Kawasaki Disease is a condition in children that involves inflammation of blood vessels throughout the body and is characterized by fever, rash, and other symptoms.
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name: Kawasaki Disease
creation_date: '2025-12-04T16:57:31Z'
updated_date: '2026-04-30T12:00:00Z'
description: Kawasaki Disease is a condition in children that involves
inflammation of blood vessels throughout the body and is characterized by
fever, rash, and other symptoms.
category: Pediatric Condition
parents:
- Vasculitis
inheritance:
- name: Polygenic inheritance
inheritance_term:
preferred_term: Polygenic inheritance
term:
id: HP:0010982
label: Polygenic inheritance
description: >
Kawasaki disease has a multigenic/multifactorial inheritance pattern with
susceptibility loci identified in ITPKC, FCGR2A, BLK, CD40, CASP3, and
HLA regions.
evidence:
- reference: ORPHA:2331
supports: SUPPORT
snippet: "Multigenic/multifactorial"
explanation: Orphanet classifies the inheritance pattern of Kawasaki disease
as multigenic/multifactorial.
prevalence:
- population: Children under 5
percentage: Rare
evidence:
- reference: PMID:10392592
reference_title: "Kawasaki disease."
supports: REFUTE
snippet: Most children who contract this illness are less than two years old, and 80 percent of affected children are younger than five years of age.
explanation: The statement that Kawasaki disease is rare in children under 5 is refuted by the literature, which indicates that 80% of affected children are younger than five years of age.
- reference: PMID:36611091
reference_title: "Epidemiology and risk factors for resistance to treatment of Kawasaki disease in Cyprus."
supports: REFUTE
snippet: 83% of patients were < 5 years of age and 10% were < 6 months.
explanation: The study shows that a significant proportion of Kawasaki
disease cases occur in children under 5 years of age, refuting the
statement that it is rare in this population.
- reference: ORPHA:2331
supports: SUPPORT
snippet: "Unknown | Worldwide | Point prevalence | ORPHANET"
explanation: Orphanet classifies the worldwide point prevalence as unknown,
reflecting the variability in incidence across populations (highest in
Japan and East Asia).
progression:
- phase: Onset
age_range: 6 months to 5 years
notes: Sudden onset with high fever
evidence:
- reference: PMID:36472296
reference_title: "A CASE OF KAWASAKI DISEASE IN AN EIGHT-YEAR-OLD BOY."
supports: PARTIAL
snippet: Given the variety and inconsistency of the clinical symptoms (the child had four of the five mandatory criteria together with prolonged fever), there was a late diagnosis, namely on day 10 of the disease.
explanation: This reference mentions prolonged fever as a symptom of Kawasaki Disease but does not specify the sudden onset of high fever.
- reference: PMID:34459958
reference_title: "Kawasaki disease in children younger than 6 months of age: characteristics of a Spanish cohort."
supports: PARTIAL
snippet: A retrospective study that compared children younger than 6 months versus older children of a Spanish cohort of patients diagnosed with Kawasaki disease between 2011 and 2016 (Kawa-Race study).
explanation: This reference provides information on Kawasaki Disease in children younger than 6 months and older but does not specifically mention the age range of 6 months to 5 years or the sudden onset with high fever.
- reference: PMID:37553209
reference_title: "Rising Kawasaki disease incidence in New Zealand: analysis of national population incidence and outcomes 2000-2017."
supports: PARTIAL
snippet: The mean age was 39.8 months (SD 37) and 592 (59%) were boys.
explanation: This reference indicates that the mean age of Kawasaki Disease patients was within the 6 months to 5 years range but does not specifically mention the sudden onset with high fever.
- reference: PMID:31910632
reference_title: "Japanese Kawasaki Disease Scoring Systems: Are they Applicable to the Iranian Population?"
supports: PARTIAL
snippet: Kawasaki disease (KD) is the most frequent cause of coronary artery aneurysm (CAA) in children.
explanation: This reference focuses on coronary artery aneurysm in children with Kawasaki Disease but does not provide specific details about the age range or the sudden onset with high fever.
- reference: PMID:36611091
reference_title: "Epidemiology and risk factors for resistance to treatment of Kawasaki disease in Cyprus."
supports: PARTIAL
snippet: 83% of patients were < 5 years of age and 10% were < 6 months.
explanation: This reference mentions that 83% of Kawasaki Disease patients were under 5 years of age but does not specify the sudden onset with high fever.
- phase: Acute
duration: 1-2 weeks
notes: High fever, rash, conjunctivitis, swollen hands and feet
evidence:
- reference: PMID:9665974
reference_title: "Kawasaki syndrome."
supports: PARTIAL
snippet: The illness is manifested by prolonged fever, conjunctival injection, enanthem, exanthem, erythema and swelling of the hands and feet, and cervical adenopathy. These acute features of illness are self-limiting.
explanation: The reference confirms the symptoms mentioned in the statement (high fever, rash, conjunctivitis, swollen hands and feet) during the acute phase of Kawasaki Disease. However, it does not specify the exact duration of 1-2 weeks.
- reference: PMID:31974671
reference_title: "Clinico-laboratory profile of Kawasaki disease with arthritis in children."
supports: PARTIAL
snippet: Arthritis in KD is usually non-erosive, self-limiting, and responds well to a short course of NSAIDs.
explanation: The reference mentions that arthritis in KD is self-limiting, which implies a limited duration. However, it does not explicitly confirm the 1-2 week duration for the acute phase.
- reference: PMID:39117827
reference_title: "Kawasaki Disease-Associated Cytokine Storm Syndrome."
supports: PARTIAL
snippet: Kawasaki disease (KD) is a hyperinflammatory syndrome manifesting as an acute systemic vasculitis characterized by fever, nonsuppurative conjunctival injection, rash, oral mucositis, extremity changes, and cervical lymphadenopathy.
explanation: The reference confirms the symptoms mentioned in the statement during the acute phase of Kawasaki Disease. However, it does not specify the exact duration of 1-2 weeks.
- phase: Subacute
duration: 2-4 weeks
notes: Peeling skin, joint pain, possible coronary artery changes
evidence:
- reference: PMID:28580712
reference_title: "Kawasaki disease: State of the art."
supports: PARTIAL
snippet: Kawasaki disease begins as a necrotizing arteritis with neutrophilic infiltrate, followed by subacute/chronic changes and luminal myofibroblastic proliferation that can cause coronary artery stenosis.
explanation: This reference mentions the subacute phase and coronary artery changes but does not specify the duration of 2-4 weeks or mention peeling skin and joint pain.
- reference: PMID:33453126
reference_title: "Kawasaki disease for the paediatric dermatologist: skin manifestations and new insights into the pathophysiology."
supports: PARTIAL
snippet: All children with KD have fever accompanied by clinical signs, with four of the five classic criteria for complete KD being mucocutaneous, thus creating an important role for dermatologists.
explanation: This reference discusses skin manifestations, which could include peeling, but does not specify the subacute phase duration or joint pain.
- phase: Convalescent
duration: 6-8 weeks
notes: Symptoms resolve, but coronary artery abnormalities may persist
evidence:
- reference: PMID:28580712
reference_title: "Kawasaki disease: State of the art."
supports: PARTIAL
snippet: Kawasaki disease is an acute febrile arteritis of childhood that can result in coronary artery aneurysms if untreated in the first 10 and ideally 7 days of illness. Kawasaki disease begins as a necrotizing arteritis with neutrophilic infiltrate, followed by subacute/chronic changes and luminal myofibroblastic proliferation that can cause coronary artery stenosis.
explanation: The literature indicates that Kawasaki disease can lead to coronary artery abnormalities, but it does not specify that the convalescent phase lasts 6-8 weeks. It supports the persistence of coronary artery abnormalities but does not confirm the exact duration of the convalescent phase.
- reference: PMID:17033807
reference_title: "Predictive risk factors for coronary artery abnormalities in Kawasaki disease."
supports: PARTIAL
snippet: Conclusively, the most important predictor of CAA in KD is total duration of fever longer than 8 days. Early identification of IVGG non-responders and active therapeutic intervention for fever in KD cases might decrease the incidence of CAA.
explanation: This reference discusses the importance of early intervention to prevent coronary artery abnormalities but does not provide specific information about the duration of the convalescent phase.
- reference: PMID:29437127
reference_title: "Kawasaki Disease."
supports: NO_EVIDENCE
snippet: Kawasaki Disease.
explanation: This reference does not provide specific information about the duration of the convalescent phase or the persistence of coronary artery abnormalities.
pathophysiology:
- name: Vascular Inflammation
description: Widespread inflammation of medium-sized arteries, including coronary arteries.
cell_types:
- preferred_term: vascular endothelial cell
description: Primary target cells undergoing activation and dysfunction
term:
id: CL:0000071
label: blood vessel endothelial cell
- preferred_term: neutrophil
description: Recruited to vessel walls during necrotizing arteritis phase
term:
id: CL:0000775
label: neutrophil
- preferred_term: monocyte
description: Activated by immune complexes and FcγR signaling
term:
id: CL:0000576
label: monocyte
- preferred_term: macrophage
description: Present in coronary lesions producing cytokines
term:
id: CL:0000235
label: macrophage
biological_processes:
- preferred_term: endothelial cell activation
description: Cytokine-driven upregulation of adhesion molecules and inflammatory mediators
term:
id: GO:0042118
label: endothelial cell activation
- preferred_term: leukocyte adhesion to vascular endothelial cell
description: ICAM-1/VCAM-1 mediated leukocyte recruitment
term:
id: GO:1904996
label: positive regulation of leukocyte adhesion to vascular endothelial cell
- preferred_term: inflammatory response
description: Systemic hyperinflammatory syndrome with cytokine cascades
term:
id: GO:0006954
label: inflammatory response
locations:
- preferred_term: coronary artery
description: Primary site of arteritis and aneurysm formation
term:
id: UBERON:0001621
label: coronary artery
- preferred_term: artery wall
description: All three layers (intima, media, adventitia) undergo inflammation
term:
id: UBERON:0000415
label: artery wall
downstream:
- target: Aneurysm Formation
description: Coronary arteritis causes structural damage to arterial walls leading to dilation and aneurysm formation.
evidence:
- reference: PMID:21447126
reference_title: "Pathogenesis of Kawasaki disease."
supports: SUPPORT
snippet: Histologically, coronary arteritis begins 6-8 days after the onset of KD, and leads immediately to inflammation of all layers of the artery. The inflammation spreads completely around the artery; as a result, structural components of the artery undergo intense damage; the artery then begins to dilate.
explanation: This reference directly establishes the mechanistic link between coronary arteritis and aneurysm formation through structural damage.
evidence:
- reference: PMID:23188196
reference_title: "Kawasaki disease: basic and pathological findings."
supports: SUPPORT
snippet: Kawasaki disease (KD) is considered to be a kind of systemic vasculitis syndrome. It most frequently affects infants and young children and primarily invades medium-sized muscular arteries, including the coronary arteries.
explanation: The literature confirms that Kawasaki disease involves widespread inflammation of medium-sized arteries, including coronary arteries.
- reference: PMID:31599798
reference_title: "One year in review: Kawasaki disease."
supports: SUPPORT
snippet: Kawasaki disease is a childhood vasculitis of unknown origin, whose major complication is the development of coronary artery aneurysms (CAA).
explanation: The literature supports that Kawasaki disease leads to vascular inflammation and aneurysm formation.
- reference: PMID:27090101
reference_title: "[Coronary artery aneurysms probably due to Kawasaki's disease]."
supports: SUPPORT
snippet: Coronary angiography showed multiple aneurysms which suggested sequelae of misdiagnosed Kawasaki disease.
explanation: The case report indicates that Kawasaki disease can lead to aneurysm formation as a result of vascular inflammation.
- reference: PMID:36102118
reference_title: "Long-term vascular dysfunction in Kawasaki disease: systematic review and meta-analyses."
supports: SUPPORT
snippet: Long-term physiological dysfunction in coronary/systemic vasculature may persist in individuals with Kawasaki disease even in the absence of coronary artery abnormalities.
explanation: The literature suggests long-term vascular dysfunction due to Kawasaki disease, supporting the idea of widespread vascular inflammation.
- reference: PMID:35420684
reference_title: "Silent Kawasaki Disease Affecting Multiple Coronary Arteries in a 39-Year-Old Egyptian Woman."
supports: SUPPORT
snippet: Kawasaki disease, an acute febrile illness, can cause vasculitis in the coronary arteries.
explanation: The literature confirms that Kawasaki disease causes inflammation in coronary arteries, leading to complications such as aneurysms.
- reference: PMID:16990356
reference_title: "The pathophysiology of coronary artery aneurysms in Kawasaki disease: role of matrix metalloproteinases."
supports: SUPPORT
snippet: Kawasaki disease is an acute inflammatory syndrome that takes the form of systemic vasculitis, and predominantly affects children. Important complications of this disease are coronary artery dilation and aneurysm formation.
explanation: The literature supports the statement that Kawasaki disease involves widespread vascular inflammation and aneurysm formation.
- name: Immune Response Dysregulation
description: An abnormal immune response leading to vessel wall damage and inflammation.
cell_types:
- preferred_term: CD8-positive, alpha-beta T cell
description: CD8+ T cells present in coronary lesions
term:
id: CL:0000625
label: CD8-positive, alpha-beta T cell
- preferred_term: T-helper 17 cell
description: Th17 expansion associated with coronary damage and IVIG resistance
term:
id: CL:0000899
label: T-helper 17 cell
- preferred_term: regulatory T cell
description: Treg imbalance contributes to immune dysregulation
term:
id: CL:0000815
label: regulatory T cell
- preferred_term: plasmablast
description: Convergent antigen-driven plasmablast responses in some patients
term:
id: CL:0000980
label: plasmablast
- preferred_term: plasma cell
description: IgA plasma cells found in coronary lesions
term:
id: CL:0000786
label: plasma cell
- preferred_term: dendritic cell
description: Involved in antigen presentation and T-cell activation
term:
id: CL:0000451
label: dendritic cell
biological_processes:
- preferred_term: interleukin-1 beta production
description: IL-1β promotes endothelial injury and inflammation
term:
id: GO:0032611
label: interleukin-1 beta production
- preferred_term: tumor necrosis factor production
description: TNF-α induces endothelial activation and NF-κB signaling
term:
id: GO:0032640
label: tumor necrosis factor production
- preferred_term: interleukin-17 production
description: IL-17 from Th17 cells promotes neutrophil recruitment
term:
id: GO:0032620
label: interleukin-17 production
- preferred_term: calcium ion transmembrane transport
description: Dysregulated Ca2+/calcineurin-NFAT signaling pathway
term:
id: GO:0070588
label: calcium ion transmembrane transport
- preferred_term: T cell activation
description: Enhanced T-cell activation via CD40-CD40L co-stimulation
term:
id: GO:0042110
label: T cell activation
- preferred_term: complement activation
description: Complement fixation contributes to vascular injury
term:
id: GO:0006956
label: complement activation
cellular_components:
- preferred_term: NLRP3 inflammasome complex
term:
id: GO:0072559
label: NLRP3 inflammasome complex
evidence:
- reference: PMID:34890998
reference_title: "Atlas of circulating immune cells in Kawasaki disease."
supports: SUPPORT
snippet: Increasing evidence shows that the pathogenesis of Kawasaki disease (KD) is caused by abnormal and unbalanced innate and adaptive immune responses.
explanation: The literature supports the statement that Kawasaki Disease is characterized by immune response dysregulation leading to vessel wall damage and inflammation.
- reference: PMID:30183655
reference_title: "Autoimmune Aspects of Kawasaki Disease."
supports: SUPPORT
snippet: Kawasaki disease (KD) is a vasculitis that is part of systemic vasculitis syndrome. It affects medium-sized vessels and is characterized by hypercytokinemia.
explanation: This reference supports that KD involves immune dysregulation leading to vessel wall damage.
- reference: PMID:30619331
reference_title: "How Should We Classify Kawasaki Disease?"
supports: SUPPORT
snippet: Others have favored an autoreactive hypothesis that KD is triggered by an antigen that shares homology with structures in the vascular wall, and molecular mimicry resulting in an immune response directed to that tissue.
explanation: This supports the notion of an abnormal immune response leading to vessel wall damage in KD.
- reference: PMID:39117827
reference_title: "Kawasaki Disease-Associated Cytokine Storm Syndrome."
supports: SUPPORT
snippet: Kawasaki disease (KD) is a hyperinflammatory syndrome manifesting as an acute systemic vasculitis characterized by fever, nonsuppurative conjunctival injection, rash, oral mucositis, extremity changes, and cervical lymphadenopathy.
explanation: This reference supports the statement by describing KD as a hyperinflammatory syndrome, which involves immune dysregulation.
phenotypes:
- category: Systemic
name: Fever
description: High fever lasting at least 5 days, a mandatory criterion for diagnosis of Kawasaki disease.
frequency: VERY_FREQUENT
diagnostic: true
evidence:
- reference: PMID:30029859
reference_title: "Intestinal Involvement in Kawasaki Disease."
supports: SUPPORT
snippet: Fever, abdominal pain, and vomiting were the most frequent symptoms observed and typical Kawasaki disease signs and symptoms appeared after intestinal complaints in all cases.
explanation: The literature mentions fever as one of the most frequent symptoms observed in Kawasaki disease, supporting the statement that fever is a very frequent systemic diagnostic symptom of Kawasaki disease.
- reference: PMID:31900257
reference_title: "Fifteen-minute consultation: Kawasaki disease: how to distinguish from other febrile illnesses: tricks and tips."
supports: SUPPORT
snippet: The conundrum for acute paediatricians is which clinical features best distinguish the febrile child with possible KD, needing intravenous immunoglobulin, from the many other children with febrile illnesses.
explanation: The literature highlights the challenge of distinguishing Kawasaki disease from other febrile illnesses, indicating that fever is a very frequent systemic diagnostic symptom in Kawasaki disease.
- reference: PMID:26631821
reference_title: "Kawasaki disease in adults: Observations in France and literature review."
supports: SUPPORT
snippet: The main symptoms were fever (100%), exanthema (98%), changes in
the extremities (91%), conjunctivitis (77%), oral cavity changes (89%),
cervical adenitis (55%) and cardiac abnormalities (45%).
explanation: The literature states that fever is present in 100% of the
cases, supporting the statement that fever is a very frequent systemic
diagnostic symptom of Kawasaki disease.
- reference: ORPHA:2331
supports: PARTIAL
snippet: "HP:0001945 | Fever | Frequent (79-30%)"
explanation: Orphanet classifies fever as frequent (79-30%), but clinical
data consistently shows fever in virtually 100% of cases and it is a
mandatory diagnostic criterion. The VERY_FREQUENT classification is
supported by multiple clinical cohort studies.
phenotype_term:
preferred_term: Fever
description: Elevated body temperature above the normal range, typically above 38°C (100.4°F).
term:
id: HP:0001945
label: Fever
- category: Dermatologic
name: Rash
description: Polymorphous exanthem typically affecting the trunk and extremities, without vesicles or crusting.
frequency: VERY_FREQUENT
evidence:
- reference: PMID:26631821
reference_title: "Kawasaki disease in adults: Observations in France and literature review."
supports: SUPPORT
snippet: The main symptoms were fever (100%), exanthema (98%)...
explanation: Exanthema, which refers to a widespread rash, was present in 98% of the adult patients with Kawasaki Disease.
- reference: PMID:1440951
reference_title: "Kawasaki syndrome."
supports: SUPPORT
snippet: We describe a four-year-old girl who presented with fever, a diffuse erythematous maculopapular rash...
explanation: The case description includes a diffuse erythematous maculopapular rash as one of the clinical features.
- reference: PMID:33453126
reference_title: "Kawasaki disease for the paediatric dermatologist: skin manifestations and new insights into the pathophysiology."
supports: SUPPORT
snippet: All children with KD have fever accompanied by clinical signs, with four of the five classic criteria for complete KD being mucocutaneous...
explanation: The abstract emphasizes the mucocutaneous manifestations, which include skin rashes, as critical for diagnosing Kawasaki Disease.
- reference: PMID:23481152
reference_title: "Incomplete Kawasaki disease."
supports: SUPPORT
snippet: This is a report of a 4-year-old Hispanic boy who presented with skin changes to the lips and oral cavity, a generalized rash...
explanation: The case report mentions a generalized rash as one of the symptoms of Kawasaki Disease.
- reference: PMID:32843441
reference_title: "COVID-19 Inflammatory Syndrome With Clinical Features Resembling Kawasaki Disease."
supports: SUPPORT
snippet: Both patients presented with fever lasting >5 days and were found to have rash, conjunctival injection, and swollen lips.
explanation: The patients with COVID-19 inflammatory syndrome had clinical features resembling Kawasaki Disease, including a rash.
phenotype_term:
preferred_term: Skin rash
description: Visible change in skin color or texture, typically involving erythema or papules.
term:
id: HP:0000988
label: Skin rash
- category: Ocular
name: Conjunctivitis
description: Bilateral bulbar conjunctival injection without exudate, typically limbal sparing.
frequency: VERY_FREQUENT
notes: Non-purulent (no pus)
evidence:
- reference: PMID:34814144
reference_title: "Kawasaki Disease and Atopic Diseases: A Systematic Review and Meta-Analysis of Observational Studies."
supports: SUPPORT
snippet: In cross-sectional studies, KD was associated with allergic rhinitis (n = 6; OR, 1.69; 95% CI, 1.52-1.87), asthma (n = 3; OR, 1.72; 95% CI, 1.38-2.14), allergic conjunctivitis (n = 2; OR, 1.95; 95% CI, 1.68-2.27), and atopic dermatitis (n = 3; OR, 1.35; 95% CI, 1.22-1.49).
explanation: The study shows that Kawasaki Disease is associated with allergic conjunctivitis, supporting the statement that conjunctivitis is very frequent in Kawasaki Disease.
- reference: PMID:32843441
reference_title: "COVID-19 Inflammatory Syndrome With Clinical Features Resembling Kawasaki Disease."
supports: SUPPORT
snippet: Both patients presented with fever lasting >5 days and were found to have rash, conjunctival injection, and swollen lips.
explanation: The description of conjunctival injection in patients with Kawasaki Disease supports the statement.
- reference: PMID:7299613
reference_title: "Eye involvement in Kawasaki disease."
supports: SUPPORT
snippet: In a prospective series, ophthalmologic examinations on 10 children
with Kawasaki disease showed that eight had anterior uveitis during the
acute phase of the illness.
explanation: Although the study focuses on anterior uveitis, it indicates
significant ocular involvement in Kawasaki Disease, supporting the
statement indirectly.
- reference: ORPHA:2331
supports: SUPPORT
snippet: "HP:0000509 | Conjunctivitis | Very frequent (99-80%)"
explanation: Orphanet classifies conjunctivitis as very frequent in Kawasaki
disease, consistent with it being one of the five classic diagnostic criteria.
phenotype_term:
preferred_term: Conjunctivitis
description: Inflammation of the conjunctiva resulting in redness and irritation of the eye.
term:
id: HP:0000509
label: Conjunctivitis
- category: Musculoskeletal
name: Swelling of Hands and Feet
description: Acute erythema and induration of the hands and feet with subsequent periungual desquamation.
frequency: VERY_FREQUENT
evidence:
- reference: PMID:1704148
reference_title: "[Kawasaki disease]."
supports: SUPPORT
snippet: 'The six main clinical presentations of Kawasaki disease are: prolonged fever, conjunctivitis, lesions of the oral and pharyngeal mucosa, inflammatory reddening and swelling of the hands and feet, skin rash and cervical lymph node enlargement.'
explanation: The literature explicitly mentions that swelling of the hands and feet is one of the six main clinical presentations of Kawasaki disease.
- reference: PMID:3333141
reference_title: "Pathological features of Kawasaki disease (mucocutaneous lymph node syndrome)."
supports: SUPPORT
snippet: Early clinical features include fever, rash, conjunctival
injection, dry reddened lips, oropharyngeal reddening, enlarged cervical
nodes, and swelling and redness of hands and feet.
explanation: The literature lists swelling and redness of hands and feet as
early clinical features of Kawasaki disease.
- category: Cardiovascular
frequency: OCCASIONAL
name: Coronary Artery Aneurysms
description: Abnormal dilation of coronary arteries that can lead to thrombosis, stenosis, and myocardial infarction.
notes: Can lead to serious heart complications
evidence:
- reference: PMID:10512599
reference_title: "Kawasaki disease."
supports: REFUTE
snippet: Coronary artery aneurysms or ectasia develop in approximately 15-25% of children with the disease.
explanation: The literature indicates that coronary artery aneurysms are a common complication of Kawasaki disease, occurring in 15-25% of cases, which is more frequent than 'occasional'.
- reference: PMID:31732547
reference_title: "Systemic Artery Aneurysms and Kawasaki Disease."
supports: REFUTE
snippet: Twenty-three patients had SAAs, demonstrating an incidence of 14.2% (23 of 162) in patients who were screened at 1 month after onset. The proportion of patients with SAAs was estimated to be 2% (23 of 1148) of all patients with KD.
explanation: The incidence of coronary artery aneurysms (CAAs) in Kawasaki disease is significant, with a notable percentage of patients developing CAAs, indicating that the frequency is more than 'occasional'.
- reference: PMID:34651205
reference_title: "Analysis of multiple organ involvement in Kawasaki disease."
supports: REFUTE
snippet: Among the 640 KD children, most were 1-5 years old (415/640, 64.8%). Children < 1 year old (31.6%) and > 5 years old (28.3%) were more likely to have cardiovascular complications.
explanation: The study shows a high incidence of cardiovascular complications in children with Kawasaki disease, indicating that coronary artery aneurysms and other heart complications are not just occasional.
- reference: PMID:23075819
reference_title: "Kawasaki disease: late cardiovascular sequelae."
supports: REFUTE
snippet: Patients with persistent or remodeled coronary aneurysms after Kawasaki disease have a high rate of complications including thrombosis or stenosis leading to myocardial infarction.
explanation: The literature indicates a high rate of complications from coronary artery aneurysms in Kawasaki disease, suggesting that these complications are not occasional but rather significant.
- category: Hematologic
name: Thrombocytosis
description: Elevated platelet count commonly found in the subacute phase of Kawasaki disease.
frequency: VERY_FREQUENT
notes: Often appears 1-2 weeks after onset
evidence:
- reference: PMID:33527178
reference_title: "Clinical implications of thrombocytosis in acute phase Kawasaki disease."
supports: SUPPORT
snippet: In Kawasaki disease (KD), thrombocytosis is commonly found in the subacute phase.
explanation: Thrombocytosis is a common finding during the subacute phase of KD.
- reference: PMID:6833960
reference_title: "Kawasaki disease."
supports: SUPPORT
snippet: The second, subacute, phase begins with a decline of the acute findings and proceeds with desquamation of rash, joint manifestations, thrombocytosis, and cardiac disease.
explanation: Thrombocytosis occurs during the subacute phase of KD.
- reference: ORPHA:2331
supports: PARTIAL
snippet: "HP:0001894 | Thrombocytosis | Frequent (79-30%)"
explanation: Orphanet classifies thrombocytosis as frequent (79-30%), while
clinical consensus and this entry classify it as very frequent.
Thrombocytosis is near-universal in the subacute phase.
phenotype_term:
preferred_term: Thrombocytosis
description: Abnormally increased platelet count in the blood.
term:
id: HP:0001894
label: Thrombocytosis
- category: Lymphatic
name: Cervical Lymphadenopathy
description: Enlarged cervical lymph nodes, often unilateral, one of the
classic diagnostic criteria for Kawasaki disease. The least common of the
five principal diagnostic features, reported in approximately 50-75% of
cases.
frequency: FREQUENT
notes: Often unilateral presentation
evidence:
- reference: ORPHA:2331
supports: PARTIAL
snippet: "HP:0025289 | Cervical lymphadenopathy | Very frequent (99-80%)"
explanation: Orphanet classifies cervical lymphadenopathy as very frequent
(99-80%), but clinical series report it in 50-75% of cases, making it the
least common of the five classic criteria. FREQUENT is retained based on
published cohort data.
- reference: PMID:26631821
supports: SUPPORT
snippet: The main symptoms were fever (100%), exanthema (98%), changes in
the extremities (91%), conjunctivitis (77%), oral cavity changes (89%),
cervical adenitis (55%) and cardiac abnormalities (45%).
explanation: Cervical adenitis was present in 55% of adult KD cases in this
French cohort.
phenotype_term:
preferred_term: Cervical lymphadenopathy
description: Enlargement of lymph nodes in the neck region.
term:
id: HP:0025289
label: Cervical lymphadenopathy
- category: Cardiovascular
name: Myocarditis
description: Inflammation of the myocardium that can occur during the acute phase of Kawasaki disease.
frequency: OCCASIONAL
evidence:
- reference: ORPHA:2331
supports: SUPPORT
snippet: "HP:0012819 | Myocarditis | Occasional (29-5%)"
explanation: Orphanet classifies myocarditis as occasional in Kawasaki disease.
- reference: PMID:9665974
supports: SUPPORT
snippet: Common cardiovascular manifestations of the illness include myocarditis,
pericardial effusion, and coronary artery aneurysm formation.
explanation: Rowley and Shulman list myocarditis among common cardiovascular
manifestations of Kawasaki syndrome.
phenotype_term:
preferred_term: Myocarditis
description: Inflammation of the cardiac muscle.
term:
id: HP:0012819
label: Myocarditis
- category: Cardiovascular
name: Aneurysm Formation
description: Vascular dilation resulting from inflammatory weakening of vessel walls, affecting coronary and other medium-sized arteries.
frequency: FREQUENT
evidence:
- reference: PMID:31599798
reference_title: "One year in review: Kawasaki disease."
supports: SUPPORT
snippet: Kawasaki disease is a childhood vasculitis of unknown origin, whose major complication is the development of coronary artery aneurysms (CAA).
explanation: This reference directly states that coronary artery aneurysm development is a major complication of Kawasaki disease.
- reference: PMID:21447126
reference_title: "Pathogenesis of Kawasaki disease."
supports: SUPPORT
snippet: Histologically, coronary arteritis begins 6-8 days after the onset of KD, and leads immediately to inflammation of all layers of the artery. The inflammation spreads completely around the artery; as a result, structural components of the artery undergo intense damage; the artery then begins to dilate.
explanation: This reference describes the mechanism by which arterial inflammation leads to dilation and aneurysm formation in Kawasaki disease.
phenotype_term:
preferred_term: Aneurysm Formation
description: Abnormal focal dilation of a blood vessel due to weakening of the vessel wall.
term:
id: HP:0002617
label: Vascular dilatation
- category: Cardiovascular
name: Pericarditis
description: Inflammation of the pericardium occurring during the acute phase
of Kawasaki disease, sometimes with pericardial effusion.
frequency: FREQUENT
evidence:
- reference: ORPHA:2331
supports: SUPPORT
snippet: "HP:0001701 | Pericarditis | Frequent (79-30%)"
explanation: Orphanet classifies pericarditis as frequent in Kawasaki disease.
- reference: PMID:9665974
supports: PARTIAL
snippet: Common cardiovascular manifestations of the illness include myocarditis,
pericardial effusion, and coronary artery aneurysm formation.
explanation: The snippet mentions pericardial effusion rather than
pericarditis per se; pericardial effusion is a frequent accompaniment of
pericarditis but they are distinct entities.
phenotype_term:
preferred_term: Pericarditis
term:
id: HP:0001701
label: Pericarditis
- category: Cardiovascular
name: Arrhythmia
description: Cardiac rhythm disturbances that may occur during the acute or
subacute phase of Kawasaki disease.
frequency: OCCASIONAL
evidence:
- reference: ORPHA:2331
supports: SUPPORT
snippet: "HP:0011675 | Arrhythmia | Occasional (29-5%)"
explanation: Orphanet classifies arrhythmia as occasional in Kawasaki disease.
phenotype_term:
preferred_term: Arrhythmia
term:
id: HP:0011675
label: Arrhythmia
- category: Cardiovascular
name: Abnormal Heart Valve Morphology
description: Valvular abnormalities including mitral regurgitation that may
occur in the acute phase of Kawasaki disease.
frequency: FREQUENT
evidence:
- reference: ORPHA:2331
supports: SUPPORT
snippet: "HP:0001654 | Abnormal heart valve morphology | Frequent (79-30%)"
explanation: Orphanet classifies abnormal heart valve morphology as frequent
in Kawasaki disease.
phenotype_term:
preferred_term: Abnormal heart valve morphology
term:
id: HP:0001654
label: Abnormal heart valve morphology
- category: Cardiovascular
name: Congestive Heart Failure
description: Heart failure that may occur in severe cases of Kawasaki disease,
particularly with significant myocarditis or coronary artery involvement.
frequency: OCCASIONAL
evidence:
- reference: ORPHA:2331
supports: SUPPORT
snippet: "HP:0001635 | Congestive heart failure | Occasional (29-5%)"
explanation: Orphanet classifies congestive heart failure as occasional in
Kawasaki disease.
phenotype_term:
preferred_term: Congestive heart failure
term:
id: HP:0001635
label: Congestive heart failure
- category: Dermatologic
name: Palmoplantar Erythema
description: Erythema of the palms and soles, a hallmark feature of the acute
phase of Kawasaki disease.
frequency: VERY_FREQUENT
evidence:
- reference: ORPHA:2331
supports: SUPPORT
snippet: "HP:0025493 | Palmoplantar erythema | Very frequent (99-80%)"
explanation: Orphanet classifies palmoplantar erythema as very frequent in
Kawasaki disease.
phenotype_term:
preferred_term: Palmoplantar erythema
term:
id: HP:0025493
label: Palmoplantar erythema
- category: Oropharyngeal
name: Cheilitis
description: Erythema, dryness, and fissuring of the lips, one of the classic
mucocutaneous diagnostic criteria for Kawasaki disease.
frequency: VERY_FREQUENT
evidence:
- reference: ORPHA:2331
supports: SUPPORT
snippet: "HP:0100825 | Cheilitis | Very frequent (99-80%)"
explanation: Orphanet classifies cheilitis as very frequent in Kawasaki disease.
- reference: PMID:1440951
supports: SUPPORT
snippet: We describe a four-year-old girl who presented with fever, a
diffuse erythematous maculopapular rash, bilateral nonpurulent bulbar
conjunctivitis, dry, red, fissured lips, a tongue with a strawberry
'appearance', an erythematous pharynx, indurative erythema, and edema and
desquamation of the face, hands and feet.
explanation: Dry, red, fissured lips are described as a presenting feature
of Kawasaki syndrome.
- reference: PMID:26631821
supports: SUPPORT
snippet: The main symptoms were fever (100%), exanthema (98%), changes in
the extremities (91%), conjunctivitis (77%), oral cavity changes (89%),
cervical adenitis (55%) and cardiac abnormalities (45%).
explanation: Oral cavity changes (including lip involvement) were present in
89% of cases, supporting very frequent classification.
phenotype_term:
preferred_term: Cheilitis
term:
id: HP:0100825
label: Cheilitis
- category: Oropharyngeal
name: Strawberry Tongue
description: Erythematous tongue with prominent papillae, a characteristic
oral finding in Kawasaki disease.
frequency: FREQUENT
evidence:
- reference: ORPHA:2331
supports: SUPPORT
snippet: "HP:0031042 | Strawberry tongue | Frequent (79-30%)"
explanation: Orphanet classifies strawberry tongue as frequent in Kawasaki disease.
- reference: PMID:15835487
supports: SUPPORT
snippet: The disease can present with protean clinical manifestations which
include high grade fever (for at least 5 days), rash, redness of the lips
and a typical strawberry tongue, cervical lymph node enlargement (often
unilateral), swelling over the hands/feet and, later a characteristic
peripheral desquamation over the fingers and toes.
explanation: Strawberry tongue is listed as a typical clinical manifestation
of Kawasaki disease.
phenotype_term:
preferred_term: Strawberry tongue
term:
id: HP:0031042
label: Strawberry tongue
- category: Oropharyngeal
name: Pharyngitis
description: Erythema and inflammation of the pharynx, part of the diffuse
oropharyngeal involvement in the acute phase of Kawasaki disease.
frequency: VERY_FREQUENT
evidence:
- reference: ORPHA:2331
supports: PARTIAL
snippet: "HP:0100776 | Recurrent pharyngitis | Very frequent (99-80%)"
explanation: Orphanet lists recurrent pharyngitis (HP:0100776) as very
frequent, but KD pharyngitis is acute, not recurrent. HP:0025439
(Pharyngitis) is used here as the more accurate term. The frequency
data supports pharyngeal involvement being very frequent.
phenotype_term:
preferred_term: Pharyngitis
term:
id: HP:0025439
label: Pharyngitis
- category: Oropharyngeal
name: Glossitis
description: Inflammation of the tongue contributing to the characteristic oral
mucosal changes in Kawasaki disease.
frequency: FREQUENT
evidence:
- reference: ORPHA:2331
supports: SUPPORT
snippet: "HP:0000206 | Glossitis | Frequent (79-30%)"
explanation: Orphanet classifies glossitis as frequent in Kawasaki disease.
phenotype_term:
preferred_term: Glossitis
term:
id: HP:0000206
label: Glossitis
- category: Dermatologic
name: Scaling Skin on Fingertip
description: Desquamation beginning at the tips of fingers and toes, spreading
to palms and soles during the subacute recovery phase. A hallmark late
finding in Kawasaki disease.
frequency: FREQUENT
notes: Particularly on the fingers and toes, often during the subacute phase
evidence:
- reference: ORPHA:2331
supports: SUPPORT
snippet: "HP:0025525 | Scaling skin on fingertip | Frequent (79-30%)"
explanation: Orphanet classifies fingertip scaling as frequent in Kawasaki disease.
- reference: PMID:3333141
supports: SUPPORT
snippet: Peeling of skin of fingers and toes, arthralgia, and marked
thrombocytosis are frequent 1-2 weeks after onset.
explanation: Peeling of fingers is described as frequent 1-2 weeks after
onset of Kawasaki disease.
- reference: PMID:6833960
supports: SUPPORT
snippet: The second, subacute, phase begins with a decline of the acute
findings and proceeds with desquamation of rash...
explanation: Desquamation is a frequent dermatologic manifestation during
the subacute phase of Kawasaki disease.
- reference: PMID:37065507
supports: SUPPORT
snippet: Kawasaki disease's clinical manifestations range from oral skin
disease to the blistering of the mucosa, symptoms involving the hands and
the feet, skin disease of the palms and soles, a desquamative rash...
explanation: Desquamative rash involving hands, feet, palms, and soles is
described as a clinical manifestation of Kawasaki disease.
phenotype_term:
preferred_term: Scaling skin on fingertip
term:
id: HP:0025525
label: Scaling skin on fingertip
- category: Dermatologic
name: Abnormality of Nail Color
description: Nail changes including Beau's lines and discoloration observed
during convalescence of Kawasaki disease.
frequency: FREQUENT
evidence:
- reference: ORPHA:2331
supports: SUPPORT
snippet: "HP:0100643 | Abnormality of nail color | Frequent (79-30%)"
explanation: Orphanet classifies nail color abnormalities as frequent in
Kawasaki disease.
phenotype_term:
preferred_term: Abnormality of nail color
term:
id: HP:0100643
label: Abnormality of nail color
- category: Musculoskeletal
name: Palmar Edema
description: Swelling of the palms with induration, a distinctive finding in
the acute phase of Kawasaki disease.
frequency: FREQUENT
evidence:
- reference: ORPHA:2331
supports: SUPPORT
snippet: "HP:0025538 | Palmar edema | Frequent (79-30%)"
explanation: Orphanet classifies palmar edema as frequent in Kawasaki disease.
phenotype_term:
preferred_term: Palmar edema
term:
id: HP:0025538
label: Palmar edema
- category: Musculoskeletal
name: Plantar Edema
description: Swelling of the soles with induration, accompanying palmar edema
in the acute phase of Kawasaki disease.
frequency: FREQUENT
evidence:
- reference: ORPHA:2331
supports: SUPPORT
snippet: "HP:0025537 | Plantar edema | Frequent (79-30%)"
explanation: Orphanet classifies plantar edema as frequent in Kawasaki disease.
phenotype_term:
preferred_term: Plantar edema
term:
id: HP:0025537
label: Plantar edema
- category: Gastrointestinal
name: Diarrhea
description: Gastrointestinal involvement with diarrhea is a common
extracardiac manifestation of Kawasaki disease.
frequency: FREQUENT
evidence:
- reference: ORPHA:2331
supports: SUPPORT
snippet: "HP:0002014 | Diarrhea | Frequent (79-30%)"
explanation: Orphanet classifies diarrhea as frequent in Kawasaki disease.
- reference: PMID:30029859
supports: PARTIAL
snippet: Fever, abdominal pain, and vomiting were the most frequent symptoms
observed and typical Kawasaki disease signs and symptoms appeared after
intestinal complaints in all cases.
explanation: The snippet documents GI involvement in KD but mentions
abdominal pain and vomiting rather than diarrhea specifically.
phenotype_term:
preferred_term: Diarrhea
term:
id: HP:0002014
label: Diarrhea
temporality: ACUTE
- category: Gastrointestinal
name: Abdominal Pain
description: Abdominal pain occurring in Kawasaki disease, sometimes preceding
the classic diagnostic features and leading to diagnostic confusion.
frequency: FREQUENT
evidence:
- reference: ORPHA:2331
supports: SUPPORT
snippet: "HP:0002027 | Abdominal pain | Frequent (79-30%)"
explanation: Orphanet classifies abdominal pain as frequent in Kawasaki disease.
- reference: PMID:30029859
supports: SUPPORT
snippet: Fever, abdominal pain, and vomiting were the most frequent symptoms
observed and typical Kawasaki disease signs and symptoms appeared after
intestinal complaints in all cases.
explanation: Abdominal pain is one of the most frequent gastrointestinal
symptoms in Kawasaki disease.
phenotype_term:
preferred_term: Abdominal pain
term:
id: HP:0002027
label: Abdominal pain
- category: Gastrointestinal
name: Nausea and Vomiting
description: Nausea and vomiting occurring as part of gastrointestinal
involvement in Kawasaki disease.
frequency: OCCASIONAL
evidence:
- reference: ORPHA:2331
supports: SUPPORT
snippet: "HP:0002017 | Nausea and vomiting | Occasional (29-5%)"
explanation: Orphanet classifies nausea and vomiting as occasional in Kawasaki
disease.
phenotype_term:
preferred_term: Nausea and vomiting
term:
id: HP:0002017
label: Nausea and vomiting
- category: Hepatic
name: Hepatitis
description: Hepatic inflammation manifesting as elevated transaminases,
occurring as an extracardiac complication of Kawasaki disease.
frequency: OCCASIONAL
evidence:
- reference: ORPHA:2331
supports: SUPPORT
snippet: "HP:0012115 | Hepatitis | Occasional (29-5%)"
explanation: Orphanet classifies hepatitis as occasional in Kawasaki disease.
- reference: PMID:36557034
supports: SUPPORT
snippet: Out of these six KD patients, there were
two patients complicated with hepatitis and one patient with gallbladder
hydrops. Different clinical features including jaundice (n = 3) and hepatomegaly
(n = 4) were also observed.
explanation: Case series confirms hepatitis and hepatomegaly as hepatobiliary
complications of Kawasaki disease.
phenotype_term:
preferred_term: Hepatitis
term:
id: HP:0012115
label: Hepatitis
- category: Hepatic
name: Jaundice
description: Yellowing of the skin and sclera due to hepatobiliary involvement
in Kawasaki disease.
frequency: OCCASIONAL
evidence:
- reference: ORPHA:2331
supports: SUPPORT
snippet: "HP:0000952 | Jaundice | Occasional (29-5%)"
explanation: Orphanet classifies jaundice as occasional in Kawasaki disease.
- reference: PMID:36557034
supports: SUPPORT
snippet: Different clinical features including jaundice (n = 3) and hepatomegaly
(n = 4) were also observed.
explanation: Jaundice was observed in KD patients with hepatobiliary
manifestations.
phenotype_term:
preferred_term: Jaundice
term:
id: HP:0000952
label: Jaundice
- category: Hepatic
name: Cholecystitis
description: Gallbladder inflammation including hydrops that may complicate
Kawasaki disease.
frequency: OCCASIONAL
evidence:
- reference: ORPHA:2331
supports: SUPPORT
snippet: "HP:0001082 | Cholecystitis | Occasional (29-5%)"
explanation: Orphanet classifies cholecystitis as occasional in Kawasaki disease.
phenotype_term:
preferred_term: Cholecystitis
term:
id: HP:0001082
label: Cholecystitis
- category: Renal
name: Proteinuria
description: Protein in the urine reflecting renal involvement in the systemic
vasculitis of Kawasaki disease.
frequency: VERY_FREQUENT
evidence:
- reference: ORPHA:2331
supports: SUPPORT
snippet: "HP:0000093 | Proteinuria | Very frequent (99-80%)"
explanation: Orphanet classifies proteinuria as very frequent in Kawasaki disease.
- reference: PMID:27287282
supports: SUPPORT
snippet: Genitourinary
involvement in patients with Kawasaki disease is typically limited to sterile
pyuria and proteinuria.
explanation: Proteinuria is described as a typical genitourinary finding in
Kawasaki disease.
phenotype_term:
preferred_term: Proteinuria
term:
id: HP:0000093
label: Proteinuria
- category: Renal
name: Sterile Pyuria
description: White blood cells in the urine without bacterial infection,
reflecting urinary tract inflammation in Kawasaki disease.
frequency: OCCASIONAL
evidence:
- reference: ORPHA:2331
supports: SUPPORT
snippet: "HP:0100586 | Sterile pyuria | Occasional (29-5%)"
explanation: Orphanet classifies sterile pyuria as occasional in Kawasaki disease.
- reference: PMID:23390440
supports: SUPPORT
snippet: Kawasaki disease (KD) is a systemic vasculitis and affects many organ
systems. It often presents sterile pyuria, microscopic hematuria, and
proteinuria due to renal involvement.
explanation: Sterile pyuria is a recognized renal manifestation of Kawasaki
disease.
phenotype_term:
preferred_term: Sterile pyuria
term:
id: HP:0100586
label: Sterile pyuria
- category: Musculoskeletal
name: Arthritis
description: Non-erosive, self-limiting arthritis affecting predominantly the
knees, ankles, and hips, occurring in 2-31% of children with Kawasaki disease.
frequency: FREQUENT
evidence:
- reference: ORPHA:2331
supports: SUPPORT
snippet: "HP:0001369 | Arthritis | Frequent (79-30%)"
explanation: Orphanet classifies arthritis as frequent in Kawasaki disease.
- reference: PMID:31974671
supports: PARTIAL
snippet: Eight hundred sixty-five children (male:female 29:11) were diagnosed with
KD during this period-of these, 40 (4.6%) had arthritis.
explanation: This cohort shows 4.6% incidence (OCCASIONAL range), while
ORPHA classifies arthritis as frequent. The wide reported range (2-31%)
across studies suggests variability in ascertainment.
phenotype_term:
preferred_term: Arthritis
term:
id: HP:0001369
label: Arthritis
- category: Musculoskeletal
name: Arthralgia
description: Joint pain without frank arthritis, a common musculoskeletal
complaint in Kawasaki disease, particularly during the subacute phase.
frequency: OCCASIONAL
evidence:
- reference: ORPHA:2331
supports: SUPPORT
snippet: "HP:0002829 | Arthralgia | Occasional (29-5%)"
explanation: Orphanet classifies arthralgia as occasional in Kawasaki disease.
- reference: PMID:3333141
supports: PARTIAL
snippet: Peeling of skin of fingers and toes, arthralgia, and marked
thrombocytosis are frequent 1-2 weeks after onset.
explanation: Arthralgia is described as frequent in this reference, while
ORPHA classifies it as occasional (29-5%). The discrepancy may reflect
differences in ascertainment criteria.
phenotype_term:
preferred_term: Arthralgia
term:
id: HP:0002829
label: Arthralgia
- category: Hematologic
name: Leukocytosis
description: Elevated white blood cell count with neutrophilic predominance,
reflecting the systemic inflammatory response in Kawasaki disease.
frequency: FREQUENT
evidence:
- reference: ORPHA:2331
supports: SUPPORT
snippet: "HP:0001974 | Leukocytosis | Frequent (79-30%)"
explanation: Orphanet classifies leukocytosis as frequent in Kawasaki disease.
phenotype_term:
preferred_term: Leukocytosis
term:
id: HP:0001974
label: Increased total leukocyte count
- category: Systemic
name: Vasculitis
description: Systemic medium-vessel vasculitis, the defining feature of
Kawasaki disease affecting coronary and other medium-sized arteries.
frequency: VERY_FREQUENT
evidence:
- reference: ORPHA:2331
supports: SUPPORT
snippet: "HP:0002633 | Vasculitis | Very frequent (99-80%)"
explanation: Orphanet classifies vasculitis as very frequent in Kawasaki
disease, consistent with vasculitis being the defining pathological feature.
phenotype_term:
preferred_term: Vasculitis
term:
id: HP:0002633
label: Vasculitis
- category: Systemic
name: Fatigue
description: Generalized fatigue and malaise accompanying the systemic
inflammatory response in Kawasaki disease.
frequency: FREQUENT
evidence:
- reference: ORPHA:2331
supports: SUPPORT
snippet: "HP:0012378 | Fatigue | Frequent (79-30%)"
explanation: Orphanet classifies fatigue as frequent in Kawasaki disease.
phenotype_term:
preferred_term: Fatigue
term:
id: HP:0012378
label: Fatigue
- category: Systemic
name: Edema
description: Peripheral edema of the extremities occurring during the acute
phase of Kawasaki disease.
frequency: FREQUENT
evidence:
- reference: ORPHA:2331
supports: SUPPORT
snippet: "HP:0000969 | Edema | Frequent (79-30%)"
explanation: Orphanet classifies edema as frequent in Kawasaki disease.
phenotype_term:
preferred_term: Edema
term:
id: HP:0000969
label: Edema
- category: Neurological
name: Irritability
description: Extreme irritability in affected children, a notable neurological
feature that may precede or accompany the acute febrile phase.
frequency: OCCASIONAL
evidence:
- reference: ORPHA:2331
supports: SUPPORT
snippet: "HP:0000737 | Irritability | Occasional (29-5%)"
explanation: Orphanet classifies irritability as occasional in Kawasaki disease.
phenotype_term:
preferred_term: Irritability
term:
id: HP:0000737
label: Irritability
- category: Neurological
name: Aseptic Meningitis
description: Cerebrospinal fluid pleocytosis without bacterial infection,
occurring as a neurological complication of Kawasaki disease.
frequency: OCCASIONAL
evidence:
- reference: ORPHA:2331
supports: SUPPORT
snippet: "HP:0001287 | Meningitis | Occasional (29-5%)"
explanation: Orphanet classifies meningitis as occasional in Kawasaki disease.
- reference: PMID:33530798
supports: SUPPORT
snippet: Aseptic meningitis (AM) is an uncommon feature of KD.
explanation: Full-text directly characterizes aseptic meningitis as an
uncommon but recognized feature of Kawasaki disease.
phenotype_term:
preferred_term: Aseptic meningitis
term:
id: HP:0001287
label: Meningitis
- category: Neurological
name: Cranial Nerve Paralysis
description: Rare neurological complication of Kawasaki disease, most commonly
affecting the facial nerve (VII), associated with more severe disease
and coronary artery involvement.
frequency: OCCASIONAL
evidence:
- reference: ORPHA:2331
supports: SUPPORT
snippet: "HP:0006824 | Cranial nerve paralysis | Occasional (29-5%)"
explanation: Orphanet classifies cranial nerve paralysis as occasional in
Kawasaki disease.
- reference: PMID:31364426
supports: SUPPORT
snippet: Kawasaki disease (KD) is an acute multisystem vasculitic syndrome
that predominantly affects infants and young children. Neurological
complications are rare in patients with KD and the diagnosis is challenging.
explanation: Case report with literature review documents bilateral facial
nerve palsy and meningitis as rare neurological complications of KD.
phenotype_term:
preferred_term: Cranial nerve paralysis
term:
id: HP:0006824
label: Cranial nerve paralysis
- category: Hematologic
name: Hypoalbuminemia
description: Decreased serum albumin levels reflecting systemic inflammation
and capillary leak in Kawasaki disease.
frequency: FREQUENT
evidence:
- reference: ORPHA:2331
supports: SUPPORT
snippet: "HP:0003073 | Hypoalbuminemia | Frequent (79-30%)"
explanation: Orphanet classifies hypoalbuminemia as frequent in Kawasaki disease.
phenotype_term:
preferred_term: Hypoalbuminemia
term:
id: HP:0003073
label: Hypoalbuminemia
biochemical:
- name: C-Reactive Protein (CRP)
presence: Elevated
context: Indicator of inflammation
evidence:
- reference: PMID:34078404
reference_title: "The occurrence of coronary artery lesions in Kawasaki disease based on C-reactive protein levels: a retrospective cohort study."
supports: SUPPORT
snippet: CAL were found in 12.9 and 18.3% of the high and low CRP patients, respectively (p < 0.001), based on z-scores; and in 9.9 and 12.5%, respectively (p = 0.001), based on the Japanese criteria in the acute phase.
explanation: The study indicates that CRP levels are elevated in Kawasaki Disease patients, with specific percentages of high and low CRP levels noted.
- reference: PMID:39117827
reference_title: "Kawasaki Disease-Associated Cytokine Storm Syndrome."
supports: SUPPORT
snippet: Kawasaki disease (KD) is a hyperinflammatory syndrome manifesting as an acute systemic vasculitis characterized by fever, nonsuppurative conjunctival injection, rash, oral mucositis, extremity changes, and cervical lymphadenopathy.
explanation: The abstract describes KD as a hyperinflammatory syndrome, implying elevated inflammatory markers such as CRP.
- reference: PMID:37551875
reference_title: "N-Terminal Pro-Brain Natriuretic Peptide Levels in Kawasaki Disease, Sepsis and Other Febrile Illnesses."
supports: SUPPORT
snippet: Complete blood count, C-reactive protein (CRP), liver and renal function tests, serum electrolytes, chest X-ray, NT-proBNP level, Bactec blood culture, urine microscopy and culture along with detailed physical examination was done for all cases and control.
explanation: The study includes CRP as part of the diagnostic tests for Kawasaki Disease, indicating its relevance as an inflammatory marker.
- reference: PMID:34731266
reference_title: "Clinical indications for Kawasaki disease in febrile infants aged less than three months."
supports: SUPPORT
snippet: The KD group had a significantly higher level of initial c-reactive protein (CRP) compared to the BI and NBI groups, with a cutoff value of 4.85 mg/dL in comparison with the BI group and 3.32 mg/dL in comparison with the NBI group.
explanation: The study provides specific CRP levels that are elevated in Kawasaki Disease compared to bacterial and non-bacterial infections.
- name: Erythrocyte Sedimentation Rate (ESR)
presence: Elevated
context: Indicator of inflammation
evidence:
- reference: PMID:36604937
reference_title: "Neutrophil-Lymphocyte Ratio for Predicting Coronary Artery Lesions in Children With Kawasaki Disease."
supports: SUPPORT
snippet: NLR >/=2.08 was 82% sensitive and 80% specific in predicting CAL. ESR >/=88 mm/h was 85% sensitive and 64% specific in predicting IVIg resistance.
explanation: The study indicates that ESR is elevated in Kawasaki Disease and can be used to predict IVIg resistance.
- reference: PMID:33413220
reference_title: "Clinical aspects for differential diagnosis of Kawasaki disease shock syndrome: a case control study."
supports: SUPPORT
snippet: In comparison between KDSS and TSS, patients with KDSS had a significantly higher erythrocyte sedimentation rate (ESR) and significantly lower creatinine.
explanation: The study shows that patients with Kawasaki Disease Shock Syndrome (KDSS) have significantly higher ESR levels.
- reference: PMID:15677370
reference_title: "High-dose intravenous immunoglobulin downregulates the activated levels of inflammatory indices except erythrocyte sedimentation rate in acute stage of Kawasaki Disease."
supports: SUPPORT
snippet: The erythrocyte sedimentation rate (ESR) increased significantly 24 h after IVIG, and the elevated level was sustained for 7 days.
explanation: This reference shows that ESR levels are elevated during the acute stage of Kawasaki Disease.
- name: Platelet Count
presence: Elevated
context: Often seen in the subacute phase
evidence:
- reference: PMID:33527178
reference_title: "Clinical implications of thrombocytosis in acute phase Kawasaki disease."
supports: SUPPORT
snippet: In Kawasaki disease (KD), thrombocytosis is commonly found in the subacute phase.
explanation: The abstract states that thrombocytosis (elevated platelet count) is commonly found in the subacute phase of Kawasaki disease.
- reference: PMID:6833960
reference_title: "Kawasaki disease."
supports: SUPPORT
snippet: The second, subacute, phase begins with a decline of the acute findings and proceeds with desquamation of rash, joint manifestations, thrombocytosis, and cardiac disease.
explanation: The text explicitly mentions that thrombocytosis occurs during the subacute phase of Kawasaki disease.
diagnosis:
- name: Echocardiogram
description: Cardiac ultrasound to detect coronary artery dilation, aneurysms, and other cardiac abnormalities.
notes: Used to check for coronary artery involvement
evidence:
- reference: PMID:28921836
reference_title: "Clinical assessment of coronary arteries in Kawasaki disease: Focus on echocardiographic assessment."
supports: SUPPORT
snippet: Echocardiography is an excellent noninvasive imaging modality for evaluation and follow-up of cardiac lesions, especially coronary artery changes occurring as a result of Kawasaki disease.
explanation: The reference clearly states that echocardiography is used to evaluate coronary artery changes in Kawasaki disease, supporting the statement.
- name: Blood Tests
description: Laboratory assessment including CRP, ESR, platelet count, and white blood cell count to evaluate inflammation.
notes: Elevated inflammatory markers (CRP and ESR)
evidence:
- reference: PMID:36569014
reference_title: "Kawasaki disease without changes in inflammatory biomarkers: A case report."
supports: PARTIAL
snippet: Since KD is a disease caused by arterial inflammation, many patients with KD have elevated levels of inflammatory biomarkers, such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and serum amyloid A protein (SAA) in blood tests.
explanation: The literature suggests that many patients with Kawasaki Disease have elevated inflammatory markers, but it also reports cases where such elevations are not observed.
- reference: PMID:34854940
reference_title: "Assessing the Association of Kawasaki Disease Symptoms and Echocardiographic Findings."
supports: SUPPORT
snippet: Thrombocytosis, conjunctivitis, and oral and/or pharyngeal erythema and/or strawberry tongue were associated with higher rates of echocardiographic abnormalities.
explanation: The study indicates that inflammatory markers are associated with echocardiographic abnormalities in Kawasaki Disease, supporting the statement.
- reference: PMID:33481812
reference_title: "A novel score system of blood tests for differentiating Kawasaki disease from febrile children."
supports: SUPPORT
snippet: We obtained eight independent predictors (platelets, eosinophil, alanine aminotransferase, C-reactive protein, hemoglobin, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and monocyte).
explanation: CRP is identified as one of the independent predictors for Kawasaki Disease, supporting the statement.
- reference: PMID:27881022
reference_title: "Elevated serum YKL-40 levels in patients with Kawasaki disease."
supports: SUPPORT
snippet: YKL-40 concentration in the serum of KD patients significantly increased during the acute disease phase compared with those of disease controls and healthy controls.
explanation: The study supports the presence of elevated inflammatory markers in Kawasaki Disease patients.
- reference: PMID:37188888
reference_title: "Prokineticin 2 as a potential biomarker for the diagnosis of Kawasaki disease."
supports: SUPPORT
snippet: PK2 can significantly predict Kawasaki disease independently of CRP and ESR (p < 0.0001).
explanation: CRP and ESR are mentioned as markers that can independently predict Kawasaki Disease, supporting the statement.
genetic:
- name: ITPKC
association: Risk variant reduces negative regulation of Ca2+/NFAT signaling leading to enhanced T-cell activation
notes: Associated with coronary lesions and hyperinflammation; rationale for calcineurin inhibitors
- name: FCGR2A
association: Mediates immune-complex driven neutrophil/monocyte activation
notes: Mechanistic basis for IVIG competing at FcγRs; genetic association with susceptibility
- name: FCGR3A
association: Mediates immune-complex driven neutrophil/monocyte activation
notes: Involved in FcγR signaling and immune complex handling
- name: BLK
association: B lymphoid tyrosine kinase involved in B-cell receptor signaling
notes: Genetic locus implicated in altered B-cell/plasmablast responses
- name: CD40
association: Promotes B/T cell and endothelial activation via CD40-CD40L co-stimulation
notes: CD40L on T cells linked to endothelial cell activation and inflammation
- name: HLA-B
association: HLA associations support antigen-driven or superantigen-like T-cell responses
notes: Shapes disease susceptibility; useful for dissecting trigger(s) and host response subtypes
- name: CASP3
association: Implicated in endothelial cell apoptosis and vascular remodeling during acute vasculitis
notes: Apoptosis modulation is investigational
- name: ORAI1
association: Store-operated calcium entry component; variants alter SOCE leading to dysregulated Ca2+ signaling
notes: Heightened T-cell responses contribute to hyperinflammation
- name: STIM1
association: Store-operated calcium entry component; variants alter SOCE leading to dysregulated Ca2+ signaling
notes: Points to SOCE or calcineurin/NFAT modulation as therapeutic option
- name: TGFBR2
association: TGF-β receptor involved in endothelial-to-mesenchymal transition
notes: Drives EndMT and luminal myofibroblast proliferation leading to stenosis/aneurysm formation
- name: SMAD3
association: TGF-β signaling mediator involved in vascular remodeling
notes: Anti-fibrotic or TGF-β pathway modulation is theoretical target
- name: TGFB2
association: TGF-β signaling involved in chronic vascular remodeling
notes: Informs long-term vascular remodeling targets
- name: IL1B
association: IL-1β promotes endothelial injury, inflammation and remodeling
notes: Direct IL-1 blockade (anakinra) has mechanistic and clinical rationale for IVIG-resistant KD
- name: IL1R1
association: IL-1 receptor; downstream of inflammasome activation
notes: IL-1 pathway is therapeutic target
- name: TNF
association: Induces endothelial cell expression of ICAM-1/VCAM-1, iNOS and proinflammatory cascade
notes: Anti-TNF therapy (infliximab) used for IVIG-resistant cases
- name: IL17A
association: Th17 expansion and elevated IL-17 associate with coronary damage and IVIG resistance
notes: Promotes neutrophil recruitment; IL-17/IL-23 pathway inhibitors are investigational
- name: IL23A
association: IL-23 involved in Th17 axis and IL-17 signaling
notes: Potential investigational approach in select patients
- name: NLRP3
association: NLRP3 inflammasome activation leads to IL-1β release and pyroptosis
notes: NLRP3 or IL-1 pathway inhibition offers mechanistic target
- name: NOS3
association: Reduced eNOS expression/activity leads to decreased NO, vasoconstriction, and thrombosis
notes: Supports vascular-protective strategies and monitoring of endothelial function
- name: ICAM1
association: Upregulated by TNF/IL-1 leading to leukocyte recruitment and endothelial dysfunction
notes: Adhesion-inflammation axis is biomarker and potential target
- name: VCAM1
association: Upregulated by TNF/IL-1 leading to vascular injury
notes: Part of adhesion-inflammation axis
treatments:
- name: Intravenous Immunoglobulin (IVIG)
description: First-line treatment to reduce inflammation and risk of coronary artery complications.
evidence:
- reference: PMID:23283289
reference_title: "Advances in the treatment of Kawasaki disease."
supports: SUPPORT
snippet: Intravenous immunoglobulin (IVIG) and aspirin is the standard initial therapy in the treatment of Kawasaki disease.
explanation: The literature confirms that IVIG is part of the standard initial therapy for Kawasaki disease, aimed at reducing inflammation and preventing coronary artery complications.
- reference: PMID:38135926
reference_title: "Early Clinical Evaluation of Coronary Artery Lesions in Kawasaki Disease."
supports: SUPPORT
snippet: For KD patients, male, children aged 3 to 9 years, and those with fever longer than 6 days before intravenous immunoglobulin (IVIG) use were more likely to have CAL.
explanation: The study discusses the use of IVIG and its timing in relation to the risk of coronary artery lesions, supporting its role in reducing such risks.
- reference: PMID:24034380
reference_title: "Kawasaki disease: part II. Complications and treatment."
supports: SUPPORT
snippet: The standard of care for treatment is intravenous immunoglobulin plus aspirin, but adding corticosteroids may provide additional benefit for high-risk patients.
explanation: The literature states that IVIG is the standard of care for treating Kawasaki disease to reduce coronary artery complications.
- reference: PMID:34535199
reference_title: "Shaanxi Provincial Diagnosis and Treatment Center of Kawasaki Disease."
supports: SUPPORT
snippet: Intravenous immunoglobulin (IVIG) has become an effective treatment regimen, which can effectively reduce the incidence of cardiovascular complications.
explanation: The literature confirms that IVIG is effective in reducing cardiovascular complications in Kawasaki disease.
- reference: PMID:32888683
reference_title: "Update on the Management of Kawasaki Disease."
supports: SUPPORT
snippet: Treatment of Kawasaki disease (KD) with intravenous immunoglobulin (IVIG) administered within the initial 10 days of fever onset decreases the risk of coronary artery aneurysms (CAAs) from ∼ 25% to less than 5%.
explanation: The literature provides evidence that IVIG significantly reduces the risk of coronary artery complications when administered early.
treatment_term:
preferred_term: intravenous immunoglobulin therapy
description: Treatment of disease through the administration of medications.
term:
id: MAXO:0001480
label: immunoglobulin infusion therapy
- name: Aspirin
description: Used in high doses for its anti-inflammatory and antipyretic effects, followed by a lower dose to prevent blood clots.
evidence:
- reference: PMID:9513217
reference_title: "Kawasaki disease: a dangerous acute childhood illness."
supports: SUPPORT
snippet: Treatment includes the hospitalization of the child and subsequent administration of high doses of aspirin and intravenous immunoglobulin. With recovery, aspirin doses are reduced and the child may be monitored at home with outpatient follow-up.
explanation: This reference confirms that high doses of aspirin are used initially for Kawasaki disease, followed by lower doses after recovery.
- reference: PMID:10935427
reference_title: "New perspectives in the drug treatment of Kawasaki disease."
supports: SUPPORT
snippet: Conventional therapy for KD includes intravenous gammaglobulin (2 g/kg as a single dose over 12 hours) and aspirin (acetylsalicylic acid; high dose until the fourteenth day of illness then low dose).
explanation: This reference also supports the statement that high doses of aspirin are used initially, followed by lower doses.
- reference: PMID:32159800
reference_title: "What dose of aspirin should be used in the initial treatment of Kawasaki disease? A meta-analysis."
supports: PARTIAL
snippet: Low-dose aspirin plus IVIG might be as effective as high-dose aspirin plus IVIG for the initial treatment of Kawasaki disease. Considering that high-dose aspirin may cause more adverse reactions than low-dose aspirin, low-dose aspirin plus IVIG should be recommended as the first-line therapy in the initial treatment of Kawasaki disease.
explanation: This reference suggests that low-dose aspirin might be equally effective as high-dose aspirin and should be recommended to avoid adverse reactions, indicating a shift in treatment preference.
- reference: PMID:28043685
reference_title: "Medium- or Higher-Dose Acetylsalicylic Acid for Acute Kawasaki Disease and Patient Outcomes."
supports: PARTIAL
snippet: The use of medium- or higher-dose ASA in acute Kawasaki disease did not prevent CAA. A future randomized controlled trial is needed to determine the optimum dose of ASA.
explanation: This reference indicates that higher doses of aspirin did not prevent coronary artery aneurysms and suggests the need for further research to determine the optimal dose.
treatment_term:
preferred_term: cardiovascular agent therapy
description: Treatment using medications that affect the cardiovascular system, including antiplatelet agents.
term:
id: MAXO:0000181
label: cardiovascular agent therapy
- name: Anakinra
description: IL-1 receptor antagonist used for IVIG-resistant Kawasaki disease to block IL-1-mediated endothelial injury.
notes: Mechanistic rationale based on NLRP3 inflammasome and IL-1β pathway activation
treatment_term:
preferred_term: Pharmacotherapy
description: Treatment using IL-1 pathway inhibition for refractory inflammation.
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: anakinra
term:
id: NCIT:C38717
label: Anakinra
- name: Cyclosporine
description: Calcineurin inhibitor used to modulate Ca2+/NFAT signaling in genetically susceptible patients.
notes: Targets dysregulated calcium signaling pathway; used for IVIG-resistant cases
treatment_term:
preferred_term: Pharmacotherapy
description: Treatment using calcineurin inhibition to reduce T-cell activation.
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: cyclosporine
term:
id: NCIT:C406
label: Cyclosporine
- name: Corticosteroids
description: Used in cases resistant to IVIG or with severe inflammation.
evidence:
- reference: PMID:31914832
reference_title: "The role of corticosteroids in the treatment of Kawasaki disease."
supports: SUPPORT
snippet: We suggest using methylprednisolone pulse therapy as an alternative rescue therapy for immunoglobulin-resistant KD, as well as identifying high-risk patients who need initial corticosteroid with IVIG treatment with an adequate route, dose, and duration.
explanation: The literature supports the use of corticosteroids in cases of Kawasaki Disease that are resistant to IVIG or in high-risk patients with severe inflammation.
- reference: PMID:29101553
reference_title: "Treatment Options for Resistant Kawasaki Disease."
supports: SUPPORT
snippet: '"Resistant" Kawasaki disease is defined by the American Heart Association as failure to respond within 36 h following the first dose of intravenous immunoglobulin. The optimal management of resistant Kawasaki disease remains uncertain, the outcomes are potentially serious, and the cost of some treatments is considerable.'
explanation: This reference discusses the management of resistant Kawasaki Disease, which includes considering corticosteroid use.
- reference: PMID:33541111
reference_title: "Risk Factors of Coronary Artery Abnormalities and Resistance to Intravenous Immunoglobulin Plus Corticosteroid Therapy in Severe Kawasaki Disease: An Analysis of Post RAISE."
supports: SUPPORT
snippet: To prevent CAA, more intensified or adjunctive therapies using other agents, such as pulsed methylprednisolone, ciclosporin, infliximab, and Anakinra, should be considered for patients with these risk factors.
explanation: This reference mentions the use of pulsed methylprednisolone (a corticosteroid) for patients with Kawasaki Disease who are at risk of developing coronary artery abnormalities, indicating severe inflammation.
treatment_term:
preferred_term: systemic corticosteroid therapy
description: Treatment using corticosteroids to reduce inflammation in refractory cases.
term:
id: NCIT:C122080
label: Systemic Corticosteroid Therapy
- name: Infliximab
description: Anti-TNF monoclonal antibody used for IVIG-resistant Kawasaki
disease to block TNF-mediated endothelial activation and inflammation.
notes: Second-line treatment for refractory KD; targets TNF-driven
inflammation
evidence:
- reference: PMID:33541111
supports: SUPPORT
snippet: To prevent CAA, more
intensified or adjunctive therapies using other agents, such as pulsed
methylprednisolone, ciclosporin, infliximab, and Anakinra, should be considered
for patients with these risk factors.
explanation: Infliximab is listed among adjunctive therapies for IVIG-resistant
KD patients at risk of coronary artery abnormalities.
treatment_term:
preferred_term: Pharmacotherapy
description: Anti-TNF biologic therapy for refractory Kawasaki disease.
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: infliximab
term:
id: NCIT:C1789
label: Infliximab
notes: Prompt treatment is crucial to prevent coronary artery complications.
Long-term follow-up may be necessary for some patients.
disease_term:
preferred_term: Kawasaki disease
description: An acute febrile vasculitis of childhood primarily affecting medium-sized arteries with risk of coronary artery complications.
term:
id: MONDO:0012727
label: Kawasaki disease
classifications:
harrisons_chapter:
- classification_value: CARDIOVASCULAR
- classification_value: IMMUNE_RHEUMATOLOGIC
references:
- reference: DOI:10.1016/j.pedneo.2023.05.002
title: Pathophysiological and clinical point of view on Kawasaki disease and MIS-C
findings: []
- reference: DOI:10.1111/1756-185x.14816
title: 'An update on understanding the <scp>pathophysiology</scp> in Kawasaki disease: Possible role of immune complexes in coronary artery lesion revisited'
findings: []
- reference: DOI:10.1172/jci176938
title: The etiologies of Kawasaki disease
findings: []
- reference: DOI:10.3389/fimmu.2024.1323171
title: FCGR2/3 polymorphisms are associated with susceptibility to Kawasaki disease but do not predict intravenous immunoglobulin resistance and coronary artery aneurysms
findings: []
- reference: DOI:10.3389/fped.2024.1415941
title: Research perspective in the clinical management of Kawasaki disease
findings: []
- reference: DOI:10.3390/ijms252413322
title: 'Endothelial Dysfunction: Molecular Mechanisms and Therapeutic Strategies in Kawasaki Disease'
findings: []
- reference: DOI:10.52533/johs.2024.40109
title: Etiology, Pathophysiology, Diagnosis and Management of Kawasaki Disease
findings: []
Kawasaki disease is an acute, self-limited, systemic vasculitis of medium-sized arteries with a predilection for the coronary arteries, driven by a genetically primed, dysregulated innate and adaptive immune response to one or more infectious/environmental triggers that culminates in endothelial activation/dysfunction and layered coronary-artery wall inflammation and remodeling (necrotizing arteritis, subacute/chronic vasculitis, luminal myofibroblast proliferation) (burns2024theetiologiesof pages 4-5, paolini2024endothelialdysfunctionmolecular pages 2-4, paolini2024endothelialdysfunctionmolecular pages 4-5, philip2023anupdateon pages 4-6). Recent reviews emphasize heterogeneous etiologies with epidemiologic signals for a respiratory-transmitted trigger and convergent, antigen-driven plasmablast responses in some patients, while genetic susceptibility (e.g., ITPKC, FCGR, HLA, CD40, BLK; Ca2+/NFAT, FcγR, and TGF-β pathway variants) shapes endotypes and clinical risk (burns2024theetiologiesof pages 4-5, paolini2024endothelialdysfunctionmolecular pages 2-4, vankova2023pathophysiologicalandclinical pages 13-17). Endothelial dysfunction is central: proinflammatory cytokines (IL‑1β, TNF‑α, IL‑6, IL‑17) induce adhesion molecules (ICAM‑1/VCAM‑1), oxidative stress, reduced NO bioavailability, and endothelin‑1 signaling, promoting leukocyte recruitment, thrombosis, and arterial stiffness; endothelial-to-mesenchymal transition and TGF‑β-mediated remodeling contribute to aneurysm/stenosis (paolini2024endothelialdysfunctionmolecular pages 4-5, paolini2024endothelialdysfunctionmolecular pages 5-7). Immune-complex deposition with FcγR-driven myeloid activation, complement fixation, platelet aggregation, and neutrophil degranulation likely participate in coronary arteritis; coronary lesions contain monocytes/macrophages, dendritic cells, neutrophils, CD8+ T cells, and IgA plasma cells (philip2023anupdateon pages 4-6). Emerging work highlights gut barrier dysfunction and dysbiosis as upstream modulators of systemic inflammation in KD, with putative links to Th17 skewing and treatment resistance, although causality requires further study (vankova2023pathophysiologicalandclinical pages 13-17).
Table: Table mapping principal genes/proteins to pathways, mechanistic roles in Kawasaki disease, therapeutic implications, and source DOIs (2023–2024); useful for ontology annotation and evidence‑based knowledgebase curation. - Chemical entities (examples): acetylsalicylic acid (aspirin) for antiplatelet/anti-inflammatory effects; intravenous immunoglobulin (IVIG) competing at FcγRs and modulating immune pathways; infliximab (anti‑TNF) to blunt TNF‑driven endothelial activation; anakinra (IL‑1 receptor antagonist) to inhibit IL‑1–mediated endothelial injury; corticosteroids to broadly suppress cytokine networks; cyclosporine to inhibit calcineurin–NFAT signaling in genetically susceptible endotypes; nitric oxide bioavailability and endothelin‑1 as endothelial tone mediators (paolini2024endothelialdysfunctionmolecular pages 5-7, yi2024researchperspectivein pages 2-3, paolini2024endothelialdysfunctionmolecular pages 4-5, paolini2024endothelialdysfunctionmolecular pages 2-4). - Cell types: vascular endothelial cells; neutrophils; monocytes/macrophages and dendritic cells; CD8+ T cells; Th17 and regulatory T cells; B cells/plasmablasts including IgA plasma cells (philip2023anupdateon pages 4-6, paolini2024endothelialdysfunctionmolecular pages 2-4, vankova2023pathophysiologicalandclinical pages 13-17, burns2024theetiologiesof pages 4-5). - Anatomical locations: coronary artery wall (intima, media, adventitia), vasa vasorum, bronchial epithelium (candidate antigen reservoirs), intestinal barrier/gut mucosa; myocardium and other medium/small arteries may be involved (philip2023anupdateon pages 4-6, burns2024theetiologiesof pages 4-5, vankova2023pathophysiologicalandclinical pages 13-17, paolini2024endothelialdysfunctionmolecular pages 2-4).
Notes on open questions - A single KD trigger remains unproven; evidence suggests heterogeneous etiologies and host-response endotypes that may benefit from tailored immunomodulation (burns2024theetiologiesof pages 4-5). Better integration of endothelial biology with gut–immune axes and precise genetic risk mapping may enable endotype-specific therapies (paolini2024endothelialdysfunctionmolecular pages 2-4, vankova2023pathophysiologicalandclinical pages 13-17).
References
(burns2024theetiologiesof pages 4-5): Jane C. Burns. The etiologies of kawasaki disease. The Journal of Clinical Investigation, Mar 2024. URL: https://doi.org/10.1172/jci176938, doi:10.1172/jci176938. This article has 54 citations.
(paolini2024endothelialdysfunctionmolecular pages 2-4): Lucia Paolini, Fiorentina Guida, Antonino Calvaruso, Laura Andreozzi, Luca Pierantoni, Marcello Lanari, and Marianna Fabi. Endothelial dysfunction: molecular mechanisms and therapeutic strategies in kawasaki disease. International Journal of Molecular Sciences, 25:13322, Dec 2024. URL: https://doi.org/10.3390/ijms252413322, doi:10.3390/ijms252413322. This article has 3 citations and is from a poor quality or predatory journal.
(paolini2024endothelialdysfunctionmolecular pages 4-5): Lucia Paolini, Fiorentina Guida, Antonino Calvaruso, Laura Andreozzi, Luca Pierantoni, Marcello Lanari, and Marianna Fabi. Endothelial dysfunction: molecular mechanisms and therapeutic strategies in kawasaki disease. International Journal of Molecular Sciences, 25:13322, Dec 2024. URL: https://doi.org/10.3390/ijms252413322, doi:10.3390/ijms252413322. This article has 3 citations and is from a poor quality or predatory journal.
(philip2023anupdateon pages 4-6): Saji Philip, Ankur Jindal, and Raman Krishna Kumar. An update on understanding the pathophysiology in kawasaki disease: possible role of immune complexes in coronary artery lesion revisited. International Journal of Rheumatic Diseases, 26:1453-1463, Jul 2023. URL: https://doi.org/10.1111/1756-185x.14816, doi:10.1111/1756-185x.14816. This article has 16 citations and is from a peer-reviewed journal.
(vankova2023pathophysiologicalandclinical pages 13-17): Lenka Vaňková, Jiří Bufka, and Věra Křížková. Pathophysiological and clinical point of view on kawasaki disease and mis-c. Pediatrics & Neonatology, 64:495-504, Sep 2023. URL: https://doi.org/10.1016/j.pedneo.2023.05.002, doi:10.1016/j.pedneo.2023.05.002. This article has 14 citations and is from a peer-reviewed journal.
(paolini2024endothelialdysfunctionmolecular pages 5-7): Lucia Paolini, Fiorentina Guida, Antonino Calvaruso, Laura Andreozzi, Luca Pierantoni, Marcello Lanari, and Marianna Fabi. Endothelial dysfunction: molecular mechanisms and therapeutic strategies in kawasaki disease. International Journal of Molecular Sciences, 25:13322, Dec 2024. URL: https://doi.org/10.3390/ijms252413322, doi:10.3390/ijms252413322. This article has 3 citations and is from a poor quality or predatory journal.
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