Kawasaki Disease

Kawasaki disease is an acute, self-limited systemic vasculitis of childhood, predominantly affecting medium-sized arteries. The coronary arteries are the most clinically significant site, because of the risk of aneurysm formation.

It is the leading cause of acquired heart disease in children in high-income settings. It occurs predominantly in children under five years of age, with peak incidence in infancy and early childhood.

The cause remains incompletely understood. It is believed to be an abnormal immune response, triggered by an unidentified infectious agent or agents in a genetically susceptible individual.

Prompt recognition and treatment within the first ten days of illness is essential, because treatment timing is directly related to the reduction in coronary artery aneurysm risk.

Pathophysiology

• An intense, dysregulated systemic inflammatory response produces vasculitis predominantly of medium-sized muscular arteries. The coronary arteries are of greatest concern because of the propensity for aneurysm formation.
• The inflammation progressively destroys the normal arterial wall architecture, including the elastic lamina and smooth muscle. The weakened wall is susceptible to aneurysmal dilation under normal arterial pressure.
• Coronary artery aneurysms carry ongoing long-term risk. Thrombosis with resulting myocardial infarction is the principal mechanism of mortality and morbidity. Stenosis can develop at the margins of the aneurysm as the wall heals with fibrous scarring. The largest aneurysms carry a persistent risk of rupture.
• Prompt treatment aims to prevent aneurysms. Where they develop, structured long-term cardiological surveillance is needed.
• The triggering mechanism remains unidentified. Seasonal clustering, occasional geographic case clustering, and a striking age distribution (predominantly infants and young children) support an infectious or environmental trigger interacting with genetic susceptibility. No single causative agent has been definitively identified.

• Diagnosis requires fever persisting for five days or longer (the essential defining criterion) together with at least four of five additional principal clinical features.
• Bilateral, non-exudative conjunctival injection.
• Changes of the lips and oral cavity: erythema, dryness, and cracking of the lips, and a "strawberry tongue" from prominent, erythematous papillae.
• A polymorphous rash, variable in morphology, though characteristically not vesicular or bullous.
• Changes of the extremities: erythema and oedema of the hands and feet in the acute phase. Characteristic periungual desquamation follows, typically beginning around ten to fourteen days after fever onset. It is a useful but delayed, retrospective diagnostic feature.
• Cervical lymphadenopathy, typically unilateral, with at least one node exceeding 1.5 centimetres in diameter. It is the least consistently present of the five criteria.
• Incomplete (atypical) Kawasaki disease is an important, increasingly recognised presentation. Fever meets the duration criterion but fewer than four of the additional principal features are present.
• It is particularly relevant in infants under one year of age. Paradoxically they have the highest risk of coronary artery complications despite a less complete, more subtle picture.
• Keep a high index of suspicion in any infant with prolonged, otherwise unexplained fever, even when the classical criteria are not fulfilled. Consider supportive laboratory and echocardiographic assessment.
• Supportive clinical features include significant irritability, often disproportionate to the apparent illness and a useful clue in younger infants, and abdominal pain and diarrhoea.
• A subset of children have aseptic meningitis, hepatitis, or arthritis, reflecting the broader systemic inflammation.
• Coronary artery aneurysm is typically clinically silent in the acute phase. It is identified through structured echocardiographic surveillance rather than symptoms, so cardiac imaging is a standard part of assessment and management.

• Diagnosis is clinical, based on fulfilment of the diagnostic criteria, because no single definitive laboratory test exists.
• Exclude alternative diagnoses with an overlapping picture, including scarlet fever, staphylococcal toxic shock syndrome, and certain viral exanthems.
• Supportive laboratory findings are non-specific individually but add support, particularly in incomplete Kawasaki disease. They include marked elevation of inflammatory markers (erythrocyte sedimentation rate and C-reactive protein) and, in some cases, sterile pyuria and mild transaminitis.
• Thrombocytosis characteristically develops later, typically in the second week, rather than at initial presentation.
• Echocardiography is essential in every confirmed or strongly suspected case. Perform it at diagnosis to establish a baseline and screen for early coronary artery involvement.
• Repeat echocardiography at defined intervals, typically at approximately two weeks and again at six to eight weeks after diagnosis. Coronary aneurysms frequently develop or become clearer over this period.
• A normal initial echocardiogram therefore does not exclude later aneurysm, and surveillance imaging remains essential.
• Formal diagnostic criteria for incomplete Kawasaki disease combine supportive laboratory findings and echocardiographic criteria. They guide diagnosis and treatment in children with fever meeting the duration criterion but too few principal features for a classical diagnosis.
• The diagnosis must not be missed in atypical presentations, because delayed or missed treatment carries a significant, preventable coronary artery risk.

• High-dose intravenous immunoglobulin, given as a single infusion, is the cornerstone of treatment. Evidence clearly shows substantial reduction in coronary artery aneurysm risk when it is given within the first ten days of illness. Start it as promptly as possible once the diagnosis is established, because the reduction achieved depends directly on timing.
• High-dose aspirin is given concurrently during the acute febrile phase for its anti-inflammatory benefit. The dose is then reduced to a low, antiplatelet dose once the child has been afebrile for a defined period, typically forty-eight to seventy-two hours.
• Low-dose aspirin generally continues for a minimum of six to eight weeks after diagnosis, or longer where surveillance echocardiography shows coronary artery abnormality, for ongoing antiplatelet benefit in this higher-risk context.
• A proportion of children (generally reported at approximately ten to twenty percent) fail to respond adequately to initial intravenous immunoglobulin, with persistent or recurrent fever. They need additional treatment.
• A second dose of intravenous immunoglobulin is the standard approach for treatment-refractory disease.
• Corticosteroids are increasingly used, either as an adjunct to initial treatment in children at higher risk of immunoglobulin resistance on validated risk scoring systems, or as second-line treatment for confirmed resistance.
• For the most severe, refractory cases, biologic agents including infliximab are used. This reflects an increasingly individualised, risk-stratified approach to treatment intensity.
• Children with a coronary artery aneurysm on surveillance echocardiography need structured long-term cardiological follow up. Surveillance intensity and antithrombotic therapy follow established risk stratification categories and are individualised to aneurysm size and characteristics.
• Antithrombotic therapy ranges from continued low-dose aspirin for smaller aneurysms to more intensive antiplatelet or anticoagulant therapy, including warfarin, for the largest, giant aneurysms, which have a substantially elevated thrombosis risk.
• Cardiology follow up extends through childhood and, for those with confirmed coronary involvement, into adulthood. It addresses surveillance for coronary artery stenosis or thrombosis, and cardiovascular risk factor counselling.
• Depending on the pattern and extent of coronary involvement, consider stress testing or further imaging for myocardial ischaemia.
• The most important modifiable factor in preventing serious long-term cardiac consequences is prompt recognition and treatment within the first ten days of illness.