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Postdischarge Glucocorticoid Use and Clinical Outcomes of Multisystem Inflammatory Syndrome in Children

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To identify the key insights or developments described in this article
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Key Points

Question  What are 3-month outcomes in patients with multisystem inflammatory syndrome in children (MIS-C), and what factors are associated with use of glucocorticoids following discharge?

Findings  In this cohort study including 186 US children with MIS-C, severity of inpatient illness was not associated with duration of postdischarge glucocorticoid treatment; clinical outcomes were similar in patients prescribed shorter courses. Significant weight gain was common, but recurrent inflammation following hospital discharge was infrequent.

Meaning  The findings of this study suggest that glucocorticoid tapers of less than 3 weeks are likely sufficient to treat MIS-C following discharge; shortening tapers is an important goal to avoid morbidity.

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.

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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Accepted for Publication: September 28, 2022.

Published: November 11, 2022. doi:10.1001/jamanetworkopen.2022.41622

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Son MBF et al. JAMA Network Open.

Corresponding Author: Mary Beth F. Son, MD, Division of Immunology, Boston Children’s Hospital, 300 Longwood Ave, Boston, MA 02115 (marybeth.son@childrens.harvard.edu).

Author Contributions: Dr Son and Ms Berbert had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Son, Canny, Muscal, Prahalad, Zambrano, Randolph.

Acquisition, analysis, or interpretation of data: Berbert, Young, Dallas, Newhams, Chen, Ardoin, Basiaga, Canny, Crandall, Dhakal, Dhanrajani, Sagcal-Gironella, Hobbs, Huie, James, Jones, Kim, Lionetti, Mannion, Muscal, Prahalad, Schulert, Sexson Tejtel, Villacis-Nunez, Wu, Campbell, Patel, Randolph.

Drafting of the manuscript: Son, Berbert, Young, Jones, Prahalad, Schulert.

Critical revision of the manuscript for important intellectual content: Son, Berbert, Young, Dallas, Newhams, Chen, Ardoin, Basiaga, Canny, Crandall, Dhakal, Dhanrajani, Sagcal-Gironella, Hobbs, Huie, James, Kim, Lionetti, Mannion, Muscal, Prahalad, Schulert, Sexson Tejtel, Villacis-Nunez, Wu, Zambrano, Campbell, Patel, Randolph.

Statistical analysis: Berbert, Young, Chen, Ardoin.

Obtained funding: Zambrano, Patel, Randolph.

Administrative, technical, or material support: Son, Dallas, Newhams, Ardoin, Basiaga, Dhakal, Hobbs, Huie, Jones, Kim, Mannion, Schulert, Villacis-Nunez, Zambrano, Campbell, Randolph.

Supervision: Canny, Hobbs, Mannion, Zambrano, Campbell, Patel, Randolph.

Conflict of Interest Disclosures: Dr Son reported receiving grants from the Centers for Disease Control and Prevention (CDC), salary support from the Childhood Arthritis & Rheumatology Research Alliance (CARRA), and royalties from UpToDate during the conduct of the study. Dr Basiaga reported receiving grants from CARRA and the Sjögren’s Foundation outside the submitted work. Dr Canny reported receiving grants from Overcoming COVID-19 during the conduct of the study and receiving grants from the National Institutes of Health (NIH), CARRA/Arthritis Foundation, and the Arthritis National Research Foundation outside the submitted work. Dr Hobbs reported receiving personal fees from DYNAMED.com as a clinical database reviewer, and speaker fees from Biofire/Biomerieux (2021-2022) outside the submitted work. Dr Mannion reported receiving grants from the Rheumatology Research Foundation during the conduct of the study. Dr Muscal reported being a paid member of the Swedish Orphan Biovitrum advisory board outside the submitted work. Dr Prahalad reported receiving personal fees for serving on a committee from Novartis Pharmaceuticals outside the submitted work. Dr Schulert reported receiving personal fees from Swedish Orphan Biovitrum and Novartis outside the submitted work. Dr Sexson Tejtel reported receiving grants from the NIH outside the submitted work. Dr Randolph reported receiving grants from the NIH to Boston Children's Hospital, royalties from UpToDate, and nonfinancial support from Illumina Inc for reagents outside the submitted work. No other disclosures were reported.

Funding/Support: This study was funded by the CDC under contract 75D30120C07725 to Boston Children’s Hospital.

Role of the Funder/Sponsor: The CDC technical staff were coinvestigators involved in the design and conduct of the study; interpretation of the data; preparation, review, and approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: The Overcoming COVID-19 Investigators are listed in Supplement 2.

Disclaimer: The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the CDC.

References
1.
Feldstein  LR , Rose  EB , Horwitz  SM ,  et al; Overcoming COVID-19 Investigators; CDC COVID-19 Response Team.  Multisystem Inflammatory syndrome in US children and adolescents.   N Engl J Med. 2020;383(4):334-346. doi:10.1056/NEJMoa2021680 PubMedGoogle ScholarCrossref
2.
McCrindle  BW , Rowley  AH , Newburger  JW ,  et al; American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Surgery and Anesthesia; and Council on Epidemiology and Prevention.  Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for health professionals from the American Heart Association.   Circulation. 2017;135(17):e927-e999. doi:10.1161/CIR.0000000000000484 PubMedGoogle ScholarCrossref
3.
Verdoni  L , Mazza  A , Gervasoni  A ,  et al.  An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study.   Lancet. 2020;395(10239):1771-1778. doi:10.1016/S0140-6736(20)31103-X PubMedGoogle ScholarCrossref
4.
Toubiana  J , Poirault  C , Corsia  A ,  et al.  Kawasaki-like multisystem inflammatory syndrome in children during the COVID-19 pandemic in Paris, France: prospective observational study.   BMJ. 2020;369:m2094. doi:10.1136/bmj.m2094 PubMedGoogle ScholarCrossref
5.
Lee  PY , Day-Lewis  M , Henderson  LA ,  et al.  Distinct clinical and immunological features of SARS-CoV-2–induced multisystem inflammatory syndrome in children.   J Clin Invest. 2020;130(11):5942-5950. doi:10.1172/JCI141113 PubMedGoogle ScholarCrossref
6.
Corwin  DJ , Sartori  LF , Chiotos  K ,  et al.  Distinguishing multisystem inflammatory syndrome in children from Kawasaki disease and benign inflammatory illnesses in the SARS-CoV-2 pandemic.   Pediatr Emerg Care. 2020;36(11):554-558. doi:10.1097/PEC.0000000000002248 PubMedGoogle ScholarCrossref
7.
Jonat  B , Gorelik  M , Boneparth  A ,  et al.  Multisystem inflammatory syndrome in children associated with coronavirus disease 2019 in a children’s hospital in New York City: patient characteristics and an institutional protocol for evaluation, management, and follow-up.   Pediatr Crit Care Med. 2021;22(3):e178-e191. doi:10.1097/PCC.0000000000002598 PubMedGoogle ScholarCrossref
8.
Henderson  LA , Canna  SW , Friedman  KG ,  et al.  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.   Arthritis Rheumatol. 2022;74(4):e1-e20. doi:10.1002/art.42062 PubMedGoogle ScholarCrossref
9.
Harwood  R , Allin  B , Jones  CE ,  et al; PIMS-TS National Consensus Management Study Group.  A national consensus management pathway for paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS): results of a national Delphi process.   Lancet Child Adolesc Health. 2021;5(2):133-141. doi:10.1016/S2352-4642(20)30304-7 PubMedGoogle ScholarCrossref
10.
Newburger  JW , Takahashi  M , Burns  JC ,  et al.  The treatment of Kawasaki syndrome with intravenous gamma globulin.   N Engl J Med. 1986;315(6):341-347. doi:10.1056/NEJM198608073150601 PubMedGoogle ScholarCrossref
11.
Kobayashi  T , Saji  T , Otani  T ,  et al; RAISE study group investigators.  Efficacy of immunoglobulin plus prednisolone for prevention of coronary artery abnormalities in severe Kawasaki disease (RAISE study): a randomised, open-label, blinded-endpoints trial.   Lancet. 2012;379(9826):1613-1620. doi:10.1016/S0140-6736(11)61930-2 PubMedGoogle ScholarCrossref
12.
Son  MBF , Murray  N , Friedman  K ,  et al; Overcoming COVID-19 Investigators.  Multisystem inflammatory syndrome in children—initial therapy and outcomes.   N Engl J Med. 2021;385(1):23-34. doi:10.1056/NEJMoa2102605 PubMedGoogle ScholarCrossref
13.
Ouldali  N , Toubiana  J , Antona  D ,  et al; French Covid-19 Paediatric Inflammation Consortium.  Association of intravenous immunoglobulins plus methylprednisolone vs immunoglobulins alone with course of fever in multisystem inflammatory syndrome in children.   JAMA. 2021;325(9):855-864. doi:10.1001/jama.2021.0694 PubMedGoogle ScholarCrossref
14.
McArdle  AJ , Vito  O , Patel  H ,  et al; BATS Consortium.  Treatment of multisystem inflammatory syndrome in children.   N Engl J Med. 2021;385(1):11-22. doi:10.1056/NEJMoa2102968 PubMedGoogle ScholarCrossref
15.
Villacis-Nunez  DS , Jones  K , Jabbar  A ,  et al.  Short-term outcomes of corticosteroid monotherapy in multisystem inflammatory syndrome in children.   JAMA Pediatr. 2022;176(6):576-584. doi:10.1001/jamapediatrics.2022.0292 Google ScholarCrossref
16.
Mahmoud  S , El-Kalliny  M , Kotby  A , El-Ganzoury  M , Fouda  E , Ibrahim  H .  Treatment of MIS-C in children and adolescents.   Curr Pediatr Rep. 2022;10(1):1-10. doi:10.1007/s40124-021-00259-4 PubMedGoogle ScholarCrossref
17.
Chou  J , Thomas  PG , Randolph  AG .  Immunology of SARS-CoV-2 infection in children.   Nat Immunol. 2022;23(2):177-185. doi:10.1038/s41590-021-01123-9 PubMedGoogle ScholarCrossref
18.
Kobayashi  T , Kobayashi  T , Morikawa  A ,  et al.  Efficacy of intravenous immunoglobulin combined with prednisolone following resistance to initial intravenous immunoglobulin treatment of acute Kawasaki disease.   J Pediatr. 2013;163(2):521-526. doi:10.1016/j.jpeds.2013.01.022 PubMedGoogle ScholarCrossref
19.
Weiss  PF , Feinstein  JA , Luan  X , Burnham  JM , Feudtner  C .  Effects of corticosteroid on Henoch-Schönlein purpura: a systematic review.   Pediatrics. 2007;120(5):1079-1087. doi:10.1542/peds.2007-0667 PubMedGoogle ScholarCrossref
20.
Leung  AKC , Barankin  B , Leong  KF .  Henoch-Schönlein purpura in children: an updated review.   Curr Pediatr Rev. 2020;16(4):265-276. doi:10.2174/18756336MTA2lNDYc2 PubMedGoogle ScholarCrossref
21.
Aljebab  F , Choonara  I , Conroy  S .  Systematic review of the toxicity of long-course oral corticosteroids in children.   PLoS One. 2017;12(1):e0170259. doi:10.1371/journal.pone.0170259 PubMedGoogle ScholarCrossref
22.
von Elm  E , Altman  DG , Egger  M , Pocock  SJ , Gøtzsche  PC , Vandenbroucke  JP ; STROBE Initiative.  The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.   J Clin Epidemiol. 2008;61(4):344-349. doi:10.1016/j.jclinepi.2007.11.008 PubMedGoogle ScholarCrossref
23.
Electronic Code of Federal Regulations Part 46—Protection of Human Subjects. 2017. Federal Policy for the Protection of Human Subjects. Accessed October 7, 2022. https://www.federalregister.gov/documents/2017/01/19/2017-01058/federal-policy-for-the-protection-of-human-subjects
24.
Novelli  L , Motta  F , De Santis  M , Ansari  AA , Gershwin  ME , Selmi  C .  The JANUS of chronic inflammatory and autoimmune diseases onset during COVID-19—a systematic review of the literature.   J Autoimmun. 2021;117:102592. doi:10.1016/j.jaut.2020.102592 PubMedGoogle ScholarCrossref
25.
Lee  PY , Platt  CD , Weeks  S ,  et al.  Immune dysregulation and multisystem inflammatory syndrome in children (MIS-C) in individuals with haploinsufficiency of SOCS1.   J Allergy Clin Immunol. 2020;146(5):1194-1200.e1. doi:10.1016/j.jaci.2020.07.033 PubMedGoogle ScholarCrossref
26.
Bhattacharjee  S , Banerjee  M .  Immune thrombocytopenia secondary to COVID-19: a systematic review.   SN Compr Clin Med. 2020;2(11):2048-2058. doi:10.1007/s42399-020-00521-8 PubMedGoogle ScholarCrossref
27.
Barrett  CE , Koyama  AK , Alvarez  P ,  et al.  Risk for newly diagnosed diabetes >30 days after SARS-CoV-2 infection among persons aged <18 years—United States, March 1, 2020-June 28, 2021.   MMWR Morb Mortal Wkly Rep. 2022;71(2):59-65. doi:10.15585/mmwr.mm7102e2 PubMedGoogle ScholarCrossref
28.
Truong  DT , Trachtenberg  FL , Pearson  GD ,  et al; MUSIC Study Investigators (Supplement 1).  The NHLBI Study on Long-terM OUtcomes after the Multisystem Inflammatory Syndrome In Children (MUSIC): Design and Objectives.   Am Heart J. 2022;243:43-53. doi:10.1016/j.ahj.2021.08.003PubMedGoogle ScholarCrossref
29.
Centers for Disease Control and Prevention. BMI percentile calculator for child and teen. 2022. Accessed April 27, 2022. https://www.cdc.gov/healthyweight/bmi/calculator.html
30.
Feldstein  LR , Tenforde  MW , Friedman  KG ,  et al; Overcoming COVID-19 Investigators.  Characteristics and outcomes of US children and adolescents with multisystem inflammatory syndrome in children (MIS-C) compared with severe acute COVID-19.   JAMA. 2021;325(11):1074-1087. doi:10.1001/jama.2021.2091 PubMedGoogle ScholarCrossref
31.
World Health Organization. Clinical management of COVID-19 patients: living guideline. September 14, 2022. Accessed October 7, 2022. https://app.magicapp.org/#/guideline/j1WBYn
32.
Multisystem inflammatory syndrome therapies in children (MISTIC) comparative effectiveness study. April 6, 2022. Accessed September 15, 2022. https://clinicaltrials.gov/ct2/show/NCT04898231
33.
Ringold  S , Nigrovic  PA , Feldman  BM ,  et al.  The Childhood Arthritis and Rheumatology Research Alliance Consensus treatment plans: toward comparative effectiveness in the pediatric rheumatic diseases.   Arthritis Rheumatol. 2018;70(5):669-678. doi:10.1002/art.40395 PubMedGoogle ScholarCrossref
34.
Levy  N , Koppel  JH , Kaplan  O ,  et al.  Severity and incidence of multisystem inflammatory syndrome in children during 3 SARS-CoV-2 pandemic waves in Israel.   JAMA. 2022;327(24):2452-2454. doi:10.1001/jama.2022.8025 PubMedGoogle ScholarCrossref
35.
Cloete  J , Kruger  A , Masha  M ,  et al.  Paediatric hospitalisations due to COVID-19 during the first SARS-CoV-2 Omicron (B.1.1.529) variant wave in South Africa: a multicentre observational study.   Lancet Child Adolesc Health. 2022;6(5):294-302. doi:10.1016/S2352-4642(22)00027-X PubMedGoogle ScholarCrossref
36.
Holm  M , Espenhain  L , Glenthøj  J ,  et al.  Risk and phenotype of multisystem inflammatory syndrome in vaccinated and unvaccinated Danish children before and during the Omicron wave.   JAMA Pediatr. 2022;176(8):821-823. doi:10.1001/jamapediatrics.2022.2206 PubMedGoogle ScholarCrossref
37.
Srinivasan  V .  Stress hyperglycemia in pediatric critical illness: the intensive care unit adds to the stress!   J Diabetes Sci Technol. 2012;6(1):37-47. doi:10.1177/193229681200600106 PubMedGoogle ScholarCrossref
38.
Tillotson  CV , Bowden  SA , Boktor  SW . Pediatric type 2 diabetes mellitus. StatPearls Publishing; 2022.
39.
Dufort  EM , Koumans  EH , Chow  EJ ,  et al; New York State and Centers for Disease Control and Prevention Multisystem Inflammatory Syndrome in Children Investigation Team.  Multisystem inflammatory syndrome in children in New York State.   N Engl J Med. 2020;383(4):347-358. doi:10.1056/NEJMoa2021756 PubMedGoogle ScholarCrossref
40.
Whittaker  E , Bamford  A , Kenny  J ,  et al; PIMS-TS Study Group and EUCLIDS and PERFORM Consortia.  Clinical characteristics of 58 children with a pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2.   JAMA. 2020;324(3):259-269. doi:10.1001/jama.2020.10369 PubMedGoogle ScholarCrossref
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