• Kawasaki Disease is a clinical diagnosis that requires prompt recognition and management.
• It is an acute illness with inflammation of small and medium-sized blood vessels throughout the body, in particular, the coronary arteries.
• Kawasaki disease was previously known as mucocutaneous lymph node syndrome. It was first described in Japan in 1967 by Dr Tomisaku Kawasaki (a Paediatrician).
• 80% of cases occur in children younger than 5 years old with a peak incidence between 1- 2 years. The disease is very uncommon in those over 14 years old and in adults, although there are increasing reported cases of Kawasaki disease in adults post COVID-19 infection.
• The cause of Kawasaki disease remains unknown.
• It is a diagnosis of exclusion.
• Without treatment, Kawasaki disease is usually a self-limiting illness and resolves spontaneously within 4-8 weeks. However, about 20% of untreated cases develop coronary artery damage and approximately 2% of patients will die, most commonly from a heart attack. This outlook has improved significantly with appropriate treatment.

Clinical features

• Kawasaki disease is a multisystem illness with fever and rash, which occurs mainly in children less than 5 years old. Within 3 days of abrupt onset of fever, the other characteristic features usually appear:

Re-activation of BCG site (erythema around BCG scar) is pathognomic for Kawasaki disease.

Not all of the cardinal signs may be present in any one child with Kawasaki disease and not all features may be present at the same time. Some features may appear and disappear before others arise.

Reactivation of BCG siteReactivation of BCG scars, characterised by area of erythema and induration around previous BCG injection site.

• Febrile infant less than 1 year old may present with less than 4 characteristic features. Irritability is one of the features in younger children. Children with Kawasaki disease are often unusually irritable, out of proportion to the other signs exhibited.
• They also have a range of other non-specific symptoms and signs including abdominal pain, diarrhoea, dysuria, arthritis, meningitis or heart failure.

Diagnosis

• The diagnosis can be made when there is FEVER + at least 4 out of the 5 features listed above. One of the most serious complications is the delayed development of coronary artery aneurysms, which will develop in at least 20% of untreated patients.
• There is no specific lab test that establishes the diagnosis of Kawasaki disease. ESR and CRP are usually raised during the first 2 weeks of the illness. Thrombocytosis after Day 10 of the illness is also common. ECG and CXR are the initial cardiological investigations. None of these are specific for Kawasaki disease.
• Atypical/ incomplete Kawasaki disease, in which patients have fever but fewer than 4 out of the 5 cardinal features, are now diagnosed more commonly. In these children, the diagnosis may be supported by findings on an early echocardiogram to detect coronary artery disease or other signs of acute heart disease.

Differential diagnoses

• Some illnesses that might present with some of the features of Kawasaki disease include:
  • Scarlet fever
  • Staphylococcal scalded skin syndrome
  • Measles
  • COVID-19
  • Toxic shock syndrome
  • Juvenile rheumatoid arthritis
  • Other viral exanthems
  • Drug hypersensitivity reaction
  • Steven-Johnson syndrome (SJS)/ Toxic Epidermal Necrolysis (TEN)

Treatment

Treatment is mostly aiming to rapidly switch off the inflammatory process and minimise the risk of coronary artery inflammation/ aneurysm formation. Specific therapy must be given early to be most effective, so it should be given when the diagnosis is strongly suspected.

• Intravenous immunoglobulin (IVIG). If administered with aspirin within 10 days of the onset of fever, IVIG relieves symptoms and reduces the risk of coronary aneurysms in about 10% of children. Once children are treated, they generally improve rapidly. Sometimes, the fever may not respond to the first dose of IVIG within 48- 72 hours or may recur. In this situation, a second dose of IVIG may be given.
• Aspirin. Aspirin should be given in the first week of the illness. There is no evidence that the dose of salicyclic acid effects aneurysm formation. Aspirin dose can be reduced once the fever is under control. Aspirin should be continued for 6 weeks until the child has another echocardiogram (if the initial echocardiogram result is normal). If there are coronary artery aneurysms, the child should continue on low-dose aspirin.
• In refractory cases where a child does not respond to 2 doses of IVIG, IV methylprednisolone or oral prednisolone can be used following discussion with Paediatric Cardiology.

There have been several reported cases where children with Kawasaki disease developed Reye syndrome while on high dose aspirin. Therefore it is important to change to low dose aspirin as soon as possible and warn parents to discontinue aspirin if the child develops influenza or chicken pox.

Complications

The main complications are the development of coronary artery aneurysms. These can lead to angina, myocardial infarction or sudden death. When the child is treated with IVIG and respond quickly to the treatment, the risk of subsequent coronary artery abnormality is reduced to 2- 4% and most of these have mild abnormalities many of which resolve.

Subsequent immunization

• Measles and other live virus vaccines (i.e. varicella) should be deferred for 11 months following high-dose IVIG treatment. Alternatively, a child at high risk of measles could be vaccinated, and then revaccinated again at least 11 months after the administration of IVIG.
• Other routine immunization should not be interrupted
• Annual influenza vaccination is recommended for children with coronary aneurysms on aspirin.

Written by Dr Stanley Leong

Senior Paediatric Registrar and Dermatology Registrar