RARE DISEASE
Kawasaki disease
Kawasaki disease
Kawasaki disease
Synonyms: Mucocutaneous lymph node syndrome
Synonyms: Mucocutaneous lymph node syndrome
Synonyms: Mucocutaneous lymph node syndrome
Drug discovery
5
drugs
With orphan designations
Overview
Kawasaki disease (KD) is an acute, self-limiting vasculitis predominantly affecting children under 5 years, with potential coronary artery aneurysms (CAAs) in 25% of untreated cases [1][13]. Diagnosis requires ≥5 days of fever plus ≥4 of: bilateral conjunctivitis, oral mucosal changes, rash, extremity edema/erythema, and cervical lymphadenopathy [1][17]. Early treatment with intravenous immunoglobulin (IVIG) and aspirin reduces CAA risk to ~4% [5][13]. Refractory cases may require corticosteroids, TNF-α inhibitors, or other immunomodulators [1][5]. Long-term cardiovascular monitoring is critical for patients with CAAs [1][17].
Therapies
▪ First-line: IVIG (2 g/kg) + high-dose aspirin (80–100 mg/kg/day until afebrile) [1][11].
▪ Adjunctive therapies: Corticosteroids (for high-risk/refractory disease), TNF-α inhibitors (e.g., infliximab), or plasma exchange [5][15].
▪ Long-term: Low-dose aspirin (antiplatelet) ± anticoagulants for persistent aneurysms [3][13].
Categories: rare circulatory system diseases, rare systemic and rheumatological diseases, rare systemic or rheumatologic diseases of childhood
Research Papers
1,926 drug discovery papers about Kawasaki disease, with 4 first-in-class and 1 next-in-class emerging drug candidate forecasted to outperform the average preclinical success rate. Recent publications:
1,926 drug discovery papers about Kawasaki disease, with 4 first-in-class and 1 next-in-class emerging drug candidate forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-09-23 | Potential alternatives in treatment of kawasaki disease to reduce the extremely rare risk of reye syndrome.
Background/objective: Kawasaki disease is an acute, systemic vasculitis most commonly observed in young Asian children. While the exact pathogenesis remains unknown, it is thought to be triggered by a pathogenic exposure that elicits an inflammatory response several days to 2 weeks before the onset of symptoms. Symptoms include edematous hands and feet, conjunctivitis, mucositis, a diffuse erythematous rash, lymphadenopathy, and a fever lasting for at least 5 days, which is required for diagnosis. In addition, coronary vessels may exhibit aneurysms, thrombosis, and stenosis. Without treatment, Kawasaki disease carries a 25% risk of developing coronary aneurysms. However, with the timely administration of intravenous immunoglobulin, this risk is reduced to 4%. Given the inflammation and possible thrombosis of the coronary vasculature, current guidelines recommend aspirin for the management of Kawasaki disease. Kawasaki disease is one of the few conditions in which administering aspirin to children is considered acceptable, despite the risk of inducing Reye syndrome, a potentially fatal condition triggered by a viral infection while taking salicylates such as aspirin. Therefore, this review addresses a key question: why continue to use aspirin with its known risk of Reye syndrome when alternative antithrombotic drugs used in pediatric patients are available? This review seeks to explore potential substitutes for aspirin to mitigate the risk of Reye syndrome while also providing the necessary anticoagulation in Kawasaki disease.
2026-09-21 | Acute Coronary Syndrome in Kawasaki Disease From Infancy to Adulthood.
Acute coronary syndrome (ACS) remains underrecognized in patients with Kawasaki disease (KD). The population at risk for KD-associated ACS is increasing, yet current ACS guidelines are largely derived from atherosclerotic disease and do not adequately address the distinctive mechanisms, anatomy, and thrombosis risk associated with KD. Because the pathophysiology and management of KD-associated ACS differ in fundamental ways from those of atherosclerotic coronary artery disease, its management requires a coordinated team response, with collaboration between pediatric and adult cardiologists. Recent advances in coronary imaging, interventional techniques, and antithrombotic therapies provide an opportunity to establish a more disease-specific approach. This review synthesizes current evidence on the epidemiology and pathophysiology of coronary artery aneurysms, interventional coronary imaging, acute management, revascularization strategies, antithrombotic therapy, and post-ACS surveillance in patients with KD to guide clinical decision-making and treatment for patients with KD presenting with ACS.
2026-09-15 | Corticosteroids as adjunctive therapy to standard treatment in Kawasaki disease: a GRADE-assessed systematic review and meta-analysis of randomized controlled trials.
Kawasaki disease (KD) is an acute systemic vasculitis and the leading cause of acquired heart disease in children in developed countries. While IVIG plus aspirin remains standard treatment, 10-20% of patients are IVIG-resistant and face an elevated risk of coronary artery abnormalities. Corticosteroids have been explored as adjunctive therapy, though evidence on their benefit remains inconsistent. To assess the efficacy and safety of adjunctive corticosteroids in Kawasaki disease across key clinical outcomes. This PRISMA 2020-compliant systematic review and meta-analysis included RCTs identified through database searches up to April 2026. Risk of bias was assessed using Cochrane RoB 2.0. Data were pooled using random-effects models to estimate risk ratios (RRs) and mean differences (MDs) with 95% CIs. Subgroup analyses, leave-one-out sensitivity analyses, and GRADE certainty appraisal were also performed. Eight studies (n = 4106) were included. No significant differences were found in coronary artery abnormalities (CAA) within 1 month (RR 0.49, 95% CI 0.17-1.42), after 1 month (RR 0.81, 95% CI 0.43-1.55), fever duration (MD - 1.75, 95% CI - 3.71 to 0.21), or adverse events (RR 1.08, 95% CI 0.57-2.07). Hospital stay was modestly shorter with corticosteroids (MD - 0.99, 95% CI - 1.86 to - 0.11). Exploratory subgroup analyses suggested potential benefits with prednisolone-based and prolonged corticosteroid regimens for selected outcomes; however, these findings should be interpreted cautiously given multiple subgroup comparisons. Overall certainty of evidence was very low. Adjunctive corticosteroids did not significantly improve major outcomes in KD. Prednisolone-based regimens showed some promise, but high-quality trials are still needed before any firm conclusions can be drawn. • Corticosteroids have been studied as adjunctive therapy for Kawasaki disease, but their effects on coronary outcomes and other clinical outcomes remain inconsistent. • This meta-analysis found no significant improvement in major outcomes with adjunctive corticosteroids, although prednisolone-based and prolonged regimens may provide benefits for selected outcomes.
2026-09-11 | Association of the Aggregate Index of Systemic Inflammation with coronary artery aneurysm in Kawasaki disease patients.
Kawasaki disease (KD) is a common childhood disease that is prone to involve the coronary artery and may lead to coronary artery aneurysm (CAA). This study aimed to investigate the association between the Aggregate Index of Systemic Inflammation (AISI) with CAA in the acute phase KD. A total of 345 consecutive KD patients were enrolled in this study. To identify the independent risk factors for CAA, patient characteristics were compared using univariable analysis, followed by subsequent multivariable logistic regression analysis. Of 345 KD patients, 64 patients developed CAA. Multivariable logistic regression analysis showed that Age (OR 0.980; 95% CI, 0.966-0.985; P = 0.008), albumin (OR 0.937; 95% CI, 0.880-0.997; P = 0.040) and AISI/100 (OR 1.045; 95% CI, 1.003-1.089; P = 0.036) were independently associated with CAA in KD patients. According to the exploratory cutoff value of 711.58, AISI levels were divided into the low AISI group and the high AISI group. The incidence of CAA was significantly higher in KD patients with high AISI than in KD patients with low AISI(P < 0.001). The AISI was closely associated with CAA and served as a possible predictor of CAA in KD patients. This study aimed to investigate the association between the Aggregate Index of Systemic Inflammation with coronary artery aneurysm in the acute phase Kawasaki disease. The Aggregate Index of Systemic Inflammation was closely associated with coronary artery aneurysm and served as a possible predictor of coronary artery aneurysm in Kawasaki disease patients. Early identification based on the aggregate index of systemic inflammation may assist clinicians in implementing more aggressive treatment strategies (such as, IVIG combined with corticosteroids), thereby improving outcomes for patients with Kawasaki disease.
2026-09-01 | Continuous Renal Replacement Therapy for Cytokine Storm in Diabetic Kawasaki Shock Syndrome.
To report the successful use of continuous renal replacement therapy (CRRT) in a child with type 1 diabetes mellitus (T1DM) and intravenous immunoglobulin (IVIG)-refractory Kawasaki disease shock syndrome (KDSS). A 3-year, 10-month-old boy with poorly controlled T1DM and autoimmune thyroiditis presented with KDSS and diabetic ketoacidosis. Despite IVIG and high-dose aspirin, he developed refractory shock and metabolic acidosis. Continuous venovenous hemodiafiltration was initiated, leading to rapid hemodynamic stabilization, resolution of hyperinflammation, and metabolic normalization. CRRT may serve as a rescue therapy in critically ill children with concurrent cytokine storm and metabolic crisis, particularly when standard immunomodulatory therapies fail.
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2026-08-27 | Hepatobiliary involvement in Kawasaki disease: from cholestatic hepatitis to the hepatic vascular-biliary unit hypothesis-a state-of-the-art review.
This review provides a comprehensive synthesis of hepatobiliary involvement in Kawasaki disease (KD), with emphasis on cholestatic hepatitis as a clinical sentinel of hyperinflammation. We critically evaluate current evidence, propose an integrated pathogenic framework-the hepatic vascular-biliary unit injury hypothesis-and identify priority research areas. Narrative review of high-quality literature (2015-2025) with inclusion of seminal historical studies, using Oxford Centre for Evidence-Based Medicine (OCEBM) evidence-level grading. Cholestatic hepatitis occurs in 5.2%-17.8% of acute KD cases, rising to 22%-35% among intravenous immunoglobulin (IVIG)-resistant patients. Large retrospective cohort studies (OCEBM Level 3b) have identified a clinical "risk triangle" comprising IVIG resistance, coronary artery lesions (CALs), and cholestasis as interdependent factors. We propose the hepatic vascular-biliary unit injury hypothesis as an integrated pathogenic framework, supported by correlative pathological and molecular evidence (OCEBM Level 3-4), though causality remains unproven and requires validation in conditional endothelial-specific animal models. Current therapeutic evidence for moderate-to-severe cholestasis derives exclusively from retrospective cohorts and case series (OCEBM Level 3-4). Emerging evidence from Phase I/IIa trials supports the use of interleukin-1 blockade (anakinra) in refractory cases, predominantly derived from studies of coronary artery aneurysms rather than cholestasis-specific populations. KD-associated cholestatic hepatitis is a critical marker of disease severity with prognostic significance. The hepatic vascular-biliary unit hypothesis provides a mechanistic framework linking systemic vasculitis to cholestasis, pending experimental validation. Definitive evidence for optimal therapeutic strategies is lacking; well-designed randomized controlled trials specifically targeting the cholestasis subpopulation are urgently needed. Given the highest incidence in East Asian populations, clinicians in this region should maintain a particularly high index of suspicion for KD-associated cholestasis, particularly in infants presenting with unexplained jaundice.
2026-07-31 | Anakinra for intravenous immunoglobulin-resistant Kawasaki disease: a systematic literature review.
Approximately 10%-20% of patients with Kawasaki disease (KD) are resistant to intravenous immunoglobulins (IVIG) and are at increased risk of developing coronary artery aneurysms (CAA). A potential therapeutic role of anakinra (ANK) in refractory KD has been suggested. The aim of this work is to systematically review and critically appraise the available clinical evidence on the use of ANK in the treatment of IVIG-resistant KD, focusing on treatment indications, timing, dosage, efficacy on fever, inflammation, CAA and safety. A systematic literature search was conducted across PubMed, Embase, Web of Science, Cochrane Library, Emcare, Academic Search Premier and Google Scholar from inception to 9 October 2025, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Eligible studies included all study designs reporting outcomes of patients with KD treated with ANK. Thirty-two publications (31 identified through database search and one by cross-referencing) describing 81 patients were included. Most reports were single cases or small series, with two early-phase clinical trials. Treatment with ANK was associated with resolution of fever and systemic inflammation in 94.9% of patients. Complete CAA resolution was reported in 32% and stabilisation/dimensional reduction in 56.3%. No serious safety concerns were identified. However, these findings derive from heterogeneous and low-quality evidence and should be interpreted with caution. In IVIG-resistant KD, ANK was effective in controlling systemic inflammation, although more data are needed to assess its efficacy on coronary outcomes. While these findings are encouraging in supporting consideration of ANK for refractory KD, larger randomised clinical studies are warranted to define optimal ANK timing of introduction and dosing, and to evaluate its long-term efficacy on cardiac outcomes. CRD420252129435.
2026-07-28 | The Autophagy-Inflammasome Axis as a Molecular Switch: From Persistent Inflammation to Vascular Remodeling in IVIG-Resistant Kawasaki Disease.
Intravenous immunoglobulin (IVIG) resistance occurs in 10-20% of children with Kawasaki disease (KD) and is associated with a 3- to 5-fold higher risk of coronary artery lesions (CALs). Yet the mechanistic basis for why some patients progress from reversible inflammation to irreversible vascular damage after IVIG remains poorly understood. Most existing reviews have focused on risk prediction rather than the mechanistic chain linking resistance to CALs. Here, we synthesize current evidence across three interconnected pathways. First, autophagy dysfunction-particularly impaired mitophagy-sustains inflammation through cGAS-STING activation. Second, neutrophil extracellular traps (NETs) play a controversial role in KD vasculitis, with PAD2 and PAD4 possibly acting redundantly via the NLRP3 inflammasome. Third, endothelial-to-mesenchymal transition (EndMT), driven by the IL-1β/TNF axis and the USP7-TGFβ2/SMAD pathway, emerges as a core event in vascular remodeling. Building on these findings, we propose the "autophagy-inflammasome axis" as a candidate molecular switch that dictates whether inflammation resolves or persists. This hypothesis is actionable: it generates three explicit, testable predictions linking autophagic integrity to inflammatory outcomes and therapeutic response. Direct experimental validation in IVIG-resistant KD models and patient samples is now urgently needed. This review provides a systematic framework for understanding how IVIG resistance transitions to irreversible CALs. It also identifies candidate biomarkers (e.g., S100A12, mtDNA, and MCM8) and therapeutic targets (autophagy inducers, NLRP3 inhibitors, USP7 inhibitors, and anakinra) that could enable earlier intervention.
2026-05-31 | Vasculitis-associated aberrant apolipoprotein A2 = VAP2 and SDF-1α in Kawasaki disease patients with coronary artery lesion.
Kawasaki disease (KD) is an acute systemic vasculitis that predominantly affects the coronary arteries. The most serious complications are coronary artery lesions (CALs), including arterial dilatation, aneurysm, and stenosis, which occur in approximately 25% of untreated patients. Intravenous immunoglobulin (IVIG) therapy markedly reduces the incidence of CALs to 2-3%; however, the underlying mechanisms of IVIG's therapeutic effects remain unclear. Recently, we identified a recombinant single-chain fragment of the variable region of human immunoglobulin G, termed VasSF, which significantly ameliorated vasculitis in SCG/Kj mice. The VasSF-binding protein of 24 kDa (VAP2) was subsequently identified as an aberrant form of apolipoprotein A2 (ApoA2) in the serum of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. We investigated whether VAP2 and related ApoA2-derived molecules are associated with CAL formation in patients with KD. Baseline demographic and clinical characteristics were evaluated in 34 patients with KD during the acute and convalescent phases. Among them, 14 (41.2%) were initial IVIG non-responders, and 10 (29.4%) developed CALs. Western blot analysis revealed that VAP2 and VasSF bound to 17-kDa serum molecules predominantly during the acute phase of KD. Notably, in the CAL group, VAP2 levels exhibited a significant correlation with stromal cell-derived factor-1α (SDF-1α) (r2 = 0.5700, p = 0.049) among 78 cytokines analyzed. VAP2 was identified as a target molecule of VasSF in association with SDF-1α in our study. Considering that VasSF has been proposed as a therapeutic candidate for ANCA-associated vasculitis through targeting of aberrant ApoA2, VasSF may likewise represent a potential therapeutic agent for KD.
2026-05-22 | Kawasaki disease complicated by macrophage activation syndrome treated with canakinumab.
An infant presented with macrophage activation syndrome as part of Kawasaki disease, and was first treated with canakinumab, followed by methylprednisolone and IVIG. Despite early treatment, giant coronary artery aneurysms developed transiently, questioning the singular role of IL-1 in KD.
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2026-09-10 | Treatment and Outcomes of Kawasaki Disease Over 40 Years.
Kawasaki disease (KD) is the leading cause of acquired heart disease in children in developed countries. Long-term prognosis depends on coronary sequelae, yet Western longitudinal data integrating acute-phase features, treatment, and long-term coronary outcomes remain limited. We conducted a longitudinal observational cohort study including consecutive children diagnosed with KD between 1982 and 2025 at a single tertiary pediatric referral center in Italy. All patients underwent clinical and echocardiographic assessment during the acute phase, followed by longitudinal annual follow-up. Coronary involvement (dilation or aneurysm) was assessed by echocardiography. Among 533 children (median age, 26 months; 59.8% male), 117 (22.0%) developed acute coronary involvement, including 27 aneurysms and 90 dilation. Intravenous immunoglobulin (IVIG) use increased from 53.3% in the 1980s to 99% after 2020. The highest rates of IVIG resistance (30.0%) and coronary lesions (27.2%) occurred between 2011 and 2020, followed by a decline in 2021-2025. Persistent coronary abnormalities were observed exclusively in patients with medium-giant aneurysms. Independent predictors of aneurysm were age less than 6 months (odds ratio [OR], 7.64), IVIG resistance (OR, 9.89), IVIG administration after day 10 (OR, 5.27), and pericardial effusion (OR, 3.16). No persistent coronary sequelae were observed in high-risk patients treated with interleukin-1 inhibitors. In this 40-year Italian cohort, coronary aneurysms were uncommon but exclusively determined long-term coronary sequelae. Younger age, delayed treatment or IVIG resistance, and pericardial effusion independently predicted aneurysm formation, highlighting major and potentially modifiable gaps in care delivery. These findings support specialist, risk-based management with prompt escalation to reduce long-term coronary morbidity.
2026-09-04 | Incomplete Kawasaki Disease Versus Non-severe Multisystem Inflammatory Syndrome in Children: Distinguishing Features from Contemporaneous Patients.
Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) share overlapping clinical features, making diagnosis challenging. We compared patients with incomplete KD to those with non-severe MIS-C to identify distinguishing characteristics. Patients were enrolled in the International KD Registry (01/2020-10/2023) from 40 centers across eight countries. Among 2146 MIS-C patients, 769 met criteria for non-severe confirmed MIS-C (no shock or ICU admission). Among 1358 KD patients, 146 met American Heart Association (AHA) criteria for confirmed incomplete KD and 372 were classified as unconfirmed incomplete KD. Demographics, clinical and laboratory features, treatment, and cardiac outcomes were compared. Non-severe MIS-C patients were significantly older (median 7.4 years) than both confirmed (2.3 years) and unconfirmed (2.5 years; p < 0.001) incomplete KD patients, and had different ethnic distributions with more Black and fewer East or South Asian patients. MIS-C patients had shorter fever duration, fewer classic KD features, and more gastrointestinal and respiratory symptoms. They demonstrated lower white blood cell counts but higher inflammatory markers and markers of organ dysfunction. Cardiac involvement differed: MIS-C patients had more myocardial dysfunction, including lower ejection fraction and higher cardiac biomarkers. Coronary artery involvement in MIS-C (median maximum z-score 1.3) was similar to unconfirmed incomplete KD (median z-score 1.3) but less than confirmed incomplete KD (median z-score 2.0; p < 0.01). Older age, distinct ethnicity, prominent gastrointestinal and respiratory symptoms, and multisystem inflammation with ventricular dysfunction but relatively less coronary artery involvement help distinguish non-severe MIS-C from incomplete KD.
2026-08-28 | Construction and subgroup validation of a predictive model for IVIG-resistance in kawasaki disease.
Kawasaki disease is an acute immune vasculitis, and intravenous immunoglobulin (IVIG) therapy was an important treatment method, although a small proportion of children exhibited IVIG resistance. Our study aimed to construct a risk model for Kawasaki disease with IVIG resistance and to validate it across different clinical characteristic subgroups, with the goal of optimizing personalized and precise management to improve patient outcomes. We first compared various factors between the groups with and without IVIG resistance. Then, we used LASSO analysis to screen for factors that significantly predicted outcomes. The selected factors were used to develop the risk model. We evaluated the model using ROC curves, calibration curves, and decision curve analysis, and conducted internal validation through 5-fold cross-validation. Finally, we performed subgroup analyses based on age, sex, and other factors. Through univariate analysis, LASSO analysis, and correlation analysis, we identified WBC, PLT, CRP, fever days, PLR, and ALT as key factors in constructing the risk model. The model achieved an area under the curve of 0.816 (95% CI: 0.775-0.857). Additionally, calibration curves, DCA, and 5-fold cross-validation demonstrated that the model had good predictive performance. The model's effectiveness was also satisfactory across various subgroups. Our study successfully constructed a risk model for Kawasaki disease with IVIG resistance in the Chinese population. The model demonstrated strong predictive ability and was validated across multiple subgroups, showing potential clinical application value.
2026-08-03 | Risk factors and long-term follow-up in acute Kawasaki disease patients with medium or large coronary artery aneurysms.
Kawasaki disease (KD) is a systemic vasculitis that affects children under the age of five. Comprehensive data on KD patients with medium or large CAA are limited. This study aims to investigate the risk factors and long-term follow-up of KD patients with medium or large CAA in a Chinese cohort. We performed a cohort study of 220 KD patients including 55 patients associated with medium or large CAA and 165 patients without coronary artery abnormality between January 2015 and April 2020. Univariate and multivariate logistic regression analyses were used to identify risk factors. All enrolled patients were followed up for more than 12 months. Days to initial IVIG treatment, IVIG resistance, albumin level and platelet count were independent risk factors for KD patients with medium or large CAA based on multivariate logistic regression analysis. At a mean follow-up duration of 49 months, CAA subgroup analysis showed that 19 medium CAA cases (54.3%) promisingly regressed to normal coronary artery diameter, with the constituent ratios of small, medium, and large CAA being 31.4%, 8.6%, and 5.7%, respectively. In contrast, none of large CAA subgroup returned to normal coronary arteries. The constituent ratio of small, medium and large CAA was 15.0%, 25.0% and 60.0%. Besides, we found that coronary thrombosis occurred in 11 acute-phase cases (20.0%; 2 in the medium CAA, 9 in the large CAA), which increased to 18 cases (32.7%; 5 in the medium CAA, 13 in the large CAA) at the end of follow-up. Days to initial IVIG treatment, IVIG resistance, albumin levels and platelet count were risk factors for KD patients with medium or large CAA. The prognosis of medium or large CAA is not ideal during a long-term follow-up, particularly for large CAA.
2026-07-28 | Pre-IVIG echocardiography enables targeted treatment in infants younger than 6 months with Kawasaki Disease : Echocardiography-based risk stratification in young infants with Kawasaki Disease.
The 2024 American Heart Association scientific statement suggests intensification therapy in infants younger than 6 months (< 6 months) with Kawasaki disease (KD) may be beneficial, but indications remain undefined. We hypothesized that pre-IVIG echocardiographic findings could identify infants < 6 months who do not require intensification beyond standard intravenous immunoglobulin (IVIG). This multicenter cohort study in Taiwan (2019-2023) included children with KD who underwent echocardiography before IVIG and received IVIG within 10 days of illness onset. Children receiving early intensification therapy were excluded. Participants were stratified as < 6 months or ≥ 6 months. Echocardiography was performed at four time points: pre-IVIG, days 11-42, weeks 7-8, and 3 months after KD onset. Among 398 children with KD, 44 (11.1%) were younger than 6 months. Infants < 6 months had higher coronary artery aneurysm (CAA) prevalence at diagnosis than older children (52.3% vs 28.5%; OR, 2.74 [95% CI, 1.45-5.18]; P = .001). IVIG within 7 days was associated with lower CAA risk in both groups. Among children with initially normal coronary dimensions, new CAA risk did not differ significantly between younger and older groups (4.8% vs 2.4%; P = .42). Among 21 infants < 6 months without initial CAA, none developed new CAA except one with KD shock syndrome. Pre-IVIG echocardiography may help identify infants < 6 months at low risk for subsequent CAA development with standard IVIG treatment. Given the observational nature of this study, larger prospective studies are warranted to confirm these findings. • Infants younger than 6 months with Kawasaki disease (KD) have elevated coronary artery aneurysm (CAA) risk. • The 2024 AHA scientific statement suggests intensification therapy may be beneficial in this age group, but clear indications remain undefined. • In infants younger than 6 months with KD and normal pre-IVIG coonary dimensions, new coronary artery aneurysms rarely developed during follow-up. • Pre-IVIG echocardiography may help identify infants <6 months at low risks for subsequent CAA development with standard IVIG treatment.
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2026-06-17 | [Effect of miR-155-5p regulating the TLR4/MAPK/NF-κB pathway on inflammatory response, coronary artery lesion and immune function in mice with Kawasaki disease].
To investigate the effect of miR-155-5p regulation of the TLR4/MAPK/NF-κB pathway on inflammatory response, coronary artery lesion, and immune function in mice with Kawasaki disease (KD). Sixty male BALB/C mice were randomly assigned to six groups (n=10 each): healthy, KD, miR-155-5p agomir, agomir-negative control (agomir-NC), miR-155-5p antagomir, and antagomir-negative control (antagomir-NC). KD models were established by intraperitoneal injection of Lactobacillus casei cell wall extract in all groups except the healthy group. Levels of interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α were measured by ELISA. Flow cytometry was used to determine the proportions of CD3+, CD4+, and CD8+ T lymphocyte subsets and the CD4+/CD8+ ratio. Coronary artery diameter was assessed by high-frequency ultrasound, and histopathological changes were observed by hematoxylin-eosin staining. Endothelial cell apoptosis in coronary tissue was detected with TUNEL staining. Expression levels of nuclear factor kappa-B (NF-κB) p65, phosphorylated NF-κB p65 (p-NF-κB p65), Toll-like receptor 4 (TLR4), and p38 mitogen-activated protein kinase (MAPK) proteins were analyzed by Western blot. Compared with the healthy group, the KD group showed coronary arterial wall thickening, endothelial shedding, extensive inflammatory cell infiltration, disordered smooth muscle layer arrangement, vascular dilation, and lumen stenosis. The miR-155-5p agomir group exhibited aggravated coronary inflammation, wall thickening, and lumen stenosis versus the KD group, whereas the miR-155-5p antagomir group showed attenuated inflammation and wall thickening, improved smooth muscle arrangement, and reduced stenosis. The KD group demonstrated increased IL-6, IL-1β, TNF-α, CD4+ T cell percentage, CD4+/CD8+ ratio, coronary artery diameter, endothelial apoptosis rate, and p-NF-κB p65, TLR4, and p38 MAPK protein expression compared to the healthy group (all P<0.05), with decreased CD3+ and CD8+ T cell percentages (P<0.05). No significant differences were observed among the KD, agomir-NC, and antagomir-NC groups. Compared with the KD group, the miR-155-5p agomir group showed further increased inflammatory cytokines (IL-6, IL-1β, and TNF-α), CD4+ T cell percentage, CD4+/CD8+ ratio, coronary diameter, endothelial apoptosis, and protein expression of p-NF-κB p65, TLR4, and p38 MAPK, while reduced CD3+ and CD8+ T cell percentages (all P<0.05). Conversely, the miR-155-5p antagomir group showed significant reductions in inflammatory cytokines, protein expression of p-NF-κB p65, TLR4, and p38 MAPK, CD4+ T cell percentage, CD4+/CD8+ ratio, coronary artery diameter, and endothelial apoptosis, as well as significant increases in CD3+ and CD8+ T cell percentages (all P<0.05). Overexpression of miR-155-5p exacerbates inflammatory response, coronary artery lesions, endothelial cell apoptosis, and immune dysfunction in KD, potentially through modulation of the TLR4/MAPK/NF-κB pathway. Inhibition of miR-155-5p may reverse these pathological changes.
2024-08-21 | LncRNAs in Kawasaki disease and Henoch-Schönlein purpura: mechanisms and clinical applications.
Kawasaki disease (KD) and Henoch-Schönlein purpura (HSP) are the two most predominant types of childhood vasculitis. In childhood vasculitis, factors such as lack of sensitive diagnostic indicators and adverse effects of drug therapy may cause multiorgan system involvement and complications and even death. Many studies suggest that long noncoding RNAs (lncRNAs) are involved in the mechanism of vasculitis development in children and can be used to diagnose or predict prognosis by lncRNAs. In existing drug therapies, lncRNAs are also involved in drug-mediated treatment mechanisms and are expected to improve drug toxicity. The aim of this review is to summarize the link between lncRNAs and the pathogenesis of KD and HSP. In addition, we review the potential applications of lncRNAs in multiple dimensions, such as diagnosis, treatment, and prognosis prediction. This review highlights that targeting lncRNAs may be a novel therapeutic strategy to improve and treat KD and HSP.
2023-11-08 | NFIL3 aggravates human coronary artery endothelial cell injury by promoting ITGAM transcription in Kawasaki disease.
High expression of nuclear factor interleukin-3 (NFIL3) and integrin Alpha M (ITGAM) was found in serum samples from Kawasaki disease (KD) patients through bioinformatics analysis. Hence, this study aimed to explore the biological functions of NFIL3 and ITGAM in KD serum-stimulated human coronary artery endothelial cells (HCAECs). The differentially-expressed genes in KD were analyzed through bioinformatics analysis. Serum samples were obtained from 18 KD patients and 18 healthy volunteers, followed by detection of NFIL3 and ITGAM levels in KD serum. After HCAECs were transfected with sh-NFIL3, sh-ITGAM, or sh-NFIL3 + oe-ITGAM and underwent 24-h KD serum stimulation, cell viability and apoptosis and the levels of inflammation-related factors were measured. The binding between NFIL3 and ITGAM was validated by dual-luciferase and chromatin immunoprecipitation (ChIP) assays. NFIL3 and ITGAM were up-regulated in serum from KD patients and KD serum-stimulated HCAECs. Down-regulation of NFIL3 or ITGAM inhibited KD serum-induced cell apoptosis and inflammatory response of HCAECs and promoted cell viability. Mechanistically, NFIL3 promoted ITGAM transcription level. Up-regulation of ITGAM reversed the improvement of NFIL3 down-regulation on KD serum-induced HCAEC injury. NFIL3 aggravated KD serum-induced HCAEC injury by promoting ITGAM transcription, which provided new insights into the treatment of KD.
2023-07-31 | MiR-223-3p affects the proliferation and apoptosis of HCAECs in Kawasaki disease by regulating the expression of FOXP3.
Kawasaki disease (KD) can lead to permanent damage to coronary structures, the pathogenesis of which remains unknown. This experiment was designed to investigate whether miR-223-3p secreted in the serum of KD patients affects the proliferation and apoptosis of HCAECs in KD by regulating FOXP3. Blood samples were collected in acute febrile phase of KD, after IVIG treatment, and from healthy controls. Transfected into HCAECs cells by synthetic FOXP3 siRNA/NC. A co-culture system was established between HCAECs cells transfected with FOXP3 siRNA/NC and THP1 cells added with three sera. Compared with the control group, the expressions of miR-223-3p, RORγt, and Th17 in serum of KD patients were significantly upregulated, and the expressions of TGF-β1, FOXP3 and Treg were significantly downregulated. At the same time, the levels of IL-6, IL-17, and IL-23 were significantly increased, and the levels of IL-10 and FOXP3 were significantly decreased. After IVIG treatment, the patient's above results were reversed. The serum of KD patients increased the expression of miR-223-3p and inhibited the expression of FOXP3 in HCAECs cells. IVIG serum is the opposite. Overexpression of miR-223-3p also promoted the apoptosis of HCAECs. In addition, serum from KD patients promoted apoptosis, whereas serum after IVIG treatment inhibited apoptosis. KD patient serum downregulated the expression of FOXP3, Bcl2, TGF-β1 and IL-10 in cells, and upregulated the expression of caspase3, Bax, IL-17, IL-6, and IL-23. The opposite results were obtained with IVIG-treated sera. miR-223-3p secreted in serum of KD patients can regulate the expression of FOXP3 and affect the proliferation, apoptosis, and inflammation of cells.
2023-07-19 | CircRNA7632 down-regulation alleviates endothelial cell dysfunction in Kawasaki disease via regulating IL-33 expression.
Kawasaki disease (KD) is a form of idiopathic vasculitis frequently accompanied by coronary artery lesions, which involves endothelial dysfunction. Recent studies have demonstrated that circular RNAs (circRNAs) are implicated in many cardiovascular diseases. However, few studies have examined the role of circRNAs on endothelial dysfunction in KD. In this study, we investigated the role of circ7632 on endothelial-mesenchymal transition (EndoMT) in KD and then explored the underlying mechanism. Children diagnosed with KD and age-matched healthy controls (HC) were included. Sera samples were collected. Primary human umbilical vein endothelial cells (HUVECs) were obtained and incubated with 15% HC and KD serum for 48 h. The mRNA and protein expression of mesenchymal markers vimentin and α-smooth muscle actin (α-SMA) and endothelial marker zonula occludens-1 (ZO-1) in HUVECs transfected with plasmid-circ7632 and si-circ7632 were detected by RT-qPCR and Western blot analysis. CCK8, scratch test, and migration test were performed to examine the effect of circ7632 on the cell proliferation and migration. The circ7632 level was higher in HUVECs treated by KD serum than in HUVECs treated with HC serum. Overexpression of circ7632 significantly increased vimentin and α-SMA expression, decreased ZO-1 expression, and also decreased cell proliferation. Down-regulation of circ7632 expression got the opposite results. RNA-seq analysis, and confirmatory experiment displayed that down-regulation of circ7632 decreased IL-33 expression, and IL-33 silencing mitigated KD serum-mediated EndoMT. Our study revealed that circ7632 level was elevated in KD serum-treated HUVECs. Circ7632 down-regulation could alleviate EndoMT likely through decreasing IL-33 expression. The circ7632 may become a potential therapeutic target for KD.
other
2026-04-24 | Overview of T-cell subsets and related cytokines in Kawasaki disease.
Kawasaki disease (KD) is an acute febrile inflammatory illness in children characterized by systemic vasculitis; the etiology and pathogenesis have not been fully clarified. In recent years, studies have shown that T cell-mediated immune abnormalities play an important role in the development of KD. This paper reviewed the dynamic changes of T cell subsets (e.g., Th1, Th17, Treg, etc.) and their regulatory mechanisms in KD, focusing on the molecular mechanisms of T cell-mediated cytokine storm, autoimmune response and vascular injury. In addition, this paper summarizes the research progress of T cell-targeted therapy in KD, which provides a new theoretical basis for the optimization of clinical intervention strategies. By systematically combing the roles and mechanisms of T cells in KD, aims to provide reference for further elucidation of its pathogenesis and development of novel therapeutic approaches. IMPACT: T cells exhibit different immune responses in physiological and pathological states. Different T cell subsets are functionally diverse. Different T cell subsets in patients with Kawasaki disease exhibit significant differences in activity that correlate with therapeutic efficacy. Studies of T cell subsets reveal potential immunotherapeutic targets and improve our understanding of Kawasaki disease.
2025-11-21 | Therapeutic Plasma Exchange Resolves Inflammation With Increased HSD11B1 in Kawasaki Disease.
Kawasaki disease (KD) is an acute inflammatory disorder in children. The important complication of coronary artery aneurysms occurs in treatment-resistant patients. Therapeutic plasma exchange (TPE) has been effective for some refractory KD. Here, we investigated the effectiveness of TPE and how the glucocorticoid amplifying enzyme, 11beta-hydroxysteroid dehydrogenase 1, is involved in the resolution of inflammation in refractory KD.
2025-07-08 | The Caveolin-1/nuclear factor kappa-B signalling pathway is involved in Kawasaki disease vasculitis induced by Lactobacillus casei cell wall extract.
Kawasaki disease (KD) is an acute vasculitis and its pathogenesis is complex. Caveolin-1 (Cav-1) is the main structural protein of caveolae and is involved in the pathogenesis of many vascular diseases. A clinical study revealed that the Cav-1 serum level in children significantly increases in the acute phase of KD, but the role of Cav-1 in KD is still unclear. We aimed to explore whether and how Cav-1 is involved in the KD pathogenesis. KD vasculitis was induced by Lactobacillus casei cell wall extract intraperitoneal injection in mice, and Cav-1 expression was inhibited by adeno-associated viruses (AAV)-Cav-1 shRNA. Cardiovascular lesions was assessed via haematoxylin and eosin staining. Proinflammatory cytokine and matrix metalloproteinase-9 levels were measured via quantitative real-time polymerase chain reaction. Endothelial cell adhesion molecule expression was evaluated by immunohistochemistry. Cav-1 expression and nuclear factor kappa-B pathway activation were evaluated by Western blotting. Mice with Lactobacillus casei cell wall extract-induced KD vasculitis exhibited severe heart vessel inflammation and increased Cav-1, proinflammatory cytokine, matrix metalloproteinase-9, and endothelial cell adhesion molecule expression, which were reversed after Cav-1 inhibition. Moreover, nuclear factor kappa-B activation of KD vasculitis model mice was suppressed after Cav-1 inhibition. Cav-1 participates in KD vasculitis pathogenesis by regulating the nuclear factor kappa-B signalling pathway.
2025-07-01 | Vaccine-associated Kawasaki disease in children
Kawasaki disease (KD) is a leading cause of heart disease in children. The etiology of KD is currently unknown. The onset of KD occurs with delays following pathogen outbreaks and also post-immunization. A recent etiology model of KD proposed that KD is caused by activation of mast cells and likely platelets. Recently, it was discovered that epilepsy safety signals were associated with specific vaccines for infants aged 0 and 1. The problem statement of this paper is whether these safety signals also appear in children post-immunization. Herein, the Vaccine Adverse Event Reporting System was retrospectively examined for KD adverse events (AEs) for children. The same pattern of safety signals was observed with KD AEs as epilepsy AEs post-immunization. KD associated with vaccination (KD-V) is associated with either a pattern consistent with direct innate immune activation or immune complex activation of mast cells and likely platelets. Candidate causative factors identified include live virus vaccines and very high dosage levels for specific infant vaccines and specific concomitant combinations. Adjusting vaccine dosage based on infant body size for several vaccines is strongly recommended, including adjusting the infectious units in attenuated live viral vaccines. Concomitant administration of specific vaccines results in either additive or synergy risk levels for KD. Concomitant administration of specific vaccines, including attenuated live viruses with synergy KD risk levels, is strongly recommended against (counterindicated).
2025-06-01 | Clinical Outcomes of Using Radial Artery for Coronary Artery Bypass Graft in Children With Kawasaki Disease.
To investigate the early clinical outcomes of using radial artery (RA) graft for coronary artery bypass graft (CABG) surgery in children with coronary sequelae of Kawasaki disease (KD). Clinical data of all 26 children (22 male, 4 female) with coronary sequelae of KD who underwent CABG with RA graft at our hospital between March 2016 and September 2023 were retrospectively analyzed. The severity of coronary artery lesions was classified as Va or Vb in all patients. The median (P25, P75) age of patients was 8.5 (6.0, 11.3) y and the median weight was 33.0 (21.0, 45.3) kg. The mean interval from diagnosis to operation was 5.4 ± 3.7 y. The median postoperative mechanical ventilation time was 6.0 (4.0, 12.3) h. The median intensive care unit stay was 2.0 (2.0, 3.3) d. The median length of postoperative hospital stay was 19.0 (13.0, 29.0) d. Postoperative follow-up time ranged from 0.2 to 5.8 y, and no cardiovascular-related complications occurred. Sixteen patients underwent cardiac catheterization or CT angiography during follow-up. One patient each had anastomotic stenosis in RA and right internal thoracic artery graft, respectively, while myocardial perfusion imaging showed no worsening of myocardial ischemia. There was no significant difference in forearm motor and sensory function between the operated and the contralateral arm; brachial artery angiography showed well-established forearm collateral vessels. CABG is a safe and effective treatment for KD with severe coronary lesions in children. The RA graft has good early patency without impairing forearm function. Individualized surgical and anticoagulant strategies may help improve the prognosis.
small molecules
2026-09-23 | Potential alternatives in treatment of kawasaki disease to reduce the extremely rare risk of reye syndrome.
Background/objective: Kawasaki disease is an acute, systemic vasculitis most commonly observed in young Asian children. While the exact pathogenesis remains unknown, it is thought to be triggered by a pathogenic exposure that elicits an inflammatory response several days to 2 weeks before the onset of symptoms. Symptoms include edematous hands and feet, conjunctivitis, mucositis, a diffuse erythematous rash, lymphadenopathy, and a fever lasting for at least 5 days, which is required for diagnosis. In addition, coronary vessels may exhibit aneurysms, thrombosis, and stenosis. Without treatment, Kawasaki disease carries a 25% risk of developing coronary aneurysms. However, with the timely administration of intravenous immunoglobulin, this risk is reduced to 4%. Given the inflammation and possible thrombosis of the coronary vasculature, current guidelines recommend aspirin for the management of Kawasaki disease. Kawasaki disease is one of the few conditions in which administering aspirin to children is considered acceptable, despite the risk of inducing Reye syndrome, a potentially fatal condition triggered by a viral infection while taking salicylates such as aspirin. Therefore, this review addresses a key question: why continue to use aspirin with its known risk of Reye syndrome when alternative antithrombotic drugs used in pediatric patients are available? This review seeks to explore potential substitutes for aspirin to mitigate the risk of Reye syndrome while also providing the necessary anticoagulation in Kawasaki disease.
2026-09-21 | Acute Coronary Syndrome in Kawasaki Disease From Infancy to Adulthood.
Acute coronary syndrome (ACS) remains underrecognized in patients with Kawasaki disease (KD). The population at risk for KD-associated ACS is increasing, yet current ACS guidelines are largely derived from atherosclerotic disease and do not adequately address the distinctive mechanisms, anatomy, and thrombosis risk associated with KD. Because the pathophysiology and management of KD-associated ACS differ in fundamental ways from those of atherosclerotic coronary artery disease, its management requires a coordinated team response, with collaboration between pediatric and adult cardiologists. Recent advances in coronary imaging, interventional techniques, and antithrombotic therapies provide an opportunity to establish a more disease-specific approach. This review synthesizes current evidence on the epidemiology and pathophysiology of coronary artery aneurysms, interventional coronary imaging, acute management, revascularization strategies, antithrombotic therapy, and post-ACS surveillance in patients with KD to guide clinical decision-making and treatment for patients with KD presenting with ACS.
2026-09-15 | Corticosteroids as adjunctive therapy to standard treatment in Kawasaki disease: a GRADE-assessed systematic review and meta-analysis of randomized controlled trials.
Kawasaki disease (KD) is an acute systemic vasculitis and the leading cause of acquired heart disease in children in developed countries. While IVIG plus aspirin remains standard treatment, 10-20% of patients are IVIG-resistant and face an elevated risk of coronary artery abnormalities. Corticosteroids have been explored as adjunctive therapy, though evidence on their benefit remains inconsistent. To assess the efficacy and safety of adjunctive corticosteroids in Kawasaki disease across key clinical outcomes. This PRISMA 2020-compliant systematic review and meta-analysis included RCTs identified through database searches up to April 2026. Risk of bias was assessed using Cochrane RoB 2.0. Data were pooled using random-effects models to estimate risk ratios (RRs) and mean differences (MDs) with 95% CIs. Subgroup analyses, leave-one-out sensitivity analyses, and GRADE certainty appraisal were also performed. Eight studies (n = 4106) were included. No significant differences were found in coronary artery abnormalities (CAA) within 1 month (RR 0.49, 95% CI 0.17-1.42), after 1 month (RR 0.81, 95% CI 0.43-1.55), fever duration (MD - 1.75, 95% CI - 3.71 to 0.21), or adverse events (RR 1.08, 95% CI 0.57-2.07). Hospital stay was modestly shorter with corticosteroids (MD - 0.99, 95% CI - 1.86 to - 0.11). Exploratory subgroup analyses suggested potential benefits with prednisolone-based and prolonged corticosteroid regimens for selected outcomes; however, these findings should be interpreted cautiously given multiple subgroup comparisons. Overall certainty of evidence was very low. Adjunctive corticosteroids did not significantly improve major outcomes in KD. Prednisolone-based regimens showed some promise, but high-quality trials are still needed before any firm conclusions can be drawn. • Corticosteroids have been studied as adjunctive therapy for Kawasaki disease, but their effects on coronary outcomes and other clinical outcomes remain inconsistent. • This meta-analysis found no significant improvement in major outcomes with adjunctive corticosteroids, although prednisolone-based and prolonged regimens may provide benefits for selected outcomes.
2026-09-11 | Association of the Aggregate Index of Systemic Inflammation with coronary artery aneurysm in Kawasaki disease patients.
Kawasaki disease (KD) is a common childhood disease that is prone to involve the coronary artery and may lead to coronary artery aneurysm (CAA). This study aimed to investigate the association between the Aggregate Index of Systemic Inflammation (AISI) with CAA in the acute phase KD. A total of 345 consecutive KD patients were enrolled in this study. To identify the independent risk factors for CAA, patient characteristics were compared using univariable analysis, followed by subsequent multivariable logistic regression analysis. Of 345 KD patients, 64 patients developed CAA. Multivariable logistic regression analysis showed that Age (OR 0.980; 95% CI, 0.966-0.985; P = 0.008), albumin (OR 0.937; 95% CI, 0.880-0.997; P = 0.040) and AISI/100 (OR 1.045; 95% CI, 1.003-1.089; P = 0.036) were independently associated with CAA in KD patients. According to the exploratory cutoff value of 711.58, AISI levels were divided into the low AISI group and the high AISI group. The incidence of CAA was significantly higher in KD patients with high AISI than in KD patients with low AISI(P < 0.001). The AISI was closely associated with CAA and served as a possible predictor of CAA in KD patients. This study aimed to investigate the association between the Aggregate Index of Systemic Inflammation with coronary artery aneurysm in the acute phase Kawasaki disease. The Aggregate Index of Systemic Inflammation was closely associated with coronary artery aneurysm and served as a possible predictor of coronary artery aneurysm in Kawasaki disease patients. Early identification based on the aggregate index of systemic inflammation may assist clinicians in implementing more aggressive treatment strategies (such as, IVIG combined with corticosteroids), thereby improving outcomes for patients with Kawasaki disease.
2026-09-01 | Continuous Renal Replacement Therapy for Cytokine Storm in Diabetic Kawasaki Shock Syndrome.
To report the successful use of continuous renal replacement therapy (CRRT) in a child with type 1 diabetes mellitus (T1DM) and intravenous immunoglobulin (IVIG)-refractory Kawasaki disease shock syndrome (KDSS). A 3-year, 10-month-old boy with poorly controlled T1DM and autoimmune thyroiditis presented with KDSS and diabetic ketoacidosis. Despite IVIG and high-dose aspirin, he developed refractory shock and metabolic acidosis. Continuous venovenous hemodiafiltration was initiated, leading to rapid hemodynamic stabilization, resolution of hyperinflammation, and metabolic normalization. CRRT may serve as a rescue therapy in critically ill children with concurrent cytokine storm and metabolic crisis, particularly when standard immunomodulatory therapies fail.
proteins
2026-08-27 | Hepatobiliary involvement in Kawasaki disease: from cholestatic hepatitis to the hepatic vascular-biliary unit hypothesis-a state-of-the-art review.
This review provides a comprehensive synthesis of hepatobiliary involvement in Kawasaki disease (KD), with emphasis on cholestatic hepatitis as a clinical sentinel of hyperinflammation. We critically evaluate current evidence, propose an integrated pathogenic framework-the hepatic vascular-biliary unit injury hypothesis-and identify priority research areas. Narrative review of high-quality literature (2015-2025) with inclusion of seminal historical studies, using Oxford Centre for Evidence-Based Medicine (OCEBM) evidence-level grading. Cholestatic hepatitis occurs in 5.2%-17.8% of acute KD cases, rising to 22%-35% among intravenous immunoglobulin (IVIG)-resistant patients. Large retrospective cohort studies (OCEBM Level 3b) have identified a clinical "risk triangle" comprising IVIG resistance, coronary artery lesions (CALs), and cholestasis as interdependent factors. We propose the hepatic vascular-biliary unit injury hypothesis as an integrated pathogenic framework, supported by correlative pathological and molecular evidence (OCEBM Level 3-4), though causality remains unproven and requires validation in conditional endothelial-specific animal models. Current therapeutic evidence for moderate-to-severe cholestasis derives exclusively from retrospective cohorts and case series (OCEBM Level 3-4). Emerging evidence from Phase I/IIa trials supports the use of interleukin-1 blockade (anakinra) in refractory cases, predominantly derived from studies of coronary artery aneurysms rather than cholestasis-specific populations. KD-associated cholestatic hepatitis is a critical marker of disease severity with prognostic significance. The hepatic vascular-biliary unit hypothesis provides a mechanistic framework linking systemic vasculitis to cholestasis, pending experimental validation. Definitive evidence for optimal therapeutic strategies is lacking; well-designed randomized controlled trials specifically targeting the cholestasis subpopulation are urgently needed. Given the highest incidence in East Asian populations, clinicians in this region should maintain a particularly high index of suspicion for KD-associated cholestasis, particularly in infants presenting with unexplained jaundice.
2026-07-31 | Anakinra for intravenous immunoglobulin-resistant Kawasaki disease: a systematic literature review.
Approximately 10%-20% of patients with Kawasaki disease (KD) are resistant to intravenous immunoglobulins (IVIG) and are at increased risk of developing coronary artery aneurysms (CAA). A potential therapeutic role of anakinra (ANK) in refractory KD has been suggested. The aim of this work is to systematically review and critically appraise the available clinical evidence on the use of ANK in the treatment of IVIG-resistant KD, focusing on treatment indications, timing, dosage, efficacy on fever, inflammation, CAA and safety. A systematic literature search was conducted across PubMed, Embase, Web of Science, Cochrane Library, Emcare, Academic Search Premier and Google Scholar from inception to 9 October 2025, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Eligible studies included all study designs reporting outcomes of patients with KD treated with ANK. Thirty-two publications (31 identified through database search and one by cross-referencing) describing 81 patients were included. Most reports were single cases or small series, with two early-phase clinical trials. Treatment with ANK was associated with resolution of fever and systemic inflammation in 94.9% of patients. Complete CAA resolution was reported in 32% and stabilisation/dimensional reduction in 56.3%. No serious safety concerns were identified. However, these findings derive from heterogeneous and low-quality evidence and should be interpreted with caution. In IVIG-resistant KD, ANK was effective in controlling systemic inflammation, although more data are needed to assess its efficacy on coronary outcomes. While these findings are encouraging in supporting consideration of ANK for refractory KD, larger randomised clinical studies are warranted to define optimal ANK timing of introduction and dosing, and to evaluate its long-term efficacy on cardiac outcomes. CRD420252129435.
2026-07-28 | The Autophagy-Inflammasome Axis as a Molecular Switch: From Persistent Inflammation to Vascular Remodeling in IVIG-Resistant Kawasaki Disease.
Intravenous immunoglobulin (IVIG) resistance occurs in 10-20% of children with Kawasaki disease (KD) and is associated with a 3- to 5-fold higher risk of coronary artery lesions (CALs). Yet the mechanistic basis for why some patients progress from reversible inflammation to irreversible vascular damage after IVIG remains poorly understood. Most existing reviews have focused on risk prediction rather than the mechanistic chain linking resistance to CALs. Here, we synthesize current evidence across three interconnected pathways. First, autophagy dysfunction-particularly impaired mitophagy-sustains inflammation through cGAS-STING activation. Second, neutrophil extracellular traps (NETs) play a controversial role in KD vasculitis, with PAD2 and PAD4 possibly acting redundantly via the NLRP3 inflammasome. Third, endothelial-to-mesenchymal transition (EndMT), driven by the IL-1β/TNF axis and the USP7-TGFβ2/SMAD pathway, emerges as a core event in vascular remodeling. Building on these findings, we propose the "autophagy-inflammasome axis" as a candidate molecular switch that dictates whether inflammation resolves or persists. This hypothesis is actionable: it generates three explicit, testable predictions linking autophagic integrity to inflammatory outcomes and therapeutic response. Direct experimental validation in IVIG-resistant KD models and patient samples is now urgently needed. This review provides a systematic framework for understanding how IVIG resistance transitions to irreversible CALs. It also identifies candidate biomarkers (e.g., S100A12, mtDNA, and MCM8) and therapeutic targets (autophagy inducers, NLRP3 inhibitors, USP7 inhibitors, and anakinra) that could enable earlier intervention.
2026-05-31 | Vasculitis-associated aberrant apolipoprotein A2 = VAP2 and SDF-1α in Kawasaki disease patients with coronary artery lesion.
Kawasaki disease (KD) is an acute systemic vasculitis that predominantly affects the coronary arteries. The most serious complications are coronary artery lesions (CALs), including arterial dilatation, aneurysm, and stenosis, which occur in approximately 25% of untreated patients. Intravenous immunoglobulin (IVIG) therapy markedly reduces the incidence of CALs to 2-3%; however, the underlying mechanisms of IVIG's therapeutic effects remain unclear. Recently, we identified a recombinant single-chain fragment of the variable region of human immunoglobulin G, termed VasSF, which significantly ameliorated vasculitis in SCG/Kj mice. The VasSF-binding protein of 24 kDa (VAP2) was subsequently identified as an aberrant form of apolipoprotein A2 (ApoA2) in the serum of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. We investigated whether VAP2 and related ApoA2-derived molecules are associated with CAL formation in patients with KD. Baseline demographic and clinical characteristics were evaluated in 34 patients with KD during the acute and convalescent phases. Among them, 14 (41.2%) were initial IVIG non-responders, and 10 (29.4%) developed CALs. Western blot analysis revealed that VAP2 and VasSF bound to 17-kDa serum molecules predominantly during the acute phase of KD. Notably, in the CAL group, VAP2 levels exhibited a significant correlation with stromal cell-derived factor-1α (SDF-1α) (r2 = 0.5700, p = 0.049) among 78 cytokines analyzed. VAP2 was identified as a target molecule of VasSF in association with SDF-1α in our study. Considering that VasSF has been proposed as a therapeutic candidate for ANCA-associated vasculitis through targeting of aberrant ApoA2, VasSF may likewise represent a potential therapeutic agent for KD.
2026-05-22 | Kawasaki disease complicated by macrophage activation syndrome treated with canakinumab.
An infant presented with macrophage activation syndrome as part of Kawasaki disease, and was first treated with canakinumab, followed by methylprednisolone and IVIG. Despite early treatment, giant coronary artery aneurysms developed transiently, questioning the singular role of IL-1 in KD.
antibodies
2026-09-10 | Treatment and Outcomes of Kawasaki Disease Over 40 Years.
Kawasaki disease (KD) is the leading cause of acquired heart disease in children in developed countries. Long-term prognosis depends on coronary sequelae, yet Western longitudinal data integrating acute-phase features, treatment, and long-term coronary outcomes remain limited. We conducted a longitudinal observational cohort study including consecutive children diagnosed with KD between 1982 and 2025 at a single tertiary pediatric referral center in Italy. All patients underwent clinical and echocardiographic assessment during the acute phase, followed by longitudinal annual follow-up. Coronary involvement (dilation or aneurysm) was assessed by echocardiography. Among 533 children (median age, 26 months; 59.8% male), 117 (22.0%) developed acute coronary involvement, including 27 aneurysms and 90 dilation. Intravenous immunoglobulin (IVIG) use increased from 53.3% in the 1980s to 99% after 2020. The highest rates of IVIG resistance (30.0%) and coronary lesions (27.2%) occurred between 2011 and 2020, followed by a decline in 2021-2025. Persistent coronary abnormalities were observed exclusively in patients with medium-giant aneurysms. Independent predictors of aneurysm were age less than 6 months (odds ratio [OR], 7.64), IVIG resistance (OR, 9.89), IVIG administration after day 10 (OR, 5.27), and pericardial effusion (OR, 3.16). No persistent coronary sequelae were observed in high-risk patients treated with interleukin-1 inhibitors. In this 40-year Italian cohort, coronary aneurysms were uncommon but exclusively determined long-term coronary sequelae. Younger age, delayed treatment or IVIG resistance, and pericardial effusion independently predicted aneurysm formation, highlighting major and potentially modifiable gaps in care delivery. These findings support specialist, risk-based management with prompt escalation to reduce long-term coronary morbidity.
2026-09-04 | Incomplete Kawasaki Disease Versus Non-severe Multisystem Inflammatory Syndrome in Children: Distinguishing Features from Contemporaneous Patients.
Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) share overlapping clinical features, making diagnosis challenging. We compared patients with incomplete KD to those with non-severe MIS-C to identify distinguishing characteristics. Patients were enrolled in the International KD Registry (01/2020-10/2023) from 40 centers across eight countries. Among 2146 MIS-C patients, 769 met criteria for non-severe confirmed MIS-C (no shock or ICU admission). Among 1358 KD patients, 146 met American Heart Association (AHA) criteria for confirmed incomplete KD and 372 were classified as unconfirmed incomplete KD. Demographics, clinical and laboratory features, treatment, and cardiac outcomes were compared. Non-severe MIS-C patients were significantly older (median 7.4 years) than both confirmed (2.3 years) and unconfirmed (2.5 years; p < 0.001) incomplete KD patients, and had different ethnic distributions with more Black and fewer East or South Asian patients. MIS-C patients had shorter fever duration, fewer classic KD features, and more gastrointestinal and respiratory symptoms. They demonstrated lower white blood cell counts but higher inflammatory markers and markers of organ dysfunction. Cardiac involvement differed: MIS-C patients had more myocardial dysfunction, including lower ejection fraction and higher cardiac biomarkers. Coronary artery involvement in MIS-C (median maximum z-score 1.3) was similar to unconfirmed incomplete KD (median z-score 1.3) but less than confirmed incomplete KD (median z-score 2.0; p < 0.01). Older age, distinct ethnicity, prominent gastrointestinal and respiratory symptoms, and multisystem inflammation with ventricular dysfunction but relatively less coronary artery involvement help distinguish non-severe MIS-C from incomplete KD.
2026-08-28 | Construction and subgroup validation of a predictive model for IVIG-resistance in kawasaki disease.
Kawasaki disease is an acute immune vasculitis, and intravenous immunoglobulin (IVIG) therapy was an important treatment method, although a small proportion of children exhibited IVIG resistance. Our study aimed to construct a risk model for Kawasaki disease with IVIG resistance and to validate it across different clinical characteristic subgroups, with the goal of optimizing personalized and precise management to improve patient outcomes. We first compared various factors between the groups with and without IVIG resistance. Then, we used LASSO analysis to screen for factors that significantly predicted outcomes. The selected factors were used to develop the risk model. We evaluated the model using ROC curves, calibration curves, and decision curve analysis, and conducted internal validation through 5-fold cross-validation. Finally, we performed subgroup analyses based on age, sex, and other factors. Through univariate analysis, LASSO analysis, and correlation analysis, we identified WBC, PLT, CRP, fever days, PLR, and ALT as key factors in constructing the risk model. The model achieved an area under the curve of 0.816 (95% CI: 0.775-0.857). Additionally, calibration curves, DCA, and 5-fold cross-validation demonstrated that the model had good predictive performance. The model's effectiveness was also satisfactory across various subgroups. Our study successfully constructed a risk model for Kawasaki disease with IVIG resistance in the Chinese population. The model demonstrated strong predictive ability and was validated across multiple subgroups, showing potential clinical application value.
2026-08-03 | Risk factors and long-term follow-up in acute Kawasaki disease patients with medium or large coronary artery aneurysms.
Kawasaki disease (KD) is a systemic vasculitis that affects children under the age of five. Comprehensive data on KD patients with medium or large CAA are limited. This study aims to investigate the risk factors and long-term follow-up of KD patients with medium or large CAA in a Chinese cohort. We performed a cohort study of 220 KD patients including 55 patients associated with medium or large CAA and 165 patients without coronary artery abnormality between January 2015 and April 2020. Univariate and multivariate logistic regression analyses were used to identify risk factors. All enrolled patients were followed up for more than 12 months. Days to initial IVIG treatment, IVIG resistance, albumin level and platelet count were independent risk factors for KD patients with medium or large CAA based on multivariate logistic regression analysis. At a mean follow-up duration of 49 months, CAA subgroup analysis showed that 19 medium CAA cases (54.3%) promisingly regressed to normal coronary artery diameter, with the constituent ratios of small, medium, and large CAA being 31.4%, 8.6%, and 5.7%, respectively. In contrast, none of large CAA subgroup returned to normal coronary arteries. The constituent ratio of small, medium and large CAA was 15.0%, 25.0% and 60.0%. Besides, we found that coronary thrombosis occurred in 11 acute-phase cases (20.0%; 2 in the medium CAA, 9 in the large CAA), which increased to 18 cases (32.7%; 5 in the medium CAA, 13 in the large CAA) at the end of follow-up. Days to initial IVIG treatment, IVIG resistance, albumin levels and platelet count were risk factors for KD patients with medium or large CAA. The prognosis of medium or large CAA is not ideal during a long-term follow-up, particularly for large CAA.
2026-07-28 | Pre-IVIG echocardiography enables targeted treatment in infants younger than 6 months with Kawasaki Disease : Echocardiography-based risk stratification in young infants with Kawasaki Disease.
The 2024 American Heart Association scientific statement suggests intensification therapy in infants younger than 6 months (< 6 months) with Kawasaki disease (KD) may be beneficial, but indications remain undefined. We hypothesized that pre-IVIG echocardiographic findings could identify infants < 6 months who do not require intensification beyond standard intravenous immunoglobulin (IVIG). This multicenter cohort study in Taiwan (2019-2023) included children with KD who underwent echocardiography before IVIG and received IVIG within 10 days of illness onset. Children receiving early intensification therapy were excluded. Participants were stratified as < 6 months or ≥ 6 months. Echocardiography was performed at four time points: pre-IVIG, days 11-42, weeks 7-8, and 3 months after KD onset. Among 398 children with KD, 44 (11.1%) were younger than 6 months. Infants < 6 months had higher coronary artery aneurysm (CAA) prevalence at diagnosis than older children (52.3% vs 28.5%; OR, 2.74 [95% CI, 1.45-5.18]; P = .001). IVIG within 7 days was associated with lower CAA risk in both groups. Among children with initially normal coronary dimensions, new CAA risk did not differ significantly between younger and older groups (4.8% vs 2.4%; P = .42). Among 21 infants < 6 months without initial CAA, none developed new CAA except one with KD shock syndrome. Pre-IVIG echocardiography may help identify infants < 6 months at low risk for subsequent CAA development with standard IVIG treatment. Given the observational nature of this study, larger prospective studies are warranted to confirm these findings. • Infants younger than 6 months with Kawasaki disease (KD) have elevated coronary artery aneurysm (CAA) risk. • The 2024 AHA scientific statement suggests intensification therapy may be beneficial in this age group, but clear indications remain undefined. • In infants younger than 6 months with KD and normal pre-IVIG coonary dimensions, new coronary artery aneurysms rarely developed during follow-up. • Pre-IVIG echocardiography may help identify infants <6 months at low risks for subsequent CAA development with standard IVIG treatment.
oligonucleotides
2026-06-17 | [Effect of miR-155-5p regulating the TLR4/MAPK/NF-κB pathway on inflammatory response, coronary artery lesion and immune function in mice with Kawasaki disease].
To investigate the effect of miR-155-5p regulation of the TLR4/MAPK/NF-κB pathway on inflammatory response, coronary artery lesion, and immune function in mice with Kawasaki disease (KD). Sixty male BALB/C mice were randomly assigned to six groups (n=10 each): healthy, KD, miR-155-5p agomir, agomir-negative control (agomir-NC), miR-155-5p antagomir, and antagomir-negative control (antagomir-NC). KD models were established by intraperitoneal injection of Lactobacillus casei cell wall extract in all groups except the healthy group. Levels of interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α were measured by ELISA. Flow cytometry was used to determine the proportions of CD3+, CD4+, and CD8+ T lymphocyte subsets and the CD4+/CD8+ ratio. Coronary artery diameter was assessed by high-frequency ultrasound, and histopathological changes were observed by hematoxylin-eosin staining. Endothelial cell apoptosis in coronary tissue was detected with TUNEL staining. Expression levels of nuclear factor kappa-B (NF-κB) p65, phosphorylated NF-κB p65 (p-NF-κB p65), Toll-like receptor 4 (TLR4), and p38 mitogen-activated protein kinase (MAPK) proteins were analyzed by Western blot. Compared with the healthy group, the KD group showed coronary arterial wall thickening, endothelial shedding, extensive inflammatory cell infiltration, disordered smooth muscle layer arrangement, vascular dilation, and lumen stenosis. The miR-155-5p agomir group exhibited aggravated coronary inflammation, wall thickening, and lumen stenosis versus the KD group, whereas the miR-155-5p antagomir group showed attenuated inflammation and wall thickening, improved smooth muscle arrangement, and reduced stenosis. The KD group demonstrated increased IL-6, IL-1β, TNF-α, CD4+ T cell percentage, CD4+/CD8+ ratio, coronary artery diameter, endothelial apoptosis rate, and p-NF-κB p65, TLR4, and p38 MAPK protein expression compared to the healthy group (all P<0.05), with decreased CD3+ and CD8+ T cell percentages (P<0.05). No significant differences were observed among the KD, agomir-NC, and antagomir-NC groups. Compared with the KD group, the miR-155-5p agomir group showed further increased inflammatory cytokines (IL-6, IL-1β, and TNF-α), CD4+ T cell percentage, CD4+/CD8+ ratio, coronary diameter, endothelial apoptosis, and protein expression of p-NF-κB p65, TLR4, and p38 MAPK, while reduced CD3+ and CD8+ T cell percentages (all P<0.05). Conversely, the miR-155-5p antagomir group showed significant reductions in inflammatory cytokines, protein expression of p-NF-κB p65, TLR4, and p38 MAPK, CD4+ T cell percentage, CD4+/CD8+ ratio, coronary artery diameter, and endothelial apoptosis, as well as significant increases in CD3+ and CD8+ T cell percentages (all P<0.05). Overexpression of miR-155-5p exacerbates inflammatory response, coronary artery lesions, endothelial cell apoptosis, and immune dysfunction in KD, potentially through modulation of the TLR4/MAPK/NF-κB pathway. Inhibition of miR-155-5p may reverse these pathological changes.
2024-08-21 | LncRNAs in Kawasaki disease and Henoch-Schönlein purpura: mechanisms and clinical applications.
Kawasaki disease (KD) and Henoch-Schönlein purpura (HSP) are the two most predominant types of childhood vasculitis. In childhood vasculitis, factors such as lack of sensitive diagnostic indicators and adverse effects of drug therapy may cause multiorgan system involvement and complications and even death. Many studies suggest that long noncoding RNAs (lncRNAs) are involved in the mechanism of vasculitis development in children and can be used to diagnose or predict prognosis by lncRNAs. In existing drug therapies, lncRNAs are also involved in drug-mediated treatment mechanisms and are expected to improve drug toxicity. The aim of this review is to summarize the link between lncRNAs and the pathogenesis of KD and HSP. In addition, we review the potential applications of lncRNAs in multiple dimensions, such as diagnosis, treatment, and prognosis prediction. This review highlights that targeting lncRNAs may be a novel therapeutic strategy to improve and treat KD and HSP.
2023-11-08 | NFIL3 aggravates human coronary artery endothelial cell injury by promoting ITGAM transcription in Kawasaki disease.
High expression of nuclear factor interleukin-3 (NFIL3) and integrin Alpha M (ITGAM) was found in serum samples from Kawasaki disease (KD) patients through bioinformatics analysis. Hence, this study aimed to explore the biological functions of NFIL3 and ITGAM in KD serum-stimulated human coronary artery endothelial cells (HCAECs). The differentially-expressed genes in KD were analyzed through bioinformatics analysis. Serum samples were obtained from 18 KD patients and 18 healthy volunteers, followed by detection of NFIL3 and ITGAM levels in KD serum. After HCAECs were transfected with sh-NFIL3, sh-ITGAM, or sh-NFIL3 + oe-ITGAM and underwent 24-h KD serum stimulation, cell viability and apoptosis and the levels of inflammation-related factors were measured. The binding between NFIL3 and ITGAM was validated by dual-luciferase and chromatin immunoprecipitation (ChIP) assays. NFIL3 and ITGAM were up-regulated in serum from KD patients and KD serum-stimulated HCAECs. Down-regulation of NFIL3 or ITGAM inhibited KD serum-induced cell apoptosis and inflammatory response of HCAECs and promoted cell viability. Mechanistically, NFIL3 promoted ITGAM transcription level. Up-regulation of ITGAM reversed the improvement of NFIL3 down-regulation on KD serum-induced HCAEC injury. NFIL3 aggravated KD serum-induced HCAEC injury by promoting ITGAM transcription, which provided new insights into the treatment of KD.
2023-07-31 | MiR-223-3p affects the proliferation and apoptosis of HCAECs in Kawasaki disease by regulating the expression of FOXP3.
Kawasaki disease (KD) can lead to permanent damage to coronary structures, the pathogenesis of which remains unknown. This experiment was designed to investigate whether miR-223-3p secreted in the serum of KD patients affects the proliferation and apoptosis of HCAECs in KD by regulating FOXP3. Blood samples were collected in acute febrile phase of KD, after IVIG treatment, and from healthy controls. Transfected into HCAECs cells by synthetic FOXP3 siRNA/NC. A co-culture system was established between HCAECs cells transfected with FOXP3 siRNA/NC and THP1 cells added with three sera. Compared with the control group, the expressions of miR-223-3p, RORγt, and Th17 in serum of KD patients were significantly upregulated, and the expressions of TGF-β1, FOXP3 and Treg were significantly downregulated. At the same time, the levels of IL-6, IL-17, and IL-23 were significantly increased, and the levels of IL-10 and FOXP3 were significantly decreased. After IVIG treatment, the patient's above results were reversed. The serum of KD patients increased the expression of miR-223-3p and inhibited the expression of FOXP3 in HCAECs cells. IVIG serum is the opposite. Overexpression of miR-223-3p also promoted the apoptosis of HCAECs. In addition, serum from KD patients promoted apoptosis, whereas serum after IVIG treatment inhibited apoptosis. KD patient serum downregulated the expression of FOXP3, Bcl2, TGF-β1 and IL-10 in cells, and upregulated the expression of caspase3, Bax, IL-17, IL-6, and IL-23. The opposite results were obtained with IVIG-treated sera. miR-223-3p secreted in serum of KD patients can regulate the expression of FOXP3 and affect the proliferation, apoptosis, and inflammation of cells.
2023-07-19 | CircRNA7632 down-regulation alleviates endothelial cell dysfunction in Kawasaki disease via regulating IL-33 expression.
Kawasaki disease (KD) is a form of idiopathic vasculitis frequently accompanied by coronary artery lesions, which involves endothelial dysfunction. Recent studies have demonstrated that circular RNAs (circRNAs) are implicated in many cardiovascular diseases. However, few studies have examined the role of circRNAs on endothelial dysfunction in KD. In this study, we investigated the role of circ7632 on endothelial-mesenchymal transition (EndoMT) in KD and then explored the underlying mechanism. Children diagnosed with KD and age-matched healthy controls (HC) were included. Sera samples were collected. Primary human umbilical vein endothelial cells (HUVECs) were obtained and incubated with 15% HC and KD serum for 48 h. The mRNA and protein expression of mesenchymal markers vimentin and α-smooth muscle actin (α-SMA) and endothelial marker zonula occludens-1 (ZO-1) in HUVECs transfected with plasmid-circ7632 and si-circ7632 were detected by RT-qPCR and Western blot analysis. CCK8, scratch test, and migration test were performed to examine the effect of circ7632 on the cell proliferation and migration. The circ7632 level was higher in HUVECs treated by KD serum than in HUVECs treated with HC serum. Overexpression of circ7632 significantly increased vimentin and α-SMA expression, decreased ZO-1 expression, and also decreased cell proliferation. Down-regulation of circ7632 expression got the opposite results. RNA-seq analysis, and confirmatory experiment displayed that down-regulation of circ7632 decreased IL-33 expression, and IL-33 silencing mitigated KD serum-mediated EndoMT. Our study revealed that circ7632 level was elevated in KD serum-treated HUVECs. Circ7632 down-regulation could alleviate EndoMT likely through decreasing IL-33 expression. The circ7632 may become a potential therapeutic target for KD.
other
2026-04-24 | Overview of T-cell subsets and related cytokines in Kawasaki disease.
Kawasaki disease (KD) is an acute febrile inflammatory illness in children characterized by systemic vasculitis; the etiology and pathogenesis have not been fully clarified. In recent years, studies have shown that T cell-mediated immune abnormalities play an important role in the development of KD. This paper reviewed the dynamic changes of T cell subsets (e.g., Th1, Th17, Treg, etc.) and their regulatory mechanisms in KD, focusing on the molecular mechanisms of T cell-mediated cytokine storm, autoimmune response and vascular injury. In addition, this paper summarizes the research progress of T cell-targeted therapy in KD, which provides a new theoretical basis for the optimization of clinical intervention strategies. By systematically combing the roles and mechanisms of T cells in KD, aims to provide reference for further elucidation of its pathogenesis and development of novel therapeutic approaches. IMPACT: T cells exhibit different immune responses in physiological and pathological states. Different T cell subsets are functionally diverse. Different T cell subsets in patients with Kawasaki disease exhibit significant differences in activity that correlate with therapeutic efficacy. Studies of T cell subsets reveal potential immunotherapeutic targets and improve our understanding of Kawasaki disease.
2025-11-21 | Therapeutic Plasma Exchange Resolves Inflammation With Increased HSD11B1 in Kawasaki Disease.
Kawasaki disease (KD) is an acute inflammatory disorder in children. The important complication of coronary artery aneurysms occurs in treatment-resistant patients. Therapeutic plasma exchange (TPE) has been effective for some refractory KD. Here, we investigated the effectiveness of TPE and how the glucocorticoid amplifying enzyme, 11beta-hydroxysteroid dehydrogenase 1, is involved in the resolution of inflammation in refractory KD.
2025-07-08 | The Caveolin-1/nuclear factor kappa-B signalling pathway is involved in Kawasaki disease vasculitis induced by Lactobacillus casei cell wall extract.
Kawasaki disease (KD) is an acute vasculitis and its pathogenesis is complex. Caveolin-1 (Cav-1) is the main structural protein of caveolae and is involved in the pathogenesis of many vascular diseases. A clinical study revealed that the Cav-1 serum level in children significantly increases in the acute phase of KD, but the role of Cav-1 in KD is still unclear. We aimed to explore whether and how Cav-1 is involved in the KD pathogenesis. KD vasculitis was induced by Lactobacillus casei cell wall extract intraperitoneal injection in mice, and Cav-1 expression was inhibited by adeno-associated viruses (AAV)-Cav-1 shRNA. Cardiovascular lesions was assessed via haematoxylin and eosin staining. Proinflammatory cytokine and matrix metalloproteinase-9 levels were measured via quantitative real-time polymerase chain reaction. Endothelial cell adhesion molecule expression was evaluated by immunohistochemistry. Cav-1 expression and nuclear factor kappa-B pathway activation were evaluated by Western blotting. Mice with Lactobacillus casei cell wall extract-induced KD vasculitis exhibited severe heart vessel inflammation and increased Cav-1, proinflammatory cytokine, matrix metalloproteinase-9, and endothelial cell adhesion molecule expression, which were reversed after Cav-1 inhibition. Moreover, nuclear factor kappa-B activation of KD vasculitis model mice was suppressed after Cav-1 inhibition. Cav-1 participates in KD vasculitis pathogenesis by regulating the nuclear factor kappa-B signalling pathway.
2025-07-01 | Vaccine-associated Kawasaki disease in children
Kawasaki disease (KD) is a leading cause of heart disease in children. The etiology of KD is currently unknown. The onset of KD occurs with delays following pathogen outbreaks and also post-immunization. A recent etiology model of KD proposed that KD is caused by activation of mast cells and likely platelets. Recently, it was discovered that epilepsy safety signals were associated with specific vaccines for infants aged 0 and 1. The problem statement of this paper is whether these safety signals also appear in children post-immunization. Herein, the Vaccine Adverse Event Reporting System was retrospectively examined for KD adverse events (AEs) for children. The same pattern of safety signals was observed with KD AEs as epilepsy AEs post-immunization. KD associated with vaccination (KD-V) is associated with either a pattern consistent with direct innate immune activation or immune complex activation of mast cells and likely platelets. Candidate causative factors identified include live virus vaccines and very high dosage levels for specific infant vaccines and specific concomitant combinations. Adjusting vaccine dosage based on infant body size for several vaccines is strongly recommended, including adjusting the infectious units in attenuated live viral vaccines. Concomitant administration of specific vaccines results in either additive or synergy risk levels for KD. Concomitant administration of specific vaccines, including attenuated live viruses with synergy KD risk levels, is strongly recommended against (counterindicated).
2025-06-01 | Clinical Outcomes of Using Radial Artery for Coronary Artery Bypass Graft in Children With Kawasaki Disease.
To investigate the early clinical outcomes of using radial artery (RA) graft for coronary artery bypass graft (CABG) surgery in children with coronary sequelae of Kawasaki disease (KD). Clinical data of all 26 children (22 male, 4 female) with coronary sequelae of KD who underwent CABG with RA graft at our hospital between March 2016 and September 2023 were retrospectively analyzed. The severity of coronary artery lesions was classified as Va or Vb in all patients. The median (P25, P75) age of patients was 8.5 (6.0, 11.3) y and the median weight was 33.0 (21.0, 45.3) kg. The mean interval from diagnosis to operation was 5.4 ± 3.7 y. The median postoperative mechanical ventilation time was 6.0 (4.0, 12.3) h. The median intensive care unit stay was 2.0 (2.0, 3.3) d. The median length of postoperative hospital stay was 19.0 (13.0, 29.0) d. Postoperative follow-up time ranged from 0.2 to 5.8 y, and no cardiovascular-related complications occurred. Sixteen patients underwent cardiac catheterization or CT angiography during follow-up. One patient each had anastomotic stenosis in RA and right internal thoracic artery graft, respectively, while myocardial perfusion imaging showed no worsening of myocardial ischemia. There was no significant difference in forearm motor and sensory function between the operated and the contralateral arm; brachial artery angiography showed well-established forearm collateral vessels. CABG is a safe and effective treatment for KD with severe coronary lesions in children. The RA graft has good early patency without impairing forearm function. Individualized surgical and anticoagulant strategies may help improve the prognosis.
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Drug Discovery Landscape
5 orphan drug designations for Kawasaki disease.
5 orphan drug designations for Kawasaki disease.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
Infliximab | antibodies | EMA | Oddifact | |
acetylsalicylic acid | small molecules | FDA | Academic Pharmaceuticals Inc. | |
infliximab | antibodies | FDA | ODDIFACT SAS | |
aspirin for injection (acetylsalicylic acid) | small molecules | FDA | Rhoshan Pharmaceuticals Inc. | |
Ulinastatin | small molecules | FDA | — | RNR BioMedical Inc. |
“Terminated” – programs with discontinued clinical trials, or with no updates reported for 5 years after completion or 12 years after the last trial started.
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