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.

An angiogram showing abnormal coronary arteries in a child suffering from Kawasaki's disease. The coronary arteries bulge into balloon shapes, called aneurysms, along their lengths.

(Photograph by Mehau Kulyk. Photo Researchers, Inc.)

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 http://sss.state.sd.us/doh/Pubs/Kawasaki.htm (accessed December 29, 2004).

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