Kawasaki disease (KD) is a medium vessel vasculitis that primarily occurs in childhood, typically affecting muscular arteries, with a predilection for the coronary arteries. It rarely occurs in adults.
First reported in 1967 by Japanese pediatrician Tomisaku Kawasaki, it was later recognized as a major cause of acquired heart disease in children worldwide. The International Classification of Diseases (ICD-10) code is M30.3.
Epidemiology
The incidence rate varies significantly by region.
| Region | Incidence per 100,000 children under 5 years |
|---|---|
| Japan | Approximately 265 people |
| South Korea | 134 people |
| Taiwan | 83 people |
| United States | Approximately 18 people |
Boys are more susceptible than girls, and most cases occur between 6 months and 5 years of age. Incidence tends to be higher in winter.
The cause remains unknown. A leading theory is that exposure to a pathogen (likely a virus) triggers an inflammatory cascade, leading to immune system dysregulation in genetically susceptible children. Evidence includes differences in incidence among ethnic groups, higher incidence in children with a family history, and genetic predisposition identified through genome-wide association studies.
Kawasaki disease begins with systemic symptoms mainly characterized by fever, accompanied by ocular symptoms.
Kawasaki disease is a clinical diagnosis, made when fever persists for 5 days or more and at least 4 of the following major criteria are present:
Details of ocular symptoms (in over 90% of patients)
Conjunctivitis
Frequency: Most common (approximately 90%)
Characteristics: Bilateral, bulbar conjunctival, non-exudative. Characterized by limbal sparing.
Timing: Appears within a few days after fever onset. Directly correlates with the presence of rash.
Pathology: Neutrophilic rosette formation (observed in conjunctival scrapings).
Anterior Uveitis
Frequency: Up to 70%
Characteristics: Bilateral, Grade 1+ or 2+. Occasionally accompanied by keratic precipitates.
Timing: Occurs within one week after the onset of fever.
Note: The presence of early acute phase findings is useful for confirming the diagnosis of incomplete Kawasaki disease. At least one study has shown a significant correlation with coronary artery dilation.
Other ocular symptoms
Pathophysiology
Exposure of the respiratory or digestive tract to an unknown pathogen in Kawasaki disease is thought to activate B cells in associated lymphoid tissues, leading to their differentiation into IgA-producing plasma cells. These plasma cells enter the circulatory system and, together with T cells, neutrophils, macrophages, and eosinophils, cause infiltrative damage to the arterial wall.
In this process, the inflammatory response within the arterial wall is enhanced, leading to loss of structural integrity, vasodilation, and aneurysm.
Systemic inflammatory response can affect various ocular tissues, including the conjunctiva, cornea, sclera, uvea, vitreous body, retina, optic nerve, extraocular muscles, and periorbital vascular system.
Risk factors
There is no single clinical test that confirms Kawasaki disease. Diagnosis is based on a combination of specific clinical findings.
Characteristic examination findings (not required but for reference)
Echocardiography
Evaluation of coronary artery dilation is essential and is typically performed at diagnosis, before discharge, and at follow-up visits at 2 weeks and 6 weeks.
The broad differential diagnosis of Kawasaki disease includes the following:
A form that meets only part of the diagnostic criteria is called incomplete or atypical. Diagnosis is often delayed, and the risk of coronary artery aneurysms and long-term cardiac complications is high. If there is persistent fever and one or more typical symptoms, Kawasaki disease should be included in the differential diagnosis.
Intravenous immunoglobulin therapy
The mainstay of initial treatment. Administration within 10 days of symptom onset has been shown to reduce the risk of developing coronary artery lesions.
Aspirin
It is used for anti-inflammatory and antiplatelet effects. However, it has not been shown to reduce the risk of developing coronary artery lesions.
Additional treatment for cases unresponsive to intravenous immunoglobulin therapy
If fever persists 36 hours after administration of intravenous immunoglobulin therapy, the following medications may be considered:
Ocular inflammation in Kawasaki disease is often self-limiting and resolves over a period of days to 8 weeks.
Kawasaki disease is a vasculitis of medium-sized arteries, particularly affecting muscular arteries such as the coronary arteries. The core of its pathology is inflammatory infiltration of the arterial wall due to abnormal immune activation.
Molecular-level mechanisms
Exposure to an unknown pathogen → B cell activation and differentiation into IgA-producing plasma cells → Plasma cells infiltrate the arterial wall → Interaction with T cells, neutrophils, macrophages, and eosinophils → Structural damage to the arterial wall, vasodilation, and aneurysm formation
Effects on Ocular Tissues
As part of systemic vasculitis, various ocular vascular systems and inflammatory pathways are affected. From the direct correlation between conjunctivitis and skin rash, it is inferred that there is an overlap of inflammatory pathways in the conjunctiva and skin.
In the acute phase, neutrophilic rosetting may be observed in conjunctival scrapings.
The mechanisms of ptosis are presumed to include destruction of the artery supplying the levator palpebrae superioris muscle, myositis, and immune-mediated neurological lesions.
Myopia has been shown to be more common in patients with a history of Kawasaki disease, and research is advancing to elucidate the mechanism of myopic shift induced by ocular inflammation.
Research on the role of infectious triggers in the etiology of Kawasaki disease is accelerating, as COVID-19-associated multisystem inflammatory syndrome in children presents with clinical features similar to Kawasaki disease.
