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
1,912 drug discovery papers about Kawasaki disease, with 4 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,912 drug discovery papers about Kawasaki disease, with 4 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-13 | Biochemical outcomes and safety profiles of compound glycyrrhizin versus magnesium isoglycyrrhizinate in Kawasaki disease: a retrospective propensity score‑matched cohort study.
Hepatic dysfunction is a common extra-cardiac manifestation of Kawasaki disease (KD). Compound glycyrrhizin (CG) and magnesium isoglycyrrhizinate (MgIG) are widely used hepatoprotective agents in Asian populations. However, no study has directly compared their efficacy and safety in pediatric KD patients with liver enzyme abnormalities. This study aims to compare the biochemical outcomes and safety profiles of CG versus MgIG in KD children with elevated liver enzymes, and to identify factors associated with treatment response. This retrospective cohort study included KD inpatients with alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels >2 times the upper limit of normal (ULN) who received monotherapy with either CG or MgIG. Propensity score matching (PSM) at a 2:1 ratio was applied to balance baseline characteristics. Biochemical responses were assessed by the absolute changes in ALT and AST from baseline to 1 week, as well as by categorical responses (complete normalization and partial biochemical response). A multivariable logistic regression model was used to evaluate the independent association between treatment group and partial biochemical response, adjusting for gender, timing of treatment initiation, and intravenous immunoglobulin (IVIG) resistance. Safety profiles were also compared. After PSM, 129 patients (CG: n=80; MgIG: n=49) were analyzed. Both treatments were associated with significant reductions in ALT and AST from baseline (all P<0.001), with no significant between‑group differences in absolute changes (ALT: P=0.07; AST: P=0.11). Partial biochemical response at 1 week was observed in 86.25% of CG patients and 69.39% of MgIG patients (P=0.02). However, after adjusting for gender, timing of treatment initiation, and IVIG resistance, treatment group was not independently associated with partial biochemical response [odds ratio (OR) =0.542, 95% confidence interval (CI): 0.203-1.452, P=0.22]. Each 1‑day delay in treatment initiation was associated with a 19% reduction in the odds of response, making it the only significant independent predictor. Adverse events were reported in 3.75% of CG patients and 4.08% of MgIG patients, with no serious events and no significant between‑group difference (P>0.99). In this retrospective PSM cohort study, both CG and MgIG were associated with significant biochemical improvements from baseline. After adjustment for confounders, no independent association was found between treatment group and partial biochemical response. Earlier initiation of hepatoprotective therapy was the only factor significantly associated with better biochemical outcomes.
2026-08-12 | Bioinformatics identification of mitochondrial dynamics-related potential biomarkers in kawasaki disease and prediction of potential regulatory correlations.
Kawasaki disease (KD) is a systemic vasculitis. Mitochondria was found to promote the activation of NLRP3 inflammatory vesicles, which have been shown to be a key driver of vascular disease. And there are few relevant reports of mitochondrial dynamic (MD) in KD. This study aimed to distinguish the potential biomarkers related to MD in KD and supply ideas for the intervention and treatment of KD. Currently, functional experimental verification in this field is lacking, and this study preliminarily explores their potential correlations through bioinformatics analysis. Differential expression analysis, machine learning, and expression validation were employed to identify potential biomarkers. Subsequently, analyses like enrichment analysis, immune infiltration analysis, and molecular regulatory network were applied to probe the underlying mechanisms of potential biomarkers. RAP2C, DPM2, and DDX59 were identified as potential biomarkers associated with MD in KD and were mainly involved in inflammation-related pathways. Notably, 13 differential immune cells were gained in KD and control groups, 9 of which showed strong correlation with potential biomarkers, suggesting a relationship between potential biomarkers and the immune microenvironment in KD. For example, DPM2 had the positive relationship with CD8 T cells, while DDX59 had the negative relationship with CD8 T cells. Afterwards, molecular regulatory networks of potential biomarkers were constructed, specifically, they shared 5 common microRNAs (miRNAs) and 3 common transcription factors (TFs). Ultimately, potential biomarkers had 3 common targeting drugs [valproic acid, benzo(a)pyrene, and acetaminophen]; notably, benzo(a)pyrene was excluded due to carcinogenicity, which supplied the basis for targeting potential biomarkers to treat KD. The potential biomarkers (RAP2C, DPM2, and DDX59) related to MD in KD were acquired. These findings provide preliminary insights for future drug repurposing studies targeting KD and offer bioinformatic evidence for a potential link between mitochondrial dynamics and the immune microenvironment in KD.
2026-08-12 | Ruxolitinib combined with corticosteroids for the successful treatment of kawasaki disease-associated macrophage activation syndrome: a case report.
To explore the diagnostic challenges of Kawasaki disease (KD)-associated macrophage activation syndrome (MAS) and the therapeutic value of ruxolitinib combined with corticosteroids. We retrospectively analyzed the clinical data of one pediatric patient with KD-associated MAS and conducted sorting and analysis of relevant published literature. A 14-month-old male infant presented with fever and rash and was diagnosed with severe KD. Despite initial treatment with intravenous immunoglobulin (IVIG) and aspirin, he developed persistent fever, progressive cytopenia, hepatosplenomegaly, hypofibrinogenemia, hyperferritinemia, reduced NK-cell activity, and extremely elevated soluble interleukin-2 receptor (sCD25), fulfilling the HLH-2004 criteria for MAS. He was successfully treated with ruxolitinib plus methylprednisolone, with rapid resolution of fever, recovery of blood counts, and improvement in coagulation and inflammatory markers. KD-associated MAS is rare but life-threatening. Early recognition of warning signs and prompt initiation of ruxolitinib-based combination therapy can effectively control cytokine storm and improve clinical outcomes.
2026-08-06 | Implications of isonicotinylation-associated patterns in NK cells in the pathogenesis of Kawasaki disease: evidence from artificial intelligence-driven multi-omics and clinical validation.
Kawasaki disease (KD) is a systemic vasculitis of childhood driven by aberrant immune activation. Natural killer (NK) cell dysregulation plays a critical role, but its upstream molecular mechanisms remain unclear. Isonicotinylation (Kinic), a novel lysine acylation acting as a metabolic sensor, represents an unexplored regulatory layer in KD. We employed an artificial intelligence (AI)-driven multi-omics framework. Limma differential expression analysis on GSE68004 (KD patient bulk profile) identified Kinic-related differentially expressed genes. Weighted gene co-expression network analysis (WGCNA) and CIBERSORT on GSE18606 (KD patient bulk profile) delineated an NK cell-correlated module. Their intersection defined Kinic- and NK (KN)-related signature, which was used to construct a diagnostic model via an explainable machine learning pipeline on KD patient bulk profiles (GSE73463, GSE73462, and GSE63881). The central hub gene was validated using KD patient single-cell RNA-sequencing (scRNA-seq) data (GSE24757). An AI-based drug screen (DrugReflector) and molecular docking nominated therapeutic candidates. Finally, PPID expression was validated in an independent clinical cohort using q-RT-PCR. We identified a six-gene KN-associated signature that demonstrated excellent diagnostic performance. PPID can be considered upregulated hub gene. Single-cell analysis confirmed predominant PPID expression in NK cells and linked its function to epigenetic modification and inflammatory signaling. Drug screening nominated BRD-K90382497 as a potential PPID-targeting compound. This study unveils a novel KN-associated molecular axis in KD pathogenesis, with PPID as an NK cell-centric hub. This axis provides a promising diagnostic biomarker and identifies a potential therapeutic target, bridging a novel metabolic modification to NK cell dysfunction in KD.
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.
2026-08-13 | Biochemical outcomes and safety profiles of compound glycyrrhizin versus magnesium isoglycyrrhizinate in Kawasaki disease: a retrospective propensity score‑matched cohort study.
Hepatic dysfunction is a common extra-cardiac manifestation of Kawasaki disease (KD). Compound glycyrrhizin (CG) and magnesium isoglycyrrhizinate (MgIG) are widely used hepatoprotective agents in Asian populations. However, no study has directly compared their efficacy and safety in pediatric KD patients with liver enzyme abnormalities. This study aims to compare the biochemical outcomes and safety profiles of CG versus MgIG in KD children with elevated liver enzymes, and to identify factors associated with treatment response. This retrospective cohort study included KD inpatients with alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels >2 times the upper limit of normal (ULN) who received monotherapy with either CG or MgIG. Propensity score matching (PSM) at a 2:1 ratio was applied to balance baseline characteristics. Biochemical responses were assessed by the absolute changes in ALT and AST from baseline to 1 week, as well as by categorical responses (complete normalization and partial biochemical response). A multivariable logistic regression model was used to evaluate the independent association between treatment group and partial biochemical response, adjusting for gender, timing of treatment initiation, and intravenous immunoglobulin (IVIG) resistance. Safety profiles were also compared. After PSM, 129 patients (CG: n=80; MgIG: n=49) were analyzed. Both treatments were associated with significant reductions in ALT and AST from baseline (all P<0.001), with no significant between‑group differences in absolute changes (ALT: P=0.07; AST: P=0.11). Partial biochemical response at 1 week was observed in 86.25% of CG patients and 69.39% of MgIG patients (P=0.02). However, after adjusting for gender, timing of treatment initiation, and IVIG resistance, treatment group was not independently associated with partial biochemical response [odds ratio (OR) =0.542, 95% confidence interval (CI): 0.203-1.452, P=0.22]. Each 1‑day delay in treatment initiation was associated with a 19% reduction in the odds of response, making it the only significant independent predictor. Adverse events were reported in 3.75% of CG patients and 4.08% of MgIG patients, with no serious events and no significant between‑group difference (P>0.99). In this retrospective PSM cohort study, both CG and MgIG were associated with significant biochemical improvements from baseline. After adjustment for confounders, no independent association was found between treatment group and partial biochemical response. Earlier initiation of hepatoprotective therapy was the only factor significantly associated with better biochemical outcomes.
2026-08-12 | Bioinformatics identification of mitochondrial dynamics-related potential biomarkers in kawasaki disease and prediction of potential regulatory correlations.
Kawasaki disease (KD) is a systemic vasculitis. Mitochondria was found to promote the activation of NLRP3 inflammatory vesicles, which have been shown to be a key driver of vascular disease. And there are few relevant reports of mitochondrial dynamic (MD) in KD. This study aimed to distinguish the potential biomarkers related to MD in KD and supply ideas for the intervention and treatment of KD. Currently, functional experimental verification in this field is lacking, and this study preliminarily explores their potential correlations through bioinformatics analysis. Differential expression analysis, machine learning, and expression validation were employed to identify potential biomarkers. Subsequently, analyses like enrichment analysis, immune infiltration analysis, and molecular regulatory network were applied to probe the underlying mechanisms of potential biomarkers. RAP2C, DPM2, and DDX59 were identified as potential biomarkers associated with MD in KD and were mainly involved in inflammation-related pathways. Notably, 13 differential immune cells were gained in KD and control groups, 9 of which showed strong correlation with potential biomarkers, suggesting a relationship between potential biomarkers and the immune microenvironment in KD. For example, DPM2 had the positive relationship with CD8 T cells, while DDX59 had the negative relationship with CD8 T cells. Afterwards, molecular regulatory networks of potential biomarkers were constructed, specifically, they shared 5 common microRNAs (miRNAs) and 3 common transcription factors (TFs). Ultimately, potential biomarkers had 3 common targeting drugs [valproic acid, benzo(a)pyrene, and acetaminophen]; notably, benzo(a)pyrene was excluded due to carcinogenicity, which supplied the basis for targeting potential biomarkers to treat KD. The potential biomarkers (RAP2C, DPM2, and DDX59) related to MD in KD were acquired. These findings provide preliminary insights for future drug repurposing studies targeting KD and offer bioinformatic evidence for a potential link between mitochondrial dynamics and the immune microenvironment in KD.
2026-08-12 | Ruxolitinib combined with corticosteroids for the successful treatment of kawasaki disease-associated macrophage activation syndrome: a case report.
To explore the diagnostic challenges of Kawasaki disease (KD)-associated macrophage activation syndrome (MAS) and the therapeutic value of ruxolitinib combined with corticosteroids. We retrospectively analyzed the clinical data of one pediatric patient with KD-associated MAS and conducted sorting and analysis of relevant published literature. A 14-month-old male infant presented with fever and rash and was diagnosed with severe KD. Despite initial treatment with intravenous immunoglobulin (IVIG) and aspirin, he developed persistent fever, progressive cytopenia, hepatosplenomegaly, hypofibrinogenemia, hyperferritinemia, reduced NK-cell activity, and extremely elevated soluble interleukin-2 receptor (sCD25), fulfilling the HLH-2004 criteria for MAS. He was successfully treated with ruxolitinib plus methylprednisolone, with rapid resolution of fever, recovery of blood counts, and improvement in coagulation and inflammatory markers. KD-associated MAS is rare but life-threatening. Early recognition of warning signs and prompt initiation of ruxolitinib-based combination therapy can effectively control cytokine storm and improve clinical outcomes.
2026-08-06 | Implications of isonicotinylation-associated patterns in NK cells in the pathogenesis of Kawasaki disease: evidence from artificial intelligence-driven multi-omics and clinical validation.
Kawasaki disease (KD) is a systemic vasculitis of childhood driven by aberrant immune activation. Natural killer (NK) cell dysregulation plays a critical role, but its upstream molecular mechanisms remain unclear. Isonicotinylation (Kinic), a novel lysine acylation acting as a metabolic sensor, represents an unexplored regulatory layer in KD. We employed an artificial intelligence (AI)-driven multi-omics framework. Limma differential expression analysis on GSE68004 (KD patient bulk profile) identified Kinic-related differentially expressed genes. Weighted gene co-expression network analysis (WGCNA) and CIBERSORT on GSE18606 (KD patient bulk profile) delineated an NK cell-correlated module. Their intersection defined Kinic- and NK (KN)-related signature, which was used to construct a diagnostic model via an explainable machine learning pipeline on KD patient bulk profiles (GSE73463, GSE73462, and GSE63881). The central hub gene was validated using KD patient single-cell RNA-sequencing (scRNA-seq) data (GSE24757). An AI-based drug screen (DrugReflector) and molecular docking nominated therapeutic candidates. Finally, PPID expression was validated in an independent clinical cohort using q-RT-PCR. We identified a six-gene KN-associated signature that demonstrated excellent diagnostic performance. PPID can be considered upregulated hub gene. Single-cell analysis confirmed predominant PPID expression in NK cells and linked its function to epigenetic modification and inflammatory signaling. Drug screening nominated BRD-K90382497 as a potential PPID-targeting compound. This study unveils a novel KN-associated molecular axis in KD pathogenesis, with PPID as an NK cell-centric hub. This axis provides a promising diagnostic biomarker and identifies a potential therapeutic target, bridging a novel metabolic modification to NK cell dysfunction in KD.
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.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
5 orphan drug designations for Kawasaki disease.
5 orphan drug designations for Kawasaki disease.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Infliximab | antibodies | EMA | 2026-05-20 | — | Oddifact |
acetylsalicylic acid | small molecules | FDA | 2025-12-19 | — | Academic Pharmaceuticals Inc. |
infliximab | antibodies | FDA | 2024-07-26 | — | ODDIFACT SAS |
aspirin for injection (acetylsalicylic acid) | small molecules | FDA | 2020-09-18 | — | Rhoshan Pharmaceuticals Inc. |
Ulinastatin | small molecules | FDA | 2020-06-12 | — | RNR BioMedical Inc. |
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