19: Version 2.
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Henderson LA, Canna SW, Friedman KG, Gorelik M, Lapidus SK, Bassiri H, Behrens EM, Ferris A, Kernan KF, Schulert GS, Seo P, Son MBF, Tremoulet AH, Yeung RSM, Mudano AS, Turner AS, Karp DR, and Mehta JJ more...
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- Adolescent, Advisory Committees, Anticoagulants therapeutic use, Antirheumatic Agents therapeutic use, Child, Child, Preschool, Delphi Technique, Diagnosis, Differential, Glucocorticoids therapeutic use, Humans, Immunoglobulins, Intravenous therapeutic use, Immunologic Factors therapeutic use, Infant, Infant, Newborn, Inflammation, Interleukin 1 Receptor Antagonist Protein therapeutic use, Mucocutaneous Lymph Node Syndrome diagnosis, Platelet Aggregation Inhibitors therapeutic use, Rheumatology, SARS-CoV-2, Young Adult, COVID-19 diagnosis, COVID-19 therapy, Systemic Inflammatory Response Syndrome diagnosis, Systemic Inflammatory Response Syndrome therapy
- Abstract
Objective: To provide guidance on the management of Multisystem Inflammatory Syndrome in Children (MIS-C), a condition characterized by fever, inflammation, and multiorgan dysfunction that manifests late in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Recommendations are also provided for children with hyperinflammation during coronavirus disease 2019 (COVID-19), the acute, infectious phase of SARS-CoV-2 infection., Methods: The Task Force was composed of 9 pediatric rheumatologists and 2 adult rheumatologists, 2 pediatric cardiologists, 2 pediatric infectious disease specialists, and 1 pediatric critical care physician. Preliminary statements addressing clinical questions related to MIS-C and hyperinflammation in COVID-19 were developed based on evidence reports. Consensus was built through a modified Delphi process that involved anonymous voting and webinar discussion. A 9-point scale was used to determine the appropriateness of each statement (median scores of 1-3 for inappropriate, 4-6 for uncertain, and 7-9 for appropriate). Consensus was rated as low, moderate, or high based on dispersion of the votes. Approved guidance statements were those that were classified as appropriate with moderate or high levels of consensus, which were prespecified before voting., Results: The first version of the guidance was approved in June 2020, and consisted of 40 final guidance statements accompanied by a flow diagram depicting the diagnostic pathway for MIS-C. The document was revised in November 2020, and a new flow diagram with recommendations for initial immunomodulatory treatment of MIS-C was added., Conclusion: Our understanding of SARS-CoV-2-related syndromes in the pediatric population continues to evolve. This guidance document reflects currently available evidence coupled with expert opinion, and will be revised as further evidence becomes available., (© 2020, American College of Rheumatology.) more...
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- 2021
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46. Cyclophosphamide use in treatment of refractory Kawasaki disease with coronary artery aneurysms.
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Halyabar O, Friedman KG, Sundel RP, Baker AL, Chang MH, Gould PW, Newburger JW, and Son MBF
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- Child, Preschool, Female, Humans, Infant, Male, Retrospective Studies, Coronary Aneurysm drug therapy, Coronary Aneurysm etiology, Cyclophosphamide therapeutic use, Mucocutaneous Lymph Node Syndrome complications
- Abstract
Background: Despite timely administration of IVIG, some patients with Kawasaki disease (KD) develop rapidly progressive or giant coronary artery aneurysms (CAA)., Case Presentation: We describe our experience using cyclophosphamide (CYC) for the treatment of such cases as well as a review of the literature on the use of CYC in KD. Through a retrospective chart review of our KD population, we identified ten children treated for KD with intravenous CYC (10 mg/kg/dose) for one or two doses. Seven patients were male, the median age was 2.0 years (range 4 months - 5 years). All patients received initial IVIG between day 4-10 of illness. Other anti-inflammatory treatments administered before CYC included second IVIG (n = 9), corticosteroids (n = 10), infliximab (n = 4), cyclosporine (n = 2), and anakinra (n = 1). Median illness day at administration of the first CYC dose was 22.5 days (range:10-36 days). The primary indication for treatment with CYC for all patients was large or giant CAA and/or rapid progression of CAA. Three patients received a second dose of CYC (10 mg/kg) for progressively enlarging CAA. CAA did not progress after final CYC treatment. One patient with a history of neutropenia in infancy developed severe neutropenia 9 days after treatment with CYC, which recovered without intervention or complications. No patient developed infections or other serious toxicity from CYC., Conclusion: In KD patients with severe and progressive enlargement of CAA despite anti-inflammatory therapy, CYC seemed to arrest further dilation and was well-tolerated. Future multicenter studies are needed to confirm our findings in this subgroup of KD patients. more...
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- 2021
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47. Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19.
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Feldstein LR, Tenforde MW, Friedman KG, Newhams M, Rose EB, Dapul H, Soma VL, Maddux AB, Mourani PM, Bowens C, Maamari M, Hall MW, Riggs BJ, Giuliano JS Jr, Singh AR, Li S, Kong M, Schuster JE, McLaughlin GE, Schwartz SP, Walker TC, Loftis LL, Hobbs CV, Halasa NB, Doymaz S, Babbitt CJ, Hume JR, Gertz SJ, Irby K, Clouser KN, Cvijanovich NZ, Bradford TT, Smith LS, Heidemann SM, Zackai SP, Wellnitz K, Nofziger RA, Horwitz SM, Carroll RW, Rowan CM, Tarquinio KM, Mack EH, Fitzgerald JC, Coates BM, Jackson AM, Young CC, Son MBF, Patel MM, Newburger JW, and Randolph AG more...
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- Adolescent, Age Factors, Biomarkers analysis, Child, Child, Preschool, Diagnosis, Differential, Female, Humans, Intensive Care Units, Pediatric, Male, Patient Acuity, Regression Analysis, Stroke Volume, United States, Young Adult, COVID-19 complications, COVID-19 diagnosis, COVID-19 physiopathology, COVID-19 therapy, Systemic Inflammatory Response Syndrome complications, Systemic Inflammatory Response Syndrome diagnosis, Systemic Inflammatory Response Syndrome physiopathology, Systemic Inflammatory Response Syndrome therapy
- Abstract
Importance: Refinement of criteria for multisystem inflammatory syndrome in children (MIS-C) may inform efforts to improve health outcomes., Objective: To compare clinical characteristics and outcomes of children and adolescents with MIS-C vs those with severe coronavirus disease 2019 (COVID-19)., Setting, Design, and Participants: Case series of 1116 patients aged younger than 21 years hospitalized between March 15 and October 31, 2020, at 66 US hospitals in 31 states. Final date of follow-up was January 5, 2021. Patients with MIS-C had fever, inflammation, multisystem involvement, and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase-polymerase chain reaction (RT-PCR) or antibody test results or recent exposure with no alternate diagnosis. Patients with COVID-19 had positive RT-PCR test results and severe organ system involvement., Exposure: SARS-CoV-2., Main Outcomes and Measures: Presenting symptoms, organ system complications, laboratory biomarkers, interventions, and clinical outcomes. Multivariable regression was used to compute adjusted risk ratios (aRRs) of factors associated with MIS-C vs COVID-19., Results: Of 1116 patients (median age, 9.7 years; 45% female), 539 (48%) were diagnosed with MIS-C and 577 (52%) with COVID-19. Compared with patients with COVID-19, patients with MIS-C were more likely to be 6 to 12 years old (40.8% vs 19.4%; absolute risk difference [RD], 21.4% [95% CI, 16.1%-26.7%]; aRR, 1.51 [95% CI, 1.33-1.72] vs 0-5 years) and non-Hispanic Black (32.3% vs 21.5%; RD, 10.8% [95% CI, 5.6%-16.0%]; aRR, 1.43 [95% CI, 1.17-1.76] vs White). Compared with patients with COVID-19, patients with MIS-C were more likely to have cardiorespiratory involvement (56.0% vs 8.8%; RD, 47.2% [95% CI, 42.4%-52.0%]; aRR, 2.99 [95% CI, 2.55-3.50] vs respiratory involvement), cardiovascular without respiratory involvement (10.6% vs 2.9%; RD, 7.7% [95% CI, 4.7%-10.6%]; aRR, 2.49 [95% CI, 2.05-3.02] vs respiratory involvement), and mucocutaneous without cardiorespiratory involvement (7.1% vs 2.3%; RD, 4.8% [95% CI, 2.3%-7.3%]; aRR, 2.29 [95% CI, 1.84-2.85] vs respiratory involvement). Patients with MIS-C had higher neutrophil to lymphocyte ratio (median, 6.4 vs 2.7, P < .001), higher C-reactive protein level (median, 152 mg/L vs 33 mg/L; P < .001), and lower platelet count (<150 ×103 cells/μL [212/523 {41%} vs 84/486 {17%}, P < .001]). A total of 398 patients (73.8%) with MIS-C and 253 (43.8%) with COVID-19 were admitted to the intensive care unit, and 10 (1.9%) with MIS-C and 8 (1.4%) with COVID-19 died during hospitalization. Among patients with MIS-C with reduced left ventricular systolic function (172/503, 34.2%) and coronary artery aneurysm (57/424, 13.4%), an estimated 91.0% (95% CI, 86.0%-94.7%) and 79.1% (95% CI, 67.1%-89.1%), respectively, normalized within 30 days., Conclusions and Relevance: This case series of patients with MIS-C and with COVID-19 identified patterns of clinical presentation and organ system involvement. These patterns may help differentiate between MIS-C and COVID-19. more...
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- 2021
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48. Cardiac manifestations in SARS-CoV-2-associated multisystem inflammatory syndrome in children: a comprehensive review and proposed clinical approach.
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Sperotto F, Friedman KG, Son MBF, VanderPluym CJ, Newburger JW, and Dionne A
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- Child, Critical Care statistics & numerical data, Humans, COVID-19 complications, Heart Diseases etiology, SARS-CoV-2, Systemic Inflammatory Response Syndrome complications
- Abstract
Initial reports on COVID-19 described children as largely spared from severe manifestations, with only 2-6% of children requiring intensive care treatment. However, since mid-April 2020, clusters of pediatric cases of severe systemic hyperinflammation and shock epidemiologically linked with COVID-19 have been reported. This condition was named as SARS-Cov-2-associated multisystem inflammatory syndrome in children and showed similarities to Kawasaki disease. Here, we present a narrative review of cases reported in literature and we discuss the clinical acute and follow-up management of these patients. Patients with SARS-Cov-2-associated multisystem inflammatory syndrome frequently presented with persistent fever, gastrointestinal symptoms, polymorphic rash, conjunctivitis, and mucosal changes. Elevated inflammatory markers and evidence of cytokine storm were frequently observed. A subset of these patients also presented with hypotension and shock (20-100%) from either acute myocardial dysfunction or systemic hyperinflammation/vasodilation. Coronary artery dilation or aneurysms have been described in 6-24%, and arrhythmias in 7-60%. Cardiac support, immunomodulation, and anticoagulation are the key aspects for the management of the acute phase. Long-term structured follow-up of these patients is required due to the unclear prognosis and risk of progression of cardiac manifestations.Conclusion: Multisystem inflammatory syndrome is a novel syndrome related to SARS-CoV-2 infection. Evidence is still scarce but rapidly emerging in the literature. Cardiac manifestations are frequent, including myocardial and coronary involvement, and need to be carefully identified and monitored over time. What is Known: • Multisystem inflammatory syndrome in children (MIS-C) has been described associated with SARS-CoV-2. What is New: • Patients with MIS-C often present with fever, gastrointestinal symptoms, and shock. • Cardiac involvement is found in a high proportion of these patients, including ventricular dysfunction, coronary artery dilation or aneurysm, and arrhythmias. • Management is based on expert consensus and includes cardiac support, immunomodulatory agents, and anticoagulation. • Long-term follow-up is required due to the unclear prognosis and risk of progression of cardiac manifestation. more...
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- 2021
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49. Distinct clinical and immunological features of SARS-CoV-2-induced multisystem inflammatory syndrome in children.
- Author
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Lee PY, Day-Lewis M, Henderson LA, Friedman KG, Lo J, Roberts JE, Lo MS, Platt CD, Chou J, Hoyt KJ, Baker AL, Banzon TM, Chang MH, Cohen E, de Ferranti SD, Dionne A, Habiballah S, Halyabar O, Hausmann JS, Hazen MM, Janssen E, Meidan E, Nelson RW, Nguyen AA, Sundel RP, Dedeoglu F, Nigrovic PA, Newburger JW, and Son MBF more...
- Subjects
- Adolescent, Biomarkers blood, COVID-19, Child, Child, Preschool, Female, Fibrin Fibrinogen Degradation Products metabolism, Humans, Infant, Interleukin-10 blood, Interleukin-6 blood, Macrophage Activation Syndrome blood, Macrophage Activation Syndrome diagnosis, Macrophage Activation Syndrome drug therapy, Macrophage Activation Syndrome immunology, Male, Mucocutaneous Lymph Node Syndrome blood, Mucocutaneous Lymph Node Syndrome diagnosis, Mucocutaneous Lymph Node Syndrome drug therapy, Mucocutaneous Lymph Node Syndrome immunology, Natriuretic Peptide, Brain blood, Retrospective Studies, SARS-CoV-2, Adrenal Cortex Hormones administration & dosage, Betacoronavirus metabolism, Immunoglobulins, Intravenous administration & dosage, Immunomodulation, Interleukin 1 Receptor Antagonist Protein administration & dosage, Systemic Inflammatory Response Syndrome blood, Systemic Inflammatory Response Syndrome diagnosis, Systemic Inflammatory Response Syndrome drug therapy, Systemic Inflammatory Response Syndrome immunology
- Abstract
BACKGROUNDPediatric SARS-CoV-2 infection can be complicated by a dangerous hyperinflammatory condition termed multisystem inflammatory syndrome in children (MIS-C). The clinical and immunologic spectrum of MIS-C and its relationship to other inflammatory conditions of childhood have not been studied in detail.METHODSWe retrospectively studied confirmed cases of MIS-C at our institution from March to June 2020. The clinical characteristics, laboratory studies, and treatment response were collected. Data were compared with historic cohorts of Kawasaki disease (KD) and macrophage activation syndrome (MAS).RESULTSTwenty-eight patients fulfilled the case definition of MIS-C. Median age at presentation was 9 years (range: 1 month to 17 years); 50% of patients had preexisting conditions. All patients had laboratory confirmation of SARS-CoV-2 infection. Seventeen patients (61%) required intensive care, including 7 patients (25%) who required inotrope support. Seven patients (25%) met criteria for complete or incomplete KD, and coronary abnormalities were found in 6 cases. Lymphopenia, thrombocytopenia, and elevation in inflammatory markers, D-dimer, B-type natriuretic peptide, IL-6, and IL-10 levels were common but not ubiquitous. Cytopenias distinguished MIS-C from KD and the degree of hyperferritinemia and pattern of cytokine production differed between MIS-C and MAS. Immunomodulatory therapy given to patients with MIS-C included intravenous immune globulin (IVIG) (71%), corticosteroids (61%), and anakinra (18%). Clinical and laboratory improvement were observed in all cases, including 6 cases that did not require immunomodulatory therapy. No mortality was recorded in this cohort.CONCLUSIONMIS-C encompasses a broad phenotypic spectrum with clinical and laboratory features distinct from KD and MAS.FUNDINGThis work was supported by the National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases; the National Institute of Allergy and Infectious Diseases; Rheumatology Research Foundation Investigator Awards and Medical Education Award; Boston Children's Hospital Faculty Career Development Awards; the McCance Family Foundation; and the Samara Jan Turkel Center. more...
- Published
- 2020
- Full Text
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50. Atrioventricular Block in Children With Multisystem Inflammatory Syndrome.
- Author
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Dionne A, Mah DY, Son MBF, Lee PY, Henderson L, Baker AL, de Ferranti SD, Fulton DR, Newburger JW, and Friedman KG
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- Adolescent, Atrioventricular Block diagnosis, Atrioventricular Block epidemiology, COVID-19, Child, Child, Preschool, Female, Follow-Up Studies, Humans, Infant, Infant, Newborn, Male, Pandemics, Retrospective Studies, Risk Factors, SARS-CoV-2, Young Adult, Atrioventricular Block etiology, Betacoronavirus, Coronavirus Infections complications, Pneumonia, Viral complications, Systemic Inflammatory Response Syndrome complications
- Abstract
Background: Children are at risk for multisystem inflammatory syndrome in children (MIS-C) after infection with severe acute respiratory syndrome coronavirus 2. Cardiovascular complications, including ventricular dysfunction and coronary dilation, are frequent, but there are limited data on arrhythmic complications., Methods: Retrospective cohort study of children and young adults aged ≤21 years admitted with MIS-C. Demographic characteristics, electrocardiogram (ECG) and echocardiogram findings, and hospital course were described., Results: Among 25 patients admitted with MIS-C (60% male; median age 9.7 [interquartile range 2.7-15.0] years), ECG anomalies were found in 14 (56%). First-degree atrioventricular block (AVB) was seen in 5 (20%) patients a median of 6 (interquartile range 5-8) days after onset of fever and progressed to second- or third-degree AVB in 4 patients. No patient required intervention for AVB. All patients with AVB were admitted to the ICU (before onset of AVB) and had ventricular dysfunction on echocardiograms. All patients with second- or third-degree AVB had elevated brain natriuretic peptide levels, whereas the patient with first-degree AVB had a normal brain natriuretic peptide level. No patient with AVB had an elevated troponin level. QTc prolongation was seen in 7 patients (28%), and nonspecific ST segment changes were seen in 14 patients (56%). Ectopic atrial tachycardia was observed in 1 patient, and none developed ventricular arrhythmias., Conclusions: Children with MIS-C are at risk for atrioventricular conduction disease, especially those who require ICU admission and have ventricular dysfunction. ECGs should be monitored for evidence of PR prolongation. Continuous telemetry may be required in patients with evidence of first-degree AVB because of risk of progression to high-grade AVB., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.) more...
- Published
- 2020
- Full Text
- View/download PDF
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