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川崎病(小児科)

著者: 林泰佑 国立研究開発法人 国立成育医療研究センター 器官病態系内科部 循環器科

監修: 五十嵐隆 国立成育医療研究センター

著者校正/監修レビュー済:2021/06/09
患者向け説明資料

概要・推奨   

  1. 川崎病の初期治療として、ヒト免疫グロブリン大量療法単独による治療に対して、不応となるリスクが高いと推測される症例(γ-globulin療法開始前に群馬スコア、久留米スコア、大阪スコアにてリスクを評価する)に対しては、通常治療に加えてプレドニゾロン(2 mg/kg/day)を併用する(S、推奨度1)。
  1. 川崎病患者に対する治療は7病日以内に開始されていることが望ましい(J、推奨度1)。
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
林泰佑 : 特に申告事項無し[2021年]
監修:五十嵐隆 : 特に申告事項無し[2021年]

改訂のポイント:
  1. 日本小児循環器学会川崎病急性期治療のガイドライン(2020年改訂版)に基づき、急性期治療に関する記載を改めた。
  1. COVID-19 に続発する多系統炎症性症候群(MIS-C)に関する情報を記載した。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 川崎病とは、主に4歳以下の乳幼児(特に1歳前後)に好発する原因不明の急性熱性疾患で、病態は全身の中小動脈血管の炎症である。
  1. 患者発生には地域集積性および時間集積性が報告されるため、発症には感染症の関与が疑われている。
  1. 東洋人に多いことから、遺伝的要因が関わっている可能性も指摘されている。
  1. 第25回川崎病全国調査成績によると2018年の川崎病罹患率は0~4歳人口10万対359.1(男402.6、女313.4)であった。
  1. 同調査によると、同胞の川崎病罹患歴を有する例が2.1%、両親のいずれかに川崎病の既往歴があった例が1.3%であった。また、死亡例が5例あり(致命率0.03%)、うち4例は川崎病以外の原因による死亡であった。1例が動脈瘤破裂による死亡であり、死亡後の解剖や問診から川崎病と診断された。
 
問診・診察  
ポイント:
  1. 川崎病は、6つの主要症状のうち、経過中にいくつの症状が認められたかに基づいて診断する。したがって、問診と診察がもっとも重要である。

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文献 

著者: Francesca Sperotto, Kevin G Friedman, Mary Beth F Son, Christina J VanderPluym, Jane W Newburger, Audrey Dionne
雑誌名: Eur J Pediatr. 2021 Feb;180(2):307-322. doi: 10.1007/s00431-020-03766-6. Epub 2020 Aug 15.
Abstract/Text 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.

PMID 32803422  Eur J Pediatr. 2021 Feb;180(2):307-322. doi: 10.1007/s0・・・
著者: Tohru Kobayashi, Tsutomu Saji, Tetsuya Otani, Kazuo Takeuchi, Tetsuya Nakamura, Hirokazu Arakawa, Taichi Kato, Toshiro Hara, Kenji Hamaoka, Shunichi Ogawa, Masaru Miura, Yuichi Nomura, Shigeto Fuse, Fukiko Ichida, Mitsuru Seki, Ryuji Fukazawa, Chitose Ogawa, Kenji Furuno, Hirohide Tokunaga, Shinichi Takatsuki, Shinya Hara, Akihiro Morikawa, RAISE study group investigators
雑誌名: Lancet. 2012 Apr 28;379(9826):1613-20. doi: 10.1016/S0140-6736(11)61930-2. Epub 2012 Mar 8.
Abstract/Text BACKGROUND: Evidence indicates that corticosteroid therapy might be beneficial for the primary treatment of severe Kawasaki disease. We assessed whether addition of prednisolone to intravenous immunoglobulin with aspirin would reduce the incidence of coronary artery abnormalities in patients with severe Kawasaki disease.
METHODS: We did a multicentre, prospective, randomised, open-label, blinded-endpoints trial at 74 hospitals in Japan between Sept 29, 2008, and Dec 2, 2010. Patients with severe Kawasaki disease were randomly assigned by a minimisation method to receive either intravenous immunoglobulin (2 g/kg for 24 h and aspirin 30 mg/kg per day) or intravenous immunoglobulin plus prednisolone (the same intravenous immunoglobulin regimen as the intravenous immunoglobulin group plus prednisolone 2 mg/kg per day given over 15 days after concentrations of C-reactive protein normalised). Patients and treating physicians were unmasked to group allocation. The primary endpoint was incidence of coronary artery abnormalities during the study period. Analysis was by intention to treat. This trial is registered with the University Hospital Medical Information Network clinical trials registry, number UMIN000000940.
FINDINGS: We randomly assigned 125 patients to the intravenous immunoglobulin plus prednisolone group and 123 to the intravenous immunoglobulin group. Incidence of coronary artery abnormalities was significantly lower in the intravenous immunoglobulin plus prednisolone group than in the intravenous immunoglobulin group during the study period (four patients [3%] vs 28 patients [23%]; risk difference 0·20, 95% CI 0·12-0·28, p<0·0001). Serious adverse events were similar between both groups: two patients had high total cholesterol and one neutropenia in the intravenous immunoglobulin plus prednisolone group, and one had high total cholesterol and another non-occlusive thrombus in the intravenous immunoglobulin group.
INTERPRETATION: Addition of prednisolone to the standard regimen of intravenous immunoglobulin improves coronary artery outcomes in patients with severe Kawasaki disease in Japan. Further study of intensified primary treatment for this disease in a mixed ethnic population is warranted.
FUNDING: Japanese Ministry of Health, Labour and Welfare.

Copyright © 2012 Elsevier Ltd. All rights reserved.
PMID 22405251  Lancet. 2012 Apr 28;379(9826):1613-20. doi: 10.1016/S01・・・
著者: Jane W Newburger, Lynn A Sleeper, Brian W McCrindle, L LuAnn Minich, Welton Gersony, Victoria L Vetter, Andrew M Atz, Jennifer S Li, Masato Takahashi, Annette L Baker, Steven D Colan, Paul D Mitchell, Gloria L Klein, Robert P Sundel, Pediatric Heart Network Investigators
雑誌名: N Engl J Med. 2007 Feb 15;356(7):663-75. doi: 10.1056/NEJMoa061235.
Abstract/Text BACKGROUND: Treatment of acute Kawasaki disease with intravenous immune globulin and aspirin reduces the risk of coronary-artery abnormalities and systemic inflammation, but despite intravenous immune globulin therapy, coronary-artery abnormalities develop in some children. Studies have suggested that primary corticosteroid therapy might be beneficial and that adverse events are infrequent with short-term use.
METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial to determine whether the addition of intravenous methylprednisolone to conventional primary therapy for Kawasaki disease reduces the risk of coronary-artery abnormalities. Patients with 10 or fewer days of fever were randomly assigned to receive intravenous methylprednisolone, 30 mg per kilogram of body weight (101 patients), or placebo (98 patients). All patients then received conventional therapy with intravenous immune globulin, 2 g per kilogram, as well as aspirin, 80 to 100 mg per kilogram per day until they were afebrile for 48 hours and 3 to 5 mg per kilogram per day thereafter.
RESULTS: At week 1 and week 5 after randomization, patients in the two study groups had similar coronary dimensions, expressed as z scores adjusted for body-surface area, absolute dimensions, and changes in dimensions. As compared with patients receiving placebo, patients receiving intravenous methylprednisolone had a somewhat shorter initial period of hospitalization (P=0.05) and, at week 1, a lower erythrocyte sedimentation rate (P=0.02) and a tendency toward a lower C-reactive protein level (P=0.07). However, the two groups had similar numbers of days spent in the hospital, numbers of days of fever, rates of retreatment with intravenous immune globulin, and numbers of adverse events.
CONCLUSIONS: Our data do not provide support for the addition of a single pulsed dose of intravenous methylprednisolone to conventional intravenous immune globulin therapy for the routine primary treatment of children with Kawasaki disease. (ClinicalTrials.gov number, NCT00132080 [ClinicalTrials.gov].)

Copyright 2007 Massachusetts Medical Society.
PMID 17301297  N Engl J Med. 2007 Feb 15;356(7):663-75. doi: 10.1056/N・・・
著者: Hiromichi Hamada, Hiroyuki Suzuki, Yoshihiro Onouchi, Ryota Ebata, Masaru Terai, Shigeto Fuse, Yoshitomo Okajima, Shunji Kurotobi, Katsuki Hirai, Takashi Soga, Yukiko Ishiguchi, Yoshiaki Okuma, Nobuyuki Takada, Masaaki Yanai, Junichi Sato, Mami Nakayashiro, Mamoru Ayusawa, Eiichi Yamamoto, Yuichi Nomura, Yuya Hashimura, Kazunobu Ouchi, Hiroshi Masuda, Shinichi Takatsuki, Keiichi Hirono, Tadashi Ariga, Takashi Higaki, Akio Otsuki, Moe Terauchi, Reiko Aoyagi, Takatoshi Sato, Yasuhisa Fujii, Tadami Fujiwara, Hideki Hanaoka, Akira Hata, KAICA trial Investigators
雑誌名: Lancet. 2019 Mar 16;393(10176):1128-1137. doi: 10.1016/S0140-6736(18)32003-8. Epub 2019 Mar 7.
Abstract/Text BACKGROUND: Genetic studies have indicated possible involvement of the upregulated calcium-nuclear factor of activated T cells pathway in the pathogenesis of Kawasaki disease. We aimed to assess safety and efficacy of ciclosporin, an immunosuppressant targeting this pathway, for protection of patients with Kawasaki disease against coronary artery abnormalities.
METHODS: We did a randomised, open-label, blinded endpoints trial involving 22 hospitals in Japan between May 29, 2014, and Dec 27, 2016. Eligible patients predicted to be at higher risk for intravenous immunoglobulin (IVIG) resistance were randomly assigned to IVIG plus ciclosporin (5 mg/kg per day for 5 days; study treatment) or IVIG (conventional treatment) groups, stratified by risk score, age, and sex. The primary endpoint was incidence of coronary artery abnormalities using Japanese criteria during the 12-week trial, assessed in participants who received at least one dose of study drug and who visited the study institution at least once during treatment. This trial is registered to Center for Clinical Trials, Japan Medical Association, number JMA-IIA00174.
FINDINGS: We enrolled 175 participants. One patient withdrew consent after enrolment and was excluded and one patient (in the study treatment group) was excluded from analysis because of lost echocardiography data. Incidence of coronary artery abnormalities was lower in the study treatment group than in the conventional treatment group (12 [14%] of 86 patients vs 27 [31%] of 87 patients; risk ratio 0·46; 95% CI 0·25-0·86; p=0·010). No difference was found in the incidence of adverse events between the groups (9% vs 7%; p=0·78).
INTERPRETATION: Combined primary therapy with IVIG and ciclosporin was safe and effective for favourable coronary artery outcomes in Kawasaki disease patients who were predicted to be unresponsive to IVIG.
FUNDING: Japan Agency for Medical Research and Development (grant CCT-B-2503).

Copyright © 2019 Elsevier Ltd. All rights reserved.
PMID 30853151  Lancet. 2019 Mar 16;393(10176):1128-1137. doi: 10.1016/・・・
著者: Masaru Miura, Tohru Kobayashi, Toru Igarashi, Hiromichi Hamada, Naomi Iwata, Yoshifumi Sasaki, Miyuki Matsukawa, Noriko Sato, Hajime Kubo, Syuji Takei
雑誌名: Pediatr Infect Dis J. 2020 Jan;39(1):41-47. doi: 10.1097/INF.0000000000002503.
Abstract/Text BACKGROUND: In 2015, infliximab was approved for the treatment of patients with intravenous immunoglobulin-refractory Kawasaki disease (KD) in Japan. However, limited real-world data exist on the usefulness of infliximab for acute KD patients. We conducted a postmarketing surveillance study in patients with acute KD refractory to conventional therapies to evaluate the safety (including any live vaccine-related infections) and the effectiveness of infliximab.
METHODS: This was a multicenter, prospective, open-label, single-cohort, observational study in patients with acute KD refractory to conventional therapy who were prescribed a single 5 mg/kg dose of infliximab. Safety and effectiveness of infliximab were evaluated at 1 month, and live vaccine-related infections were further observed until 6 months from KD onset. Effectiveness assessments included fever resolution rate, the incidence of coronary artery lesions and change in coronary diameter Z scores.
RESULTS: A total of 291 patients were enrolled, and all patients completed the study. Adverse drug reactions and serious adverse drug reactions were reported in 12.4% and 3.1% of patients, respectively. Live vaccine-related infections were not observed. In the 208 patients with effectiveness assessments, the fever resolution rate within 48 hours after infliximab infusion was 77.4% (95% confidence interval: 71.1-82.9). Median time until fever resolution was 16.6 hours. After infliximab administration, the incidence (at baseline: 10.9%; at the final observation point: 12.0%; maximum value: 14.6%) and severity of coronary artery lesions did not change notably.
CONCLUSIONS: In this study, Infliximab for patients with acute KD refractory to conventional therapies was well tolerated and effective.

PMID 31815838  Pediatr Infect Dis J. 2020 Jan;39(1):41-47. doi: 10.109・・・

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