What are the other Names for this Condition? (Also known as/Synonyms)

• Infantile Polyarteritis Nodosa
• Kawasaki Syndrome
• Mucocutaneous Lymph Node Syndrome (MCLS)

What is Kawasaki Disease? (Definition/Background Information)

• Kawasaki Disease is an autoimmune disease with a characteristic syndrome consisting of fever, conjunctivitis (inflammation of the conjunctiva, or membranes on the insides of the eyelids and the whites of the eyes), lymphadenopathy (swelling of lymph nodes), and “exanthema” (widespread rash)
• Less commonly, it may be associated with inflammation of the heart, gut, skin, brain, lungs, joints, and genitalia
• The signs and symptoms are due to abnormal inflammation of the blood vessels all over the body. The exact cause of blood vessel inflammation is debated
• In spite of extensive symptoms, this disorder is treatable with a majority of the individuals recovering, without any complications
• Kawasaki Disease is not contagious, which means that it cannot spread from person to person

Who gets Kawasaki Disease? (Age and Sex Distribution)

• Kawasaki Disease normally affects children younger than 5 years
• Both boys and girls can develop this disease; although boys are affected slightly more than girls, in a 1.5: 1 male-female ratio
• This disease was originally described in Asia, but is being increasingly diagnosed in other parts of the world

What are the Risk Factors for Kawasaki Disease? (Predisposing Factors)

The risk factors of Kawasaki Disease include:

• Young age of the individual is a major predisposing factor
• Pre-existing viral infections and other autoimmune diseases
• It is found that individuals belonging to a certain ethnicity have an increased risk for Kawasaki disease. These include children of Asian origin, such as Japanese or Korean

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Kawasaki Disease? (Etiology)

The exact cause of Kawasaki Disease occurrence is unknown. However, the following are speculated to be potential causes of this disease:

• Immunological cause – interaction of antigen and super-antigen. This means that the body may be tricked to attack its own cells by immune cells, which are responsible in protecting the body against outside threats
• Viral and bacterial infection
• Genetic cause – Japanese children seem to be affected more, irrespective of the geographical region where they are present

What are the Signs and Symptoms of Kawasaki Disease?

The signs and symptoms of Kawasaki Disease include the following classic characteristics:

• Fever
• Exanthema (widespread rashes on the body)
• Red tongue/lips/oral mucosa
• Cervical lymphadenopathy (swollen lymph nodes in the neck)
• Conjunctivitis

Kawasaki Disease presents itself in 3 distinct phases: The first day of fever is taken as the first day of the disease.

First Phase (Acute)

• High and persistent fever (38-40 deg. C), which responds partially to Ibuprofen/Tylenol
• Red eye – conjunctivitis which is not painful, and there is no discharge
• Uveitis, keratic precipitates – inflammation inside the eye
• Red, swollen, cracked, bleeding lips, tongue, and red mucous membranes
• Swollen cervical lymph glands
• Red swollen skin on the palms of hand and feet soles

Second Phase (Subacute)

• Abdominal pain, diarrhea, vomiting, and pancreatitis
• Peeling in the skin of hands and feet
• Joint pains

Third Phase (Convalescent)

• Symptoms gradually get better; Kawasaki Disease progresses to a stage of recovery, in about 8 weeks
• Complications may occur, if disease does not resolve by this time

How is Kawasaki Disease Diagnosed?

A diagnosis of Kawasaki Disease requires fever lasting more than 5 days and a fulfillment of four or more of the following criteria; with exclusion of other diseases having similar signs and symptoms:

• Swelling or redness in the extremities
• Polymorphous (having a variety of forms) exanthema
• Bilateral conjunctival injection (accumulation of fluid in the conjunctiva of both the eyes)
• Changes (e.g., color) in tongue, lips, oral mucosa
• Cervical lymphadenopathy

Children with fever and having fewer than four of the above listed criteria, can be diagnosed with Kawasaki Disease, if two-dimensional echocardiography or coronary angiography (radiological tests measuring blood flow) can show coronary artery disease. However, it is also important to ensure that the individual does not have other diseases (i.e., other diseases or conditions must be “ruled out”).

Clinical diagnosis is made after eliminating other diseases with similar presentations. Diseases that might be ruled out are toxic shock syndrome, scarlet fever, juvenile rheumatoid, arthritis, measles, tick-borne illnesses (like Rocky Mountain spotted fever). Blood count tests also help to rule out other differentials.

• Blood tests: Anemia, inflammation, increased leukocytes indicates Kawasaki Disease
• Blood test ESR that is elevated
• Blood test CRP that is elevated
• Liver function tests may show signs of hepatic inflammation and low serum albumin
• Electrocardiogram: Kawasaki Disease can cause serious cardiac complications
• Echocardiography: To assess cardiac function and coronary artery aneurysm
• Urinalysis: WBC and protein in urine (pyuria and proteinuria) without bacterial growth
• Lumbar puncture may show finding similar to aseptic meningitis. A culture of cerebrospinal fluid (CSF) will not show any infection when tested, though CSF will show inflammatory cells
• Coronary artery catheterization: It provides a definitive evidence of coronary artery aneurysm, though it is generally not performed
• Temporal artery biopsy

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Kawasaki Disease?

Coronary artery involvement by Kawasaki Disease can lead to serious heart problems. This is the leading cause of heart attacks in children. Below is a summary of potential complications of this condition:

• Heart complications: Inflammation of the heart muscles (myocarditis), heart valve problems (mitral regurgitation), dysrhythmias of the heart
• Inflammation of the heart blood vessels (vasculitis), shock, and vomiting may signify myocardial ischemia or infarction. This may occur within 1 year after the onset of Kawasaki  Disease
• Gastrointestinal complications: Heinoch Schonlein Purpura (inflammation of the gut organs resulting in abdominal pain), intestinal obstruction, intestinal pseudo-obstruction, acute abdomen (sudden onset of abdominal pain)
• Optic complications: Uveitis, iridocyclitis, optic hemorrhage, necrotizing vasculitis, peripheral gangrene (inflammation of internal structures in the eye)
• Neurological complications: Seizure, chorea (abnormal movement of limbs), mental confusion, lethargy, and coma
• Behavioral problems: Anxiety, depression, night terrors, attention deficit, and learning problems
• Approximately 1% of patients may get Kawasaki Disease a second time

How is Kawasaki Disease Treated?

Treatment measures for Kawasaki Disease include:

• Kawasaki Disease is treated with aspirin and intravenous immunoglobulin (IVIg). The aspirin is given to treat coronary artery disease, similar to how adult patients with cardiovascular disease are administered. IVIg, which suppresses inflammation (although the exact mechanism of action is unclear), is given to prevent inappropriate inflammation attacking the coronary arteries. High-dose IVIg results in improvement of fever within 24 hours. Aspirin is less effective than IVIg. Once fever subsides, low dose aspirin has to be taken for 6-8 weeks
• One of the few indications of aspirin in children is Kawasaki Disease, though there is a risk for Reye’s syndrome. Reye’s syndrome is a disease which affects the blood, liver, and brain in children after certain viral diseases
• Vaccination with varicella and influenza are required, as they are responsible for causing Reye’s syndrome
• Kawasaki disease is an autoimmune disease; hence, steroids (intravenous methylprednisolone) may also be used. The use of monoclonal antibodies (infliximab, also called Remicade), are also an option
• Anticoagulant drugs, coronary artery angioplasty, stent placement, and coronary artery bypass graft (surgery to relieve clogged arteries) are reserved for complicated cases with heart problems
• Without treatment 25% of the children develop heart problems

How can Kawasaki Disease be Prevented?

• Kawasaki Disease cannot be prevented
• Although, there is no known means of preventing the development of Kawasaki Disease, medicines such as aspirin can be given to prevent acute attacks and coronary artery disease

What is the Prognosis of Kawasaki Disease? (Outcomes/Resolutions)

• Most children with Kawasaki Disease recover within weeks. Rarely, afflicted children develop serious and life-threatening complications
• Earlier treatment results in better prognosis. Majority of the children, who receive treatment have a complete cure with no residual complications
• Mortality rates without treatment is 1% at 6 weeks; while, mortality rates with treatment is 0.01% (which means that the mortality is very low with treatment)
• There is an overall mortality rate of 2%, due to coronary artery complications
• Children below the age of 6 months or greater than 8 years, have more severe forms of the disease
• The initial size of aneurysm of coronary artery determines whether it will resolve or not. The greater the size, the less likely it is to resolve
• Treatment with intravenous immunoglobulin may cause allergic and non-allergic side effects, fluid retention, or aseptic meningitis. There may be altered liver function, even after treatment

Additional and Relevant Useful Information for Kawasaki Disease:

Treatment with aspirin is known to cause Reye’s syndrome (affects brain, blood, and liver) and hence, aspirin should be avoided.