Analysis of Age, Sex, Lack of Response to Intravenous Immunoglobulin, and Development of Coronary Artery Abnormalities in Children With Kawasaki Disease in Japan

Takekoshi, Nobuhito; Kitano, Naomi; Takeuchi, Takashi; Suenaga, Tomohiro; Kakimoto, Nobuyuki; Suzuki, Takayuki; Kada, Tomoya Tsuchihashi; Shibuta, Shoichi; Tachibana, Shinya; Murayama, Yuri; Yamaga, Hiroo; Suzuki, Hiroyuki

doi:10.1001/jamanetworkopen.2022.16642

Cited by 6 publications

(5 citation statements)

References 37 publications

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“…Subsequent multivariable analysis identified age <1 year and pre‐ Z ‐max as independent risk factors for CAAs. The finding that age <1 year is a risk factor for CAA is consistent with previous studies 23–25 …”

Section: Discussionsupporting

confidence: 92%

“…The finding that age <1 year is a risk factor for CAA is consistent with previous studies. [23][24][25] Autopsy examinations have shown that changes in the coronary artery wall begin with inflammatory cell infiltration on the sixth to eighth days, whereas dilation begins from the 12th day. 26 Dilation of the coronary artery wall can likely occur earlier than the sixth to eighth days.…”

Section: Discussionmentioning

confidence: 99%

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Status of treatment and outcome in Kawasaki disease in the Kinki area of Japan

Tsuchihashi

Kakimoto

Kitano

et al. 2022

Pediatrics International

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Background The treatment guidelines for acute Kawasaki disease (KD) have been revised several times. Moreover, the criterion used to define coronary artery abnormalities (CAAs) has changed from the coronary artery's internal diameter to the Z‐score. Treatment for KD and methods for evaluating CAAs vary between hospitals, so we investigated the actual status of acute KD treatment and development of CAAs under the 2012 Japanese treatment guidelines for acute KD. Methods The 24th Japanese Nationwide Survey on Kawasaki Disease yielded 2618 patients who developed KD in the Kinki area in 2016. We sent a secondary questionnaire to each participating hospital and used the resulting data to investigate the frequency of CAAs according to Z‐score, treatment by KD treatment stage, and predictors of CAAs. Results The response rate was 80.0%. The data for 1426 patients without major data deficiencies were examined. The frequency of CAAs was 3.0% when based on coronary artery internal diameters and 8.8% when based on Z‐scores. Intravenous immunoglobulins combined with corticosteroids were administered as an initial treatment in 12.8% of cases and as a second‐line treatment in 16.8% of cases. Corticosteroids, cyclosporine A, infliximab, and plasma exchange were used at similar frequencies for third‐line treatment. A pretreatment maximum coronary artery Z‐score of ≥1.9 and age <1 year were associated with significantly higher incidences of CAAs. Conclusions Using the Z‐score resulted in a threefold increase in the number of patients diagnosed with CAAs. A pretreatment maximum coronary artery Z‐score of ≥1.9 and age <1 year are useful predictors of CAAs.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Status of treatment and outcome in Kawasaki disease in the Kinki area of Japan

Tsuchihashi

Kakimoto

Kitano

et al. 2022

Pediatrics International

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“…IVIG is the first-line treatment of KD with well-established therapeutic effects in preventing coronary artery abnormalities [ 41 ]. However, the criteria for when to provide IVIG are unclear and differ from the latest guidelines.…”

Section: Discussionmentioning

confidence: 99%

The therapeutic window of intravenous immunoglobulin (IVIG) and its correlation with clinical outcomes in Kawasaki disease: a systematic review and meta-analysis

Cai

Lü

et al. 2023

Ital J Pediatr

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Background The optimal therapeutic window to start intravenous immunoglobulin (IVIG) for Kawasaki disease (KD) is highly debatable. We aimed to summarize the existing literature to evaluate the therapeutic window of IVIG treatment and its correlation with clinical outcomes in KD patients. Methods We searched the databases from inception to August 26, 2022, without language restrictions. The primary outcomes were initial IVIG resistance and coronary artery lesions (CALs) in acute phase. Secondary outcome was CALs during 1–2 months of follow-up. Results 27 studies involving 41,139 patients were included in this study. Very low-quality evidence showed that the earlier IVIG treatment within 4 days had a higher IVIG-resistance rate (RR, 1.80; 95% CI, 1.50–2.15; P < .00001; I2 = 75%) than the late treatment. Very low-quality evidence showed that IVIG treatment for more than 7 days was associated with a higher risk of CALs in acute phase(RR, 0.57; 95% CI, 0.40–0.80; P = .001; I2 = 76%). There was a lower risk of CALs during 1–2 months follow-up for those who started IVIG administration within 10 days from the onset. Conclusions Overall, IVIG treatment within 7 days of illness seems to be the optimal therapeutic window of IVIG. IVIG treatment within 7 days is found to be effective for reducing the risk of coronary artery lesions and cardiac sequelae in KD patients. The early IVIG treatment within 4 days should be vigilant for the IVIG resistance although large multi-center randomized trials with well design are needed.

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“…Interestingly, the incidence of CAA was significantly different between sub-groups according to age and sex in selected patients when using the different scoring systems, which lends further support to the results of Kitano et al [ 38 ]. The different triggers, weak immune response, and immature coronary arteries of infants may contribute to the vulnerability to CAA formation in infants with KD even if they respond to initial IVIG treatment [ 40 ]; however, the real reason remains a mystery. Furthermore, a prospective study on 3,043 people aged 18–30 years revealed that the prevalence of coronary artery calcium was significantly higher in men than in women (15% vs. 5.1%) [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Risk Factors for Coronary Artery Aneurysm in a Chinese Pediatric Population with Kawasaki Disease at Low Risk of Intravenous Immunoglobulin Resistance: A Retrospective Cohort Study

Liu¹,

Su²,

Yuan³

et al. 2023

Cardiology

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Introduction: Multiple scoring systems for predicting intravenous immunoglobulin (IVIG) resistance have been developed. Although low-scoring patients with Kawasaki disease (KD) have a favorable prognosis, many develop coronary artery aneurysms (CAAs). Herein, we determined the risk factors for CAA development among patients with KD with low risk of IVIG resistance. Methods: We compared 14 scoring systems for predicting IVIG resistance among patients with KD hospitalized from 2003 to 2022. Patients were risk stratified using an optimal scoring system. Association between baseline characteristics and CAA development was assessed within the low-risk group. Results: Overall, 664 pediatric patients with KD were included; 108 (16.3%) had IVIG resistance, and the Liping scoring system had the highest area under the curve (0.714). According to this system, 444 (66.9%) patients with KD were classified as having low risk of developing IVIG resistance (<5 points). CAA development was significantly associated with male sex (odds ratio [OR], 1.946; 95% CI: 1.015–3.730), age <6 months at fever onset (OR, 3.142; 95% CI: 1.028–9.608), and a baseline maximum Z score of ≥2.72 (OR, 3.451; 95% CI: 2.582–4.612). CAA incidence increased with the number of risk factors, and comparisons with a Kobayashi score of <5 points among patients with KD revealed similar results. Conclusions: Predicting the response to IVIG might help further reduce CAA development in patients with KD.

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Analysis of Age, Sex, Lack of Response to Intravenous Immunoglobulin, and Development of Coronary Artery Abnormalities in Children With Kawasaki Disease in Japan

Cited by 6 publications

References 37 publications

Status of treatment and outcome in Kawasaki disease in the Kinki area of Japan

Status of treatment and outcome in Kawasaki disease in the Kinki area of Japan

The therapeutic window of intravenous immunoglobulin (IVIG) and its correlation with clinical outcomes in Kawasaki disease: a systematic review and meta-analysis

Risk Factors for Coronary Artery Aneurysm in a Chinese Pediatric Population with Kawasaki Disease at Low Risk of Intravenous Immunoglobulin Resistance: A Retrospective Cohort Study

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