The effects of early intravenous immunoglobulin therapy for Kawasaki disease: The 22nd nationwide survey in Japan

Kuwabara, Masanari; Yashiro, Mayumi; Ae, Ryusuke; Yanagawa, Hiroshi; Nakamura, Yosikazu

doi:10.1016/j.ijcard.2018.07.092

Cited by 16 publications

(21 citation statements)

References 19 publications

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“…Previous frequently reported risk factors for CAL, such as a higher platelet level, 27 , 28 a lower albumin level, 28 , 29 male sex, 6 , 28 – 30 IVIG resistance 6 , 29 , 31 and receiving initial IVIG beyond 10 days, 6 , 27 , 28 , 32 were also demonstrated in our findings. As for incomplete KD, study results were contradictory even in multivariate analyses.…”

Section: Discussionsupporting

confidence: 84%

Epidemiologic Features of Kawasaki Disease in Shanghai From 2013 Through 2017

Xie

Yan

Huang

et al. 2020

Journal of Epidemiology

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Background We sought to investigate epidemiologic features of Kawasaki disease (KD) in Shanghai from 2013 through 2017 and identify risk factors for coronary artery lesions (CAL). Methods As in our previous three surveys, a set of questionnaires and diagnostic guidelines for KD were sent to 50 hospitals providing pediatric medical care in Shanghai. Medical records of KD patients diagnosed from January 2013 through December 2017 were retrospectively analyzed. Multivariate logistic regression analysis was performed to identify risk factors for CAL. Results A total of 4,452 cases were enrolled. Male-to-female ratio was 1.7:1. The incidence of KD was 68.8 to 107.3 per 100,000 children aged <5 years from 2013 to 2017. Age at onset ranged from 15 days to 14.0 years (median: 1.8 years). KD occurred more frequently in spring and summer. Of 4,325 patients (97.0%) receiving intravenous immunoglobulin (IVIG), 362 (8.4%) were resistant to initial IVIG. CAL occurred in 406 (9.1%) patients, including 118 (2.7%) with medium aneurysms and 31 (0.7%) with giant aneurysms. Recurrent cases were 60 (1.3%). No death was found in this survey. Higher platelet levels, lower albumin levels, male sex, incomplete KD, IVIG resistance, and receiving initial IVIG ≤4 days or >10 days, were independently associated with CAL. Conclusions The incidence of KD in Shanghai had substantially increased while the proportion of CAL had substantially decreased as compared with our previous surveys. Higher platelet levels, lower albumin levels, male sex, incomplete KD, IVIG resistance, and receiving initial IVIG ≤4 days or >10 days, were risk factors for CAL.

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Section: Discussionsupporting

confidence: 84%

Epidemiologic Features of Kawasaki Disease in Shanghai From 2013 Through 2017

Xie

Yan

Huang

et al. 2020

Journal of Epidemiology

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“…It is important to analyze the risk factors for coronary lesions, and this has been done in a number of studies . It is also important to note, however, that the risk of cardiac complications cannot be fully analyzed in the nationwide survey, because the nationwide survey applies only to a 2 year period.…”

Section: Discussionmentioning

confidence: 99%

Nationwide epidemiologic survey of Kawasaki disease in Japan, 2015–2016

Makino

Nakamura

Yashiro

et al. 2019

Pediatrics International

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172

163

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Background: Approximately 50 years have passed since Kawasaki disease (KD) was first reported. The KD nationwide survey began in 1970. Although >360 000 cases have already been reported in Japan, the cause is still unknown. In Japan, the number of patients and incidence rate of KD has continued to increase. It is necessary to examine the trend of the occurrence in the surveillance of KD. Methods: The nationwide survey of patient incidence in 2015 and 2016 was conducted in 2017, as the 24th nationwide survey of KD. A questionnaire was sent to pediatric departments in hospitals with >100 beds and specialized pediatric hospitals, and was responded to by the attending pediatricians. Results: The total number of patients in 2 years was 31 595, and the sex ratio (male/female) was 1.34. The incidence rate (/100 000 children aged 0-4 years/year) was 330.2 (371.2 in boys, 287.3 in girls) in 2015, and 309.0 (343.2 in boys, 273.2 in girls) in 2016. The number of patients by month peaked in January. The age-specific incidence rate according to sex was highest in children between 9 and 11 months of age, after which the incidence rate gradually decreased with advancing age. Conclusions: We summarize the most recent nationwide survey of KD and consider the change in the epidemiologic picture.

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“…For instance, a combination of pulse corticosteroids and IVIG therapy has been shown to rescue patients with tocilizumab-resistant severe COVID-19 (96). High dose IVIG regimen (2 gm/Kg) is largely demonstrated as more effective (42,94), however, early IVIG therapy for KD within 4 days did not provide better protection from the development of CAL (97,98). Whether the earlier and higher doses of immunotherapy for MIS-C and KD responsible for better outcomes deserves further studies.…”

Section: Evolution Of Immunotherapies For Kd and Mis-cmentioning

confidence: 99%

Phenotype, Susceptibility, Autoimmunity, and Immunotherapy Between Kawasaki Disease and Coronavirus Disease-19 Associated Multisystem Inflammatory Syndrome in Children

et al. 2021

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Coronavirus disease-19 (COVID-19) in children is usually mild but some are susceptible to a Kawasaki disease (KD)-like multisystem inflammatory syndrome in children (MIS-C) in the convalescent stage, posing a need to differentiate the phenotype, susceptibility, autoimmunity, and immunotherapy between KD and MIS-C, particularly in the upcoming mass vaccination of COVID-19. Patients with MIS-C are prone to gastrointestinal symptoms, coagulopathy, and shock in addition to atypical KD syndrome with fever, mucocutaneous lesions, lymphadenopathy, and/or cardiovascular events. MIS-C manifests KD-like symptoms that alert physicians to early recognize and adopt the KD treatment regimen for patients with MIS-C. MIS-C linked to COVID-19 teaches us infection-associated autoimmune vasculitis and vice versa. Studies on genetic susceptibility have identified certain human leukocyte antigen (HLA) locus and toll-like receptor (TLR) associated with KD and/or COVID-19. Certain HLA subtypes, such as HLA-DRB1 and HLA-MICA A4 are associated with KD. HLA-B*46:01 is proposed to be the risk allele of severe COVID-19 infection, and blood group O type is a protective factor of COVID-19. The autoimmune vasculitis of KD, KD shock syndrome (KDSS), or MIS-C is mediated by a genetic variant of HLA, FcγR, and/or antibody-dependent enhancement (ADE) resulting in hyperinflammation with T helper 17 (Th17)/Treg imbalance with augmented Th17/Th1 mediators: interleukin-6 (IL-6), IL-10, inducible protein-10 (IP-10), Interferon (IFNγ), and IL-17A, and lower expression of Treg-signaling molecules, FoxP3, and transforming growth factor (TGF-β). There are certain similarities and differences in phenotypes, susceptibility, and pathogenesis of KD, KDSS, and MIS-C, by which a physician can make early protection, prevention, and precision treatment of the diseases. The evolution of immunotherapies for the diseases has shown that intravenous immunoglobulin (IVIG) alone or combined with corticosteroids is the standard treatment for KD, KDSS, and MIS-C. However, a certain portion of patients who revealed a treatment resistance to IVIG or IVIG plus corticosteroids, posing a need to early identify the immunopathogenesis, to protect hosts with genetic susceptibility, and to combat Th17/Treg imbalance by anti-cytokine or pro-Treg for reversal of the hyperinflammation and IVIG resistance. Based on physiological and pathological immunity of the diseases under genetic susceptibility and host milieu conditions, a series of sequential regimens are provided to develop a so-called “Know thyself, enemy (pathogen), and ever-victorious” strategy for the prevention and immunotherapy of KD and/or MIS-C.

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The effects of early intravenous immunoglobulin therapy for Kawasaki disease: The 22nd nationwide survey in Japan

Cited by 16 publications

References 19 publications

Epidemiologic Features of Kawasaki Disease in Shanghai From 2013 Through 2017

Epidemiologic Features of Kawasaki Disease in Shanghai From 2013 Through 2017

Nationwide epidemiologic survey of Kawasaki disease in Japan, 2015–2016

Phenotype, Susceptibility, Autoimmunity, and Immunotherapy Between Kawasaki Disease and Coronavirus Disease-19 Associated Multisystem Inflammatory Syndrome in Children

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