Kawasaki syndrome

Definition

Kawasaki syndrome is a potentially fatal inflammatory disease that affects several organ systems in the body, including the heart, circulatory system, mucous membranes, skin, and immune system. As of 2004 its cause was unknown.

Description

In the 1960s, Tomisaku Kawasaki noted a characteristic cluster of symptoms in Japanese schoolchildren. Ultimately named for Kawasaki, the disorder was subsequently found worldwide. Kawasaki syndrome, also called mucocutaneous lymph node syndrome (MLNS), is an inflammatory disorder with potentially fatal complications affecting the heart and its larger arteries.

Demographics

Kawasaki syndrome occurs primarily in infants and children; about 80 percent of diagnosed patients are under the age of five. On rare occasions, the disorder has been diagnosed in teenagers or adults. Nearly twice as many males are affected as females. Although persons of Asian descent are affected more frequently than either black or white individuals, there does not appear to be a distinctive geographic pattern of occurrence. Although the disease usually appears in individuals, it sometimes affects several members of the same family and occasionally occurs in small epidemics. About 3,000 cases are diagnosed annually in the United States.

Causes and symptoms

The specific cause of Kawasaki syndrome was as of 2004 unknown, although the disease resembles an infectious illness in many ways. It has been suggested that Kawasaki syndrome represents an allergic reaction or other unusual response to certain types of infections. Some researchers think that the syndrome may be caused by the interaction of an immune cell, called the T cell, with certain poisons (toxins) secreted by bacteria.

Kawasaki syndrome has an abrupt onset, with fever as high as 104°F (40°C) and a rash that spreads over the patient's chest and genital area. The fever is followed by a characteristic peeling of the skin beginning at the fingertips and toenails. In addition to the body rash, the patient's lips become very red, with the tongue developing a "strawberry" appearance. The palms, soles, and mucous membranes that line the eyelids and cover the exposed portion of the eyeball (conjuntivae) become purplish-red and swollen. The lymph nodes in the patient's neck may also become swollen. These symptoms may last from two weeks to three months, with relapses in some patients.

In addition to the major symptoms, about 30 percent of patients develop joint pain or arthritis, usually in the large joints of the body. Others develop pneumonia , diarrhea , dry or cracked lips, jaundice , or an inflammation of the membranes covering the brain and spinal cord (meningitis ). A few patients develop symptoms of inflammation in the liver (hepatitis), gallbladder, lungs, or tonsils.

About 20 percent of patients with Kawasaki syndrome develop complications of the cardiovascular system. These complications include inflammation of the heart tissue (myocarditis), disturbances in heartbeat rhythm (arrhythmias), and areas of blood vessel dilation (aneurysms) in the coronary arteries. Other patients may develop inflammation of an artery (arteritis) in their arms or legs. Complications of the heart or arteries begin to develop around the tenth day after the illness begins, when the fever and rash begin to subside. A few patients may develop gangrene (the death of soft tissue) in their hands and feet. The specific causes of these complications were as of 2004 not known.

Diagnosis

Because Kawasaki syndrome is primarily a disease of infants and young children, the disease is most likely to be diagnosed by a pediatrician. The physician will first consider the possible involvement of other diseases that cause fever and skin rashes , including scarlet fever , measles , Rocky Mountain spotted fever , toxoplasmosis (a disease carried by cats), juvenile rheumatoid arthritis, and a blistering and inflammation of the skin caused by reactions to certain medications (Stevens-Johnson syndrome).

Once other diseases have been ruled out, the patient's symptoms will be compared with a set of diagnostic criteria. The patient must have a fever lasting five days or longer that does not respond to antibiotics , together with four of the following five symptoms:

• inflammation of the conjunctivae of both eyes with no discharge
• at least one of the following changes in the mucous membranes of the mouth and throat: "strawberry" tongue, cracked lips, or swollen throat tissues
• at least one of the following changes in the hands or feet: swelling caused by excess fluid in the tissues, peeling of the skin, or abnormal redness of the skin
• a skin eruption or rash associated with fever (exanthem) on the patient's trunk
• swelling of the lymph nodes in the neck to a size greater than 1.5 cm

Given the unknown cause of this syndrome, there are no laboratory tests that can confirm the diagnosis. The following test results, however, are associated with the disease:

• Blood tests show a high white blood cell count, high platelet count , a high level of protein in the blood serum, and mild anemia.
• A chest x ray may show enlargement of the heart (cardiomegaly).
• Urine may show the presence of pus or an abnormally high level of protein.
• An electrocardiogram may show changes in the heartbeat rhythm.

In addition to these tests, it is important to take a series of echocardiograms during the course of the illness because 20 percent of Kawasaki patients develop coronary aneurysms or arteritis that will not appear during the first examination.

Treatment

Kawasaki syndrome is usually treated with a combination of aspirin, to control the patient's fever and skin inflammation, and high doses of intravenous immune globulin to reduce the possibility of coronary artery complications. Some patients with heart complications may be treated with drugs that reduce blood clotting or may receive corrective surgery.

Follow-up care includes two to three months of monitoring with chest x rays , electrocardiography, and echocardiography. Treatment with aspirin is often continued for several months.

Prognosis

Most patients with Kawasaki syndrome will recover completely, but about 1–2 percent die as a result of blood clots forming in the coronary arteries or as a result of a heart attack. Deaths are sudden and unpredictable. Almost 95 percent of fatalities occur within six months of infection, but some have been reported as long as 10 years afterward. Long-term follow-up of patients with aneurysms indicates that about half show some healing of the aneurysm. The remaining half has a high risk of heart complications in later life.

Parental concerns

It is important that parents of children diagnosed with Kawasaki syndrome follow recommended treatments and follow-up care for the disease, because of the risk of potentially serious complications. Any worsening or unexplained new symptoms should be reported to the treating pediatrician.

KEY TERMS

Aneurysm —A weakened area in the wall of a blood vessel which causes an outpouching or bulge. Aneurysms may be fatal if these weak areas burst, resulting in uncontrollable bleeding.

Arrhythmia —Any deviation from a normal heart beat.

Arteritis —Inflammation of an artery.

Cardiomegaly —An enlarged heart.

Conjunctiva —Plural, conjunctivae. The mucous membrane that covers the white part of the eyes (sclera) and lines the eyelids.

Exanthem —A skin eruption associated with a disease, usually one accompanied by fever as in Kawasaki syndrome.

Gangrene —Decay or death of body tissue because the blood supply is cut off. Tissues that have died in this way must be surgically removed.

Hepatitis —An inflammation of the liver, with accompanying liver cell damage or cell death, caused most frequently by viral infection, but also by certain drugs, chemicals, or poisons. May be either acute (of limited duration) or chronic (continuing). Symptoms include jaundice, nausea, vomiting, loss of appetite, tenderness in the right upper abdomen, aching muscles, and joint pain. In severe cases, liver failure may result.

Meningitis —An infection or inflammation of the membranes that cover the brain and spinal cord. It is usually caused by bacteria or a virus.

Mucocutaneous lymph node syndrome (MLNS) —Another name for Kawasaki syndrome. The name comes from the key symptoms of the disease, which involve the mucous membranes of the mouth and throat, the skin, and the lymph nodes. MLNS is a potentially fatal inflammatory disease of unknown cause.

Myocarditis —Inflammation of the heart muscle (myocardium).

Stevens-Johnson syndrome —A severe inflammatory skin eruption that occurs as a result of an allergic reaction or respiratory infection.

T cell —A type of white blood cell that is produced in the bone marrow and matured in the thymus gland. It helps to regulate the immune system's response to infections or malignancy.

Resources

BOOKS

Rowland, Anne. "Bacteria: Diseases of Possible Infectious or Unknown Etiology." In Principles and Practice of Pediatric Infectious Diseases, 2nd ed. Edited by Sarah S. Long et al. St. Louis, MO: Elsevier, 2003.

Rowley, Anne H., and Stanford T. Shulman. "Kawasaki Disease." In Nelson Textbook of Pediatrics. Edited by Richard E. Behrman et al. Philadelphia: Saunders, 2004.

WEB SITES

"Kawasaki Syndrome (mucocutaneous lymph node syndrome)." South Dakota Department of Health, November 18, 2004. Available online at <sss.state.sd.us/doh/Pubs/Kawasaki.htm> (accessed December 29, 2004).

Rebecca J. Frey, PhD Rosalyn Carson-DeWitt, MD

Kawasaki Syndrome

Definition

Kawasaki syndrome is a potentially fatal inflammatory disease that affects several organ systems in the body, including the heart, circulatory system, mucous membranes, skin, and immune system. It occurs primarily in infants and children but has also been identified in adults as old as 34 years. Its cause is unknown.

Description

Kawasaki syndrome, also called mucocutaneous lymph node syndrome (MLNS), is an inflammatory disorder with potentially fatal complications affecting the heart and its larger arteries. Nearly twice as many males are affected as females. Although persons of Asian descent are affected more frequently than either black or white individuals, there does not appear to be a distinctive geographic pattern of occurrence. Eighty percent of cases involve children under the age of four. Although the disease usually appears in individuals, it sometimes affects several members of the same family and occasionally occurs in small epidemics.

Causes and symptoms

The specific cause of Kawasaki syndrome is unknown, although the disease resembles infectious illnesses in many ways. It has been suggested that Kawasaki syndrome represents an allergic reaction or other unusual response to certain types of infections. Some researchers think that the syndrome may be caused by the interaction of an immune cell, called the T cell, with certain poisons (toxins) secreted by bacteria.

Kawasaki syndrome has an abrupt onset, with fever as high as 104°F (40°C) and a rash that spreads over the patient's chest and genital area. The fever is followed by a characteristic peeling of the skin beginning at the fingertips and toenails. In addition to the body rash, the patient's lips become very red, with the tongue developing a "strawberry" appearance. The palms, soles, and mucous membranes that line the eyelids and cover the exposed portion of the eyeball (conjuntivae) become purplish-red and swollen. The lymph nodes in the patient's neck may also become swollen. These symptoms may last from two weeks to three months, with relapses in some patients.

In addition to the major symptoms, about 30% of patients develop joint pains or arthritis, usually in the large joints of the body. Others develop pneumonia, diarrhea, dry or cracked lips, jaundice, or an inflammation of the membranes covering the brain and spinal cord (meningitis ). A few patients develop symptoms of inflammation in the liver (hepatitis), gallbladder, lungs, or tonsils.

About 20% of patients with Kawasaki syndrome develop complications of the cardiovascular system. These complications include inflammation of the heart tissue (myocarditis ), disturbances in heartbeat rhythm (arrhythmias ), and areas of blood vessel dilation (aneurysms) in the coronary arteries. Other patients may develop inflammation of an artery (arteritis) in their arms or legs. Complications of the heart or arteries begin to develop around the tenth day after the illness begins, when the fever and rash begin to subside. A few patients may develop gangrene, or the death of soft tissue, in their hands and feet. The specific causes of these complications are not yet known.

Diagnosis

Because Kawasaki syndrome is primarily a disease of infants and young children, the disease is most likely to be diagnosed by a pediatrician. The physician will first consider the possible involvement of other diseases that cause fever and skin rashes, including scarlet fever, measles, Rocky Mountain spotted fever, toxoplasmosis (a disease carried by cats), juvenile rheumatoid arthritis, and a blistering and inflammation of the skin caused by reactions to certain medications (Stevens-Johnson syndrome).

Once other diseases have been ruled out, the patient's symptoms will be compared with a set of diagnostic criteria. The patient must have a fever lasting five days or longer that does not respond to antibiotics, together with four of the following five symptoms:

• Inflammation of the conjunctivae of both eyes with no discharge
• At least one of the following changes in the mucous membranes of the mouth and throat: "strawberry" tongue; cracked lips; or swollen throat tissues
• At least one of the following changes in the hands or feet: swelling caused by excess fluid in the tissues; peeling of the skin; or abnormal redness of the skin
• A skin eruption or rash associated with fever (exanthem) on the patient's trunk
• Swelling of the lymph nodes in the neck to a size greater than 1.5 cm.

Since the cause of Kawasaki syndrome is unknown, there are no laboratory tests that can confirm the diagnosis. The following test results, however, are associated with the disease:

• Blood tests show a high white blood cell count, high platelet count, a high level of protein in the blood serum, and mild anemia
• Chest x ray may show enlargement of the heart (cardiomegaly)
• Urine may show the presence of pus or an abnormally high level of protein
• An electrocardiogram may show changes in the heartbeat rhythm

In addition to these tests, it is important to take a series of echocardiograms during the course of the illness because 20% of Kawasaki patients will develop coronary aneurysms or arteritis that will not appear during the first examination.

Treatment

Kawasaki syndrome is usually treated with a combination of aspirin, to control the patient's fever and skin inflammation, and high doses of intravenous immune globulin to reduce the possibility of coronary artery complications. Some patients with heart complications may be treated with drugs that reduce blood clotting or may receive corrective surgery.

Follow-up care includes two to three months of monitoring with chest x rays, electrocardiography, and echocardiography. Treatment with aspirin is often continued for several months.

Prognosis

Most patients with Kawasaki syndrome will recover completely, but about 1-2% will die as a result of blood clots forming in the coronary arteries or as a result of a heart attack. Deaths are sudden and unpredictable. Almost 95% of fatalities occur within six months of infection, but some have been reported as long as 10 years afterward. Long-term follow-up of patients with aneurysms indicates that about half show some healing of the aneurysm. The remaining half has a high risk of heart complications in later life.

Resources

BOOKS

Shandera, Wayne X., and Maria E. Carlini. "Infectious Diseases: Viral & Rickettsial." In Current Medical Diagnosis and Treatment, 1998, edited by Stephen McPhee, et al., 37th ed. Stamford: Appleton & Lange, 1997.

KEY TERMS

Aneurysm— Dilation of an artery caused by thinning and weakening of the vessel wall.

Arrythmia— Abnormal heart rhythm.

Arteritis— Inflammation of an artery.

Cardiomegaly— An enlarged heart.

Conjunctivae— The mucous membranes that cover the exposed area of the eyeball and line the inner surface of the eyelids.

Exanthem— A skin eruption associated with a disease, usually one accompanied by fever as in Kawasaki syndrome.

Gangrene— The death of soft tissue in a part of the body, usually caused by obstructed circulation.

Hepatitis— Inflammation of the liver.

Meningitis— Inflammation of the membranes, called the meninges, covering the brain and spinal cord.

Mucocutaneous lymph node syndrome (MLNS)— Mucocutaneous lymph node syndrome, another name for Kawasaki syndrome. The name comes from the key symptoms of the disease, which involve the mucous membranes of the mouth and throat, the skin, and the lymph nodes.

Myocarditis— Inflammation of the heart muscle.

Stevens-Johnson syndrome— A severe inflammatory skin eruption that occurs as a result of an allergic reaction or respiratory infection.

T cell— A type of white blood cell that develops in the thymus gland and helps to regulate the immune system's response to infections or malignancy.

Kawasaki disease (mucocutaneous lymph node syndrome) (kah-wă-sah-ki) n. a condition of unknown cause affecting young children, usually less than five years old, and characterized by fever, conjunctivitis, a sore throat, and a generalized rash and reddening of the palms and soles. This is followed by peeling of the fingers and toes. The fever usually persists for 1–2 weeks. Approximately one-fifth of children develop myocarditis and aneurysms of the coronary arteries. Treatment involves aspirin therapy, and gammaglobulin has recently been shown to reduce the risk of coronary artery disease. [ T. Kawasaki (20th century), Japanese physician]

Kawasaki Disease

What Is Kawasaki Disease?

How Common Is It?

Is It Contagious?

What Are the Signs and Symptoms of the Disease?

Making the Diagnosis

How Do Doctors Treat Kawasaki Disease?

What Are the Possible Complications of Kawasaki Disease?

Can Kawasaki Disease Be Prevented?

Resources

Kawasaki disease is an inflammatory illness in children that involves the body’s blood vessels. The hallmarks of the disease are high fever, swollen glands, and a rash, and it may lead to complications affecting the heart.

KEYWORDS

for searching the Internet and other reference sources

Coronary aneurysm

Coronary artery

Gamma globulin

Heart attack

Heart disease

Myocardial infarction

Myocarditis

What Is Kawasaki Disease?

For children in the United States, Kawasaki disease is the leading cause of acquired heart disease, that is, heart disease that is not present at birth but develops later in life. In 1967, the Japanese pediatrician Tomisaku Kawasaki first described the illness. He called it mucocutaneous (myoo-ko-kyoo-TAY-nee-us) lymph node syndrome, but today, it is better known as Kawasaki disease. Even after many years of research, the cause of this disease remains unknown, but doctors suspect that an infectious microorganism* may trigger the onset of inflammation in the body. Kawasaki disease sometimes occurs in outbreaks, often in late winter or spring, and can resemble diseases like measles or scarlet fever*, which suggests a possible link to an infectious organism.

*microorganism

is a tiny organism that can be seen only using a microscope. Types of microorganisms include fungi, bacteria, and viruses.

*scarlet fever

is an infection that causes a sore throat and a rash.

Kawasaki disease can cause inflammation of blood vessels, mucous membranes (moist linings of the mouth, nose, eyes, and throat), lymph nodes*, and the heart. Although it eventually clears up on its own, if left untreated it can damage the blood vessels that supply the heart muscle. Kawasaki disease is associated with a 1 in 5 risk of coronary aneurysms*. This blood vessel damage can lead to a heart attack, especially in very young children.

*lymph

(LIMF) nodes are small, bean-shaped masses of tissue that contain immune system cells that fight harmful microorganisms. Lymph nodes may swell during infections.

*coronary aneurysm

(KOR-uh-nair-e AN-yuh-rih-zum) is an abnormal stretching and weakening of a blood vessel that supplies blood to the heart. If it breaks open, it may cause serious damage to the heart, sometimes leading to death.

How Common Is It?

As many as 3,500 children are hospitalized with Kawasaki disease each year in the United States. Four out of five children who get the disease are less than 5 years old, and it is extremely rare in children older than 15. Kawasaki disease develops in boys about twice as often as in girls. It is more common in children of Asian descent, though it occurs in all races.

Is It Contagious?

The disease itself has not been proved to be contagious. Doctors suspect, however, that an infectious microorganism may trigger it and that the organism might be contagious. Nonetheless, it is rare for more than one child in a family to have Kawasaki disease.

What Are the Signs and Symptoms of the Disease?

Kawasaki disease has distinctive features. A high fever, often more than 104 degrees Fahrenheit, usually appears first and lasts for at least 5 days. Afterward, signs of Kawasaki disease show up in stages and may include a red rash over the entire body, cracked lips, inflamed lining of the mouth, and a red, swollen tongue. Infected children also may have reddened and swollen hands, feet, fingers, and toes, with peeling skin; conjunctivitis in both eyes; sore, stiff joints; and swollen lymph nodes in the neck. Some children experience abdominal pain and diarrhea as well. The earliest phase of the disease, including fever and rash, usually lasts 10 to 14 days. The later phase, with peeling skin and slowly easing joint pain, can persist up to 2 months. Heart problems, if they occur, are more likely to show up during this time.

Making the Diagnosis

No single laboratory test can identify Kawasaki disease, so doctors make the diagnosis based on the child’s symptoms and a physical examination: 5 days of high fever, accompanied by most of the associated telltale signs mentioned earlier. Blood tests help support the diagnosis and include tests to determine the numbers of white blood cells (cells that respond to infection) and platelets* and tests that detect inflammation in the body. Echocardiograms* and chest X rays are done to look for evidence of damage to the heart and coronary arteries*.

*platelets

(PLATE-lets) are tiny disk-shaped particles within the blood that play an important role in clotting (the body’s way of thickening blood to stop bleeding).

*echocardiogram

(eh-ko-KAR-dee-uh-gram) is a diagnostic test that uses sound waves to produce images of the heart’s chambers and valves and blood flow through the heart.

*coronary arteries

(KOR-uh-nair-e AR-tuh-reez) are the blood vessels that directly supply blood to the heart.

How Do Doctors Treat Kawasaki Disease?

Kawasaki disease is treated in the hospital. Children typically are given high doses of aspirin to decrease inflammation, prevent blood clots* in the heart’s blood vessels, and lessen fever and joint pain. A one-time dose of intravenous gamma globulin* also is given to lower the risk of heart problems, particularly coronary aneurysms. (Even though aspirin is an important part of the treatment for Kawasaki disease, children normally are not given aspirin for minor fever or pain, because Reye syndrome*, a dangerous condition, has been linked to aspirin use in children.)

*blood clots

are thickenings of the blood into a jelly-like substance that helps stop bleeding. Clotting of the blood within a blood vessel can lead to blockage of blood flow.

*gamma globulin

(GAH-muh GLAH-byoo-lin) is a type of protein in the blood that contains the antibodies produced by the cells of the body’s immune system that help defend the body against infection-causing germs, such as bacteria and viruses.

*Reye syndrome

(RYE SIN-drome) is a rare condition that involves inflammation of the liver and brain, and sometimes appears after illnesses such as chicken pox or influenza. It has also been associated with taking aspirin during certain viral infections.

Much of the treatment for Kawasaki disease focuses on keeping the patient comfortable while the illness runs its course. After the disease clears up, children still need follow-up testing to make sure it has not caused heart disease. They may have additional echocardiograms or angiograms* to examine the heart for damage and sometimes a stress test* to check the heart’s function.

*angiogram

(AN-jee-o-gram) is a test in which X rays are taken as dye is injected into the body, showing the flow of blood through the heart and blood vessels.

*stress test

measures the health of a person’s heart while the heart is intentionally stressed by exercise or medication.

What Are the Possible Complications of Kawasaki Disease?

Up to 25 percent of children with untreated Kawasaki disease may experience complications that involve the heart and coronary arteries. With treatment, that risk goes down to less than 5 percent. Babies younger than 1 year and children older than 9 years have the greatest risk of heart problems. By far the most serious complication of Kawasaki disease is coronary aneurysm. If an aneurysm clots or, more rarely, bursts in a blood vessel supplying the heart muscle, it can cause a heart attack or even death. Kawasaki disease can affect the heart in other ways as well, leading to myocarditis* or an irregular heartbeat.

*myocarditis

(my-oh-kar-DYE-tis) is an inflammation of the muscular walls of the heart.

Can Kawasaki Disease Be Prevented?

Because little is known about its cause, there are no proven ways to prevent Kawasaki disease.

See also

Conjunctivitis

Myocarditis/Pericarditis

Resources

Organizations

American Heart Association, National Center, 7272 Greenville Avenue, Dallas, TX 75231. The American Heart Association provides information about Kawasaki disease and related heart problems at its website.

Telephone 800-242-8721 http://www.americanheart.org

U.S. National Library of Medicine, 8600 Rockville Pike, Bethesda, MD 20894. The National Library of Medicine’s website provides general information for the public on a variety of health topics, including Kawasaki disease.

Telephone 888-346-3656 http://www.nlm.nih.gov