An Update on Reports of Atypical Presentations of Kawasaki Disease and the Recognition of IVIG Non-Responder Children

Abstract

Kawasaki disease (KD) is an acute vasculitis with an intrinsic risk of severe involvement of coronary arteries. The worldwide spread of KD and the importance of early diagnosis for preventing cardiovascular complications have ascertained the need for updating guidelines for prompt disease recognition and treatment efficacy assessment. All KD patients who comply with the definition of classic or atypical disease should be treated with intravenous immunoglobulin (IVIG) soon after diagnosis. The objective of our narrative review was to analyze the medical literature about case reports with atypical KD in relation to diagnosis and potential identification of predictors of non-responsiveness to IVIG. Our analysis has shown that the seminal challenge in KD management is the timeliness of diagnosis, although both extreme variability and transience of clinical manifestations make this goal difficult. A non-negligible percentage of patients, especially in the first 6 months of life, might have atypical manifestations of KD, whose painstaking differential diagnosis may be tricky. Many attempts to develop universal scoring systems and detect children at higher risk of IVIG resistance have been rather unsuccessful. Additionally, KD may show different evolutions according to unraveled demographic, genetic, or epigenetic factors. Further research is needed to elucidate all open questions about KD and clarify the long-term outcome of its potential complications.

Hypovitaminosis D and Leukocytosis to Predict Cardiovascular Abnormalities in Children with Kawasaki Disease: Insights from a Single-Center Retrospective Observational Cohort Study

“…Traditionally, the lack of defervescence within 24–36 h in children with an established diagnosis of KD after IVIG administration or the recurrence of fever after an initial response have been considered cues to recommend further second-line treatments [ 9 , 12 ]. Many attempts to develop universal scoring systems and detect children at higher risk of IVIG resistance have been unsuccessful, and KD may show a different evolution according to yet unraveled demographic, genetic, or epigenetic factors [ 13 ]. A network of genes orchestrating inflammatory machineries might be involved in the pathogenesis, development, and evolution of KD: several studies on gene expression and genome-wide associations in patients with KD have found that the most likely potential susceptibility genes are ITPKC , CASP3 , FCGR2A , and KCNN2 and have also confirmed that innate immunity pathways related to pathogen-associated molecular patterns of infectious agents and extracellular matrix components and proteins regulating their remodeling might be involved [ 14 ].…”

Clinical characteristics and correlation analysis of IVIG resistance in children with kawasaki disease complicated with hip synovitis: case-control study

“…Children with hip synovitis often have movement pain, limited walking, and synovial effusion but no noticeable swelling of the joint appearance ( 3 , 4 ). The treatment of KD has been relatively mature ( 5 , 6 ). A study in Japan showed that about 10%–20% of KD children did not respond to IVIG treatment ( 7 ), higher than that of children sensitive to IVIG treatment ( 8 ).…”