Kawasaki disease



Overview.

What is Kawasaki disease?

Definition

Kawasaki disease (KD) is an acute febrile rash disorder characterized by generalized vasculitis.

In developed countries, Kawasaki disease has become the leading cause of acquired heart disease in children.

Incidence

Kawasaki disease occurs in all countries of the world, with a higher incidence in people of Asian descent.

Epidemiologic investigation in China shows that the incidence rate of children under 5 years of age in Beijing from 2000 to 2004 was 49.4/100,000; children under 5 years of age at the onset of the disease accounted for 87.4%.

The ratio of male to female is 1.83:1.

Questions you may be concerned about

Can Kawasaki disease be completely cured?

Kawasaki disease can be completely cured, but there is a possibility of recurrence.

Kawasaki disease is a self-limiting disease. Most children have a good prognosis, but a few children may have a relapse, with 1% to 2% of children experiencing a relapse. Children should follow the doctor’s instructions for regular checkups, which include physical examination, electrocardiogram, echocardiogram, and other tests, to avoid recurrence.

Does Kawasaki disease affect children when they grow up?

Usually, children without coronary artery disease will have no effect when they grow up. Some children with complications may have some effect when they grow up if they are not treated in time.

Children with coronary artery dilatation or coronary aneurysms mostly disappear on their own within 2 years after the disease, but some children may have functional abnormalities such as wall thickening and reduced elasticity, which may lead to symptoms of chest tightness and chest pain. Some children may have huge coronary artery aneurysms, and in severe cases, shock or even sudden death may occur.

What kind of children are susceptible to Kawasaki disease?

The cause of Kawasaki disease is still unclear, and may be related to immunity and infection, so there is no specific group of people who are susceptible to the disease. According to current epidemiologic findings, Kawasaki disease occurs in all countries in the world, with a slightly higher incidence in Asians, and is more common in infants and young children under the age of 4, and more common in males.

What are the symptoms of Kawasaki disease?

The main symptoms of Kawasaki disease include fever, bloodshot eyes, bloodshot lips, and rash.

Children usually have a body temperature of 39-40℃, and the fever may last for one to two weeks, or even longer. Bilateral conjunctival congestion may appear 3-4 days after the onset of the disease, and the ocular symptoms may disappear after the fever subsides; the lips and mouth are flushed, and the mucous membranes are congested; a maculopapular or polymorphic erythematous rash may appear on the trunk of the skin.

What are the risks of Kawasaki disease?

Most of the children with Kawasaki disease can recover after appropriate treatment and no harm is done; some of the children can have complications, Kawasaki disease may be complicated by myocardial infarction, rupture of coronary aneurysm, which is life-threatening; those who have coronary artery vascular injury may have long-term persistent coronary artery injury, chest tightness, chest pain and other symptoms.

Etiology

The cause of the disease is not yet clear, and may be related to infections, such as rickettsiae, staphylococcus, streptococcus and other infections, in addition to genetic and immune factors. Kawasaki disease is not contagious.

Causes

The cause of the disease is not clear, and may be related to infections (bacteria, fungi, viruses, etc.), immunity, genetic factors and so on.

Some scholars believe that it is related to environmental pollution and chemical sensitization.

Pathogenesis

The etiology and pathogenesis of the disease are not yet clear. It may be caused by abnormal activation of the autoimmune system due to one or more infectious factors on the basis of a certain genetic susceptibility.

Genetic factors

Susceptibility genes are mainly genes involved in inflammatory response and genes involved in vascular function.

Genetic polymorphisms in the matrix metalloproteinase gene, angiotensin-converting enzyme gene, and genes for vascular-derived growth factor and its receptor may be associated with Kawasaki disease and its cardiovascular complications.

Immune dysregulation

The immune system is in an activated state during the acute phase and plays an important role in pathogenesis.

Increased serum immunoglobulins (IgM, IgA, IgG, IgE) and cytokines (tumor necrosis factor-α, interleukin, gamma-interferon, etc.) induce endothelial cells to express and produce neoantigens; B cells in turn secrete autoantibodies, which lead to cytolytic cytotoxic effects on endothelial cells and trigger vascular inflammation.

These cytokines can induce the production of acute temporal response proteins, causing an acute febrile response.

Symptoms

The symptoms include persistent high fever, skin rash, and a congested, raised tongue resembling a strawberry. There may also be bloodshot eyes, red lips, mouth ulcers, swollen lymph nodes in the neck, and peeling of the hands and feet.

Main Symptoms

Fever

Body temperature up to 39～40℃.

It lasts for 7～14 days or longer.

Body temperature does not return to normal after antibiotic treatment.

Bilateral bulbar conjunctival congestion

Appears 3～4 days after onset of illness.

No purulent discharge.

Symptoms may disappear in some children after the fever subsides.

Changes in lips and mouth

Lips are flushed, chapped or bleeding.

Diffuse congestion of the oral mucosa.

The papillae of the tongue are raised and congested, with prune-like or strawberry-like changes.

Hand and Foot Symptoms

In the acute phase, there is flushing of the hands and feet and hard swelling of the finger (toe) ends.

In the recovery phase, perinail desquamation occurs.

Skin changes

A maculopapular or polymorphic erythematous rash is present, mostly on the trunk.

It often appears in the first week, and the duration of symptoms is about 1 week.

Flushing and flaking of the perineal and perianal skin may occur.

Redness at the scar of the original BCG vaccination (prone to occur 3 months to 3 years after vaccination).

Complications

Cardiovascular complications

The leading cause of death in children with Kawasaki disease.

Myocarditis, pericarditis, endocarditis, and coronary artery disease may occur.

Of these, the most predominant are coronary artery lesions, which often appear within 10 days of onset. Usually there are no typical clinical symptoms, and some of them may present with myocardial infarction manifestations, severe chest pain, near-death sensation, irritability, and pallor.

Digestive system complications

There may be paralytic intestinal obstruction, manifested by obvious abdominal distension, persistent abdominal distension, vomiting and so on.

Respiratory system complications

There may be interstitial pneumonia, acute respiratory failure, etc., manifested by coughing, coughing up sputum, chest tightness, dyspnea and so on.

Nervous system complications

Aseptic meningitis causes severe headache, cervical rigidity, nausea, vomiting; when combined with brain parenchyma involvement, facial nerve paralysis, ptosis, aphasia, hemiparesis, intracranial hemorrhage and so on.

Others

Occasionally, arthritis symptoms such as joint redness, swelling, pain, and localized elevated skin temperature are seen.

Consultation

Usually consult the pediatric internal medicine department. When the child develops persistent high fever, skin rash, conjunctival congestion and other symptoms, medical attention should be sought as soon as possible.

Department of Medicine

Pediatrics

Children with symptoms such as fever that does not go away, redness at the BCG vaccination site, flushing or hard swelling of the hands and feet are advised to consult a doctor as soon as possible.

Emergency Department

Sudden severe chest pain, pale face, etc. It is recommended to go to the Emergency Department or call 120 emergency immediately.

Preparation for medical treatment

Preparation for medical consultation: registration, preparation of documents, common problems

Tips for seeking medical treatment

Children are often unable to express their feelings clearly, and may appear to be crying repeatedly, refusing to eat, depressed, etc. Parents need to pay more attention.

Do not abuse medication without the doctor’s permission, so as to prevent the medication from interfering with the relevant examinations and the diagnosis and treatment of the disease.

Preparation List

Symptom list

Pay particular attention to the time of onset of symptoms, special manifestations, etc.

Is there a fever? How long has it lasted? What is the highest temperature?

Is there any cough, runny nose, vomiting?

What is your mental, sleep and dietary status?

Are there any symptoms of rash, red eyes?

Medical History Checklist

Is there any relevant medical history in the family?

Are there any drug or food allergies?

What vaccinations have you received? Any abnormal reaction after vaccination?

Are there any other medical conditions?

Checklist

Test results of the past 6 months, which can be brought to the doctor’s office.

Routine blood tests

Immunologic examination

Liver Function

Coagulation Function

Echocardiogram

Coronary Angiogram

Chest X-ray

Cardiac Magnetic Resonance Imaging

Medication List

Medication used in the last 3 months, if available in boxes or packages, bring with you to the doctor’s office

Antiplatelet agents: aspirin, dipyridamole

Glucocorticoids: methylprednisolone, prednisone

Diagnosis

Diagnosis of Kawasaki disease is based on signs and symptoms, including persistent high fever, rash, conjunctival congestion, strawberry tongue, enlarged lymph nodes in the neck, and coronary artery damage may be seen on imaging.

Diagnosis is based on

Medical history

The etiology and mechanism of Kawasaki disease are not clear, and there is no clear medical history.

Clinical manifestations

Persistent fever.

Bilateral bulbar conjunctival congestion.

Acute phase flushing of hands and feet, hard swelling of finger and toe ends; recovery phase membranous desquamation of finger (toe) ends.

Polymorphic rash with redness at BCG inoculation sites.

Congestion and cracking of lips and mouth, diffuse congestion of oral mucosa, protruding and congested tongue papillae, prune or strawberry tongue.

Non-suppurative cervical lymph node enlargement.

Laboratory Tests

Blood tests

Blood routine: blood leukocytosis, predominantly neutrophils; some have mild anemia and thrombocytosis.

Erythrocyte sedimentation rate (hematocrit): increased speed.

C-reactive protein: C-reactive protein is elevated in the acute phase.

Coagulation function: increased plasma fibrinogen may be found.

Liver function: elevated serum transaminases may be found.

Brain natriuretic peptide (BNP) with N-terminal brain natriuretic peptide precursor (NT-pro BNP): elevated.

Immunologic tests

Elevated serum IgG, IgM, IgA, IgE and circulating immune complexes.

Helper T-cell 2 (Th2) class cytokines, such as interleukin-6 (IL-6), are markedly elevated, and total complement and C3 are normal or elevated.

Electrocardiography

Nonspecific ST-T changes may be detected early in the disease.

When pericarditis occurs, extensive ST-segment elevation and low voltage may be found.

When myocardial infarction occurs, marked ST-segment elevation, T-wave inversion, and abnormal Q-waves can be found.

Imaging

Echocardiography

The most important auxiliary examination.

In the acute stage, pericardial effusion, increased left ventricular diameter, mitral, aortic or tricuspid regurgitation are occasionally seen.

Some children may have abnormal changes in the coronary arteries, such as coronary artery dilatation, coronary artery aneurysm formation.

Coronary Z-scores can objectively reflect the lesions.

Coronary angiography

It is used to understand the extent of coronary artery lesions and to guide treatment.

It is suitable for those who have multiple coronary artery aneurysms found by ultrasonography or those who have myocardial ischemia manifested by electrocardiogram.

CT

Used to understand the condition of coronary artery stenosis, thrombosis, vascular calcification, etc. It is better than echocardiography.

Precautions: Remove metal objects, such as necklaces and earrings, from the body before the examination.

Chest X-ray

It is used to understand the changes in the morphology and structure of the heart and lungs.

Increased texture, blurring or flaky shadows in the lungs can be seen; the heart shadow may be enlarged.

Precautions

Special groups, such as infants, young children, pregnant women, should be cautious of X-ray examination.

Remove metal objects from the chest before the examination, such as necklaces around the neck and undergarments with metal braces.

Cardiac Magnetic Resonance Imaging (MRI)

This test can accurately observe myocardial damage and myocardial ischemia.

Precautions

It is necessary to remove any metal or magnetic objects from the body in advance.

Those who have pacemakers, metal or magnetic objects on their bodies cannot undergo the test.

Diagnostic Criteria

Kawasaki disease

Kawasaki disease is diagnosed when fever is present for more than 5 days with 4 of the following 5 clinical manifestations, after excluding other diseases.

Changes in the extremities: flushing of the hands and feet in the acute phase, hard edema of the ends of the fingers and toes; membranous desquamation of the ends of the fingers (toes) in the recovery phase.

Polymorphic rash.

Ocular conjunctival congestion, nonpurulent.

Congestion and cracking of lips and mouth, diffuse congestion of oral mucosa, protruding and congested tongue papillae in the form of prune or strawberry tongue.

Non-suppurative lymph node enlargement in the neck.

Note: The diagnosis of Kawasaki disease can also be confirmed if fewer than 4 of the 5 clinical signs are present, but there is coronary artery damage on echocardiography and other diseases are excluded.

Intravenous immunoglobulin (IVIG) non-reactive Kawasaki disease

IVIG nonresponsive Kawasaki disease should be considered if the child receives a standard dose of IVIG within 10 days of onset of illness and has a temperature higher than 38°C 36 to 48 hours after infusion, or has a second fever 2 to 7 days after administration, and meets at least one of the diagnostic criteria for Kawasaki disease.

Stages

The pathologic process can be divided into four stages, mainly systemic vasculitis, easily involving the coronary arteries.

Stage I: 1 to 9 days, inflammation appears around small arteries, and small nutrient arteries and veins of coronary artery branches are invaded; inflammatory reactions appear in the pericardium, myocardial interstitium and endocardium.

Stage II: 12 to 25 days, full-layer vasculitis occurs in the major branches of the coronary arteries, and thrombi and aneurysms may form.

Stage III: 28 to 31 days, the arterial inflammation gradually subsides, thrombus and granulation form, fibrous tissue proliferation, and marked thickening of the endothelium, leading to partial or complete obstruction of the coronary arteries.

Stage IV: months to years, the lesion gradually heals, myocardial scar formation, and the blocked artery may recanalize.

Differential Diagnosis

Systemic juvenile idiopathic arthritis

Similarities: fever, rash, joint swelling and pain, headache, nausea, vomiting.

Differences: Systemic juvenile idiopathic arthritis with fever for at least 2 weeks at a time, associated joint swelling and pain, positive rheumatoid factor tests, and imaging of the joints can further clarify the diagnosis.

Scarlet fever

Similarities: fever, rash.

Differences: Scarlet fever is characterized by the following.

History of upper respiratory tract infection.

The child’s rash is a milia-like diffuse homogeneous rash, with flushed skin between the rashes, insignificant swelling of the fingers (toes), and special signs such as perioral pale circles, pachyderm lines, and poplar tongue.

Penicillin therapy was effective.

Pharyngeal swab examination and bacterial culture can detect the pathogen.

Infectious mononucleosis

Similarities: fever, rash, enlarged lymph nodes.

Differences: infectious mononucleosis is characterized by the following.

No bulbar conjunctival congestion, no oral mucosal changes, and no sclerosis and desquamation of the ends of the extremities.

Routine blood tests show that peripheral blood leukocytes are dominated by monocytes, accounting for 70% to 90%, and abnormal lymphocytes up to 10%.

Septicemia

Similarities: fever, rash.

Differences: septicemia has a history of localized infection. Systemic symptoms are predominant. Young children are prone to convulsions, and in severe cases, confusion, delirium, and coma may occur. Positive blood culture may suggest the diagnosis of the disease.

Treatment

The mainstay of treatment is pharmacologic, including intravenous immunoglobulin (IVIG) and oral aspirin.

Medication

Intravenous immunoglobulin (IVIG)

The most important and effective treatment.

Applied as early as possible in the early stages of the disease (up to 10 days), it rapidly reduces fever and prevents the development of coronary artery disease.

In some children who do not respond to IVIG treatment (IVIG-naïve Kawasaki disease), it can be repeated once, or shock therapy with glucocorticoids can be chosen.

Those treated with IVIG should not be vaccinated with live attenuated vaccines such as measles, mumps, rubella and varicella vaccines for 11 months, as they are likely to interfere with the immune response to live virus vaccines, and should not be vaccinated with other vaccines for 6 months.

Aspirin

Early use in combination with IVIG may reduce fever and coronary artery lesions.

In the acute phase, it must be used in high doses to fight inflammation; after the fever subsides, it can be used in low doses to reduce platelet aggregation and prevent thrombosis.

The total course of treatment should be at least 12 weeks.

In case of coronary artery lesions, the duration of administration should be extended until the coronary artery lesions return to normal.

Glucocorticoids

Early use of glucocorticosteroids, in combination with aspirin and dipyridamole, may be considered in children who are refractory to IVIG therapy or who are at high risk of IVIG resistance.

Commonly used drugs: methylprednisolone, prednisone and so on.

Glucocorticosteroids can be gradually reduced and discontinued after 2-4 weeks of administration.

Some studies have shown that glucocorticosteroids can promote thrombosis and increase the risk of coronary artery disease and coronary aneurysm, and should not be used alone.

Others

In addition to aspirin, dipyridamole may be added if platelets are significantly elevated.

In combination with severe coronary artery disease and thrombocytosis, aspirin in combination with clopidogrel may be chosen; if coronary thrombosis is formed, warfarin may be added.

Surgery

Severe coronary artery lesions such as multiple coronary artery stenosis and ischemia require coronary artery bypass grafting if necessary.

Giant coronary aneurysm leading to thrombosis or severe narrowing of the lumen, surgical intervention can be considered when conditions are favorable in the post-disease period.

Other treatments

Symptomatic and supportive therapies are given according to the condition, such as fluid supplementation, myocardial protection drugs, liver protection therapy, control of heart failure, correction of arrhythmia, etc. Thrombolytic therapy is needed in time when there is myocardial infarction.

Prognosis

Most patients can return to normal after receiving timely treatment, while a small number of patients may develop coronary artery damage.

Cure

Kawasaki disease is a self-limiting disease with a favorable prognosis and a recurrence rate of 1% to 2%.

The long-term prognosis of Kawasaki disease depends on the involvement of the coronary arteries.

Coronary artery disease occurs in 25% to 30% of children without effective treatment and should be followed closely over time.

Coronary artery dilatation or mild-to-moderate coronary aneurysm mostly disappears within 2 years after the disease, but it is often left with functional abnormalities such as wall thickening and reduced elasticity.

Huge coronary artery aneurysm is not easy to disappear completely, which may lead to thrombosis or lumen narrowing.

Hazards

Myocardial infarction and rupture of coronary artery aneurysm may occur, posing a threat to life.

Those with coronary artery vascular injury may have long-term persistent coronary artery injury.

Daily

Patients need to eat more lean meat, eggs and milk, which can help recovery. Avoid strenuous exercise during the recovery period, gradually increase exercise after healing, follow the doctor’s instructions for review, and the doctor will focus on whether there is heart damage.

Daily life

Skin, oral and eye care

Attention should be paid to the child’s mouth and skin care to avoid secondary skin damage or infection.

Encourage the child to gargle after meals and apply lip balm or liquid paraffin to dry and cracked areas.

Trim nails in time to avoid scratching the affected area.

Keep the bed sheet clean and dry, intimate clothing should be soft and comfortable, preferably cotton products, if contaminated, change in time to prevent infection.

Keep eyes clean, use saline eye drops or eye ointment.

Dietary management

Eat light and easy-to-digest food, avoid spicy, stimulating, cold, hard and hot food.

Eat small and frequent meals, pay attention to the variety of food types and nutritional balance.

Eat more food rich in high quality protein, such as eggs, milk, lean meat, fish and shrimp, soybean products.

Eat more fresh fruits and vegetables.

Pay attention to replenish enough water, ensure the daily intake of milk, specific can follow the doctor’s advice.

For breastfeeding children, mothers should eat more protein-rich food to ensure the quality of breast milk.

Life management

Open the windows for ventilation 2-3 times a day, use air sterilizer to purify the air in the room, and keep the temperature and humidity of the sick room suitable.

Live a regular life, pay attention to rest and avoid staying up late.

Follow-up examination

For those without coronary artery lesions, a comprehensive examination will be conducted at the 1st month, 3rd month, 6th month and 1~2 years after discharge from the hospital, and the specific follow-up will follow the doctor’s instructions.

Physical examination, electrocardiogram and echocardiogram may be performed at the follow-up visit.

For giant coronary aneurysms, echocardiograms must be performed weekly within 45 days of the onset of the disease and monthly thereafter.

Prevention

Since the cause and pathogenesis of the disease are unknown, there is no effective prevention method for the time being.

It is recommended to improve the body’s immunity through diet, sleep and exercise in daily life to prevent the disease.