Research on gamma globulin unresponsive Kawasaki disease: A review

doi:10.5409/wjcp.v14.i4.108520

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World Journal of Clinical Pediatrics

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2219-2808

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Clin Pediatr. Dec 9, 2025; 14(4): 108520
Published online Dec 9, 2025. doi: 10.5409/wjcp.v14.i4.108520

Research on gamma globulin unresponsive Kawasaki disease: A review

Zu-Chuang Wu, Yan Pan

Zu-Chuang Wu, Yan Pan, Department of Pediatrics, The First Affiliated Hospital of Yangtze University, Jingzhou 434000, Hubei Province, China

Zu-Chuang Wu, Department of Pediatics, The Fifth Central Hospital of Tianjin, Tianjin 300450, China

Author contributions: Wu ZC performed research, analyzed data, and wrote the paper; Pan Y designed research, contributed new analytic tools, and modify the paper; Both authors participated in manuscript revision and communication with editors.

Conflict-of-interest statement: All authors declare that they have no conflict of interest to disclose.

Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

Corresponding author: Yan Pan, Researcher, Department of Pediatrics, The First Affiliated Hospital of Yangtze University, No. 55 Jianghan North Road, Shashi District, Jingzhou 434000, Hubei Province, China. woshipanyan@126.com

Received: April 17, 2025
Revised: May 14, 2025
Accepted: August 13, 2025
Published online: December 9, 2025
Processing time: 198 Days and 7.5 Hours

Abstract

Kawasaki disease (KD) is an acute, self-limited systemic vasculitis that primarily affects children. Treating nonresponding KD with intravenous immunoglobulin (IVIG) presents numerous challenges. This article comprehensively reviews the basic theory, clinical manifestations and diagnosis, treatment strategies, disputes and challenges, historical evolution and current situation, and future research directions of immunoglobulin unresponsive KD. In terms of basic theory, the epidemiological characteristics of KD, the mechanism of IVIG action, and the pathophysiological mechanism of the nonresponsive type are elaborated. In the clinical manifestation and diagnosis section, symptoms, diagnostic criteria, and imaging applications are analyzed. The treatment strategy encompasses drug, nondrug and individualized therapy. Controversies and challenges focus on diagnostic difficulties, treatment disputes, and long-term prognosis research. The historical evolution and current situation review the changes in treatment strategies and the current state of affairs. Future research directions anticipate the role of new therapeutic drug research and development, breakthroughs in basic research, and international cooperation, aiming to provide a comprehensive reference for research and clinical practice in this field.

Keywords: Kawasaki disease; Intravenous immunoglobulin resistance; Biomarkers; Immunomodulation; Coronary artery lesions

Core Tip: Gamma globulin-unresponsive Kawasaki disease (KD) poses significant clinical challenges due to its complex pathophysiology and variable treatment outcomes. This review synthesizes current knowledge on epidemiology, intravenous immunoglobulin resistance mechanisms, diagnostic criteria, and evolving therapeutic strategies (e.g., corticosteroids, biologics). Key controversies include optimal second-line therapies and long-term cardiovascular monitoring. Future directions emphasize targeted drug development and international collaboration to improve management of refractory KD.