For epidemiology of Kawasaki disease, please see Chapter 148.

The pathologic basis of this syndrome is an acute nonspecific and systemic vasculitis. Cardiovascular lesions of this syndrome are classified into four stages according to the duration of illness. Stage I (days 0 to 12) is characterized by acute vasculitis of the microvessels and small arteries and by acute perivasculitis and endarteritis of the major arteries, especially of the coronary system. Stage II (days 12 to 25) is characterized by panvasculitis and aneurysm formation of the coronary arteries, resulting in embolus formation and local obstruction. In stage III (days 26 to 40), granulation of the medium-sized arteries and the disappearance of inflammation in the microvessels and smaller
arteries are evident. In stage IV (day 40 and beyond), scarring, thickening of the intima, calcification, embolus formation, and recanalization are seen. Arteritis is particularly severe and frequently affects the coronary and iliac arteries, but major arterial branches of the aorta, such as mesenteric, renal, celiac, subclavian, carotid, and hepatic arteries, also are sites of involvement. Interstitial myocarditis, pericarditis, inflammation of the sinoatrial and atrioventricular conduction system, endocarditis, and valvulitis also occur.

The clinical manifestations include prolonged fever, conjunctival injection without exudate, reddening of the lips and oral mucosa, and reddening and indurative edema of the palms and soles in the initial stage, followed by membranous desquamation of the fingertips in the convalescent stage, polymorphous exanthem, and cervical nonpurulent lymphadenopathy.

The similarities of the clinical features and pathologic findings in Kawasaki disease to those in infantile polyarteritis nodosa have been confirmed by investigators.

The most serious complications of Kawasaki disease are cardiovascular, and they usually occur in the second week of illness. Auscultation of the heart reveals a gallop rhythm and distant heart sound in 80% of the patients, usually in the second week of illness. Rarely, a murmur of mitral regurgitation is heard. Cardiomegaly is revealed on chest roentgenography for more than 30% of the patients. Electrocardiographic (ECG) changes are common findings and include low-voltage and ST-segment depression in the first week of illness and PR prolongation, QTc prolongation, and ST-segment elevation during the second and third weeks. Arrhythmias are rare occurrences and are temporary. Development of paroxysmal supraventricular tachycardia, atrial fibrillation, ventricular tachycardia, or complete atrioventricular block is associated with serious coronary arterial lesions. ECG changes are common occurrences in patients with cardiomegaly, congestive heart failure, and heart murmur.

Dilatations or aneurysms of the coronary arteries caused by vasculitis are recognized in approximately 50% of the patients who have not received intravenous immunoglobulin (IVIG) therapy beginning on days 7 or 8 of the illness. The left coronary artery is involved more commonly than is the right, and the proximal parts of the left or right coronary arteries are involved frequently. More distal parts of the coronary arteries are involved occasionally. The dilatations or aneurysms remain even after the acute phase in 10% to 20% of these patients. With the widespread use of IVIG, however, coronary artery lesions now occur in 10% to 15% percent of patients, yet 1% develop giant aneurysms greater than 8 mm in diameter.

According to Kato and colleagues, of 128 patients who had documented coronary aneurysms during the acute phase, angiographic findings became normal in 73 (57%) within 1 to 2 years, a finding suggesting regression of the aneurysms in 1 to 2 years after the acute illness. A giant coronary aneurysm with a diameter of 8 mm or more and saccular, sausage-shaped, or multiple aneurysms are considered to be important risk factors in the progression to stenosis or occlusion. Ischemic heart disease may develop in fewer than 3% of the patients.

The patients with the following clinical symptoms and signs are more likely to develop coronary artery involvement:

For the early prediction of coronary involvement in the acute phase, elevated plasma thromboglobulin levels and hypoalbuminemia have been reported to be sensitive indicators for differentiating patients with coronary aneurysms from those with normal coronary arteries. No absolute criteria accurately predict which patient will develop coronary arterial lesions. Although an uncommon occurrence, an aneurysm or dilatation can develop in the more distal part of the coronary arteries, and the normal echocardiographic appearance of the proximal right or left coronary arteries may not exclude coronary lesions completely. Most patients with coronary artery lesions have normal ECGs, chest roentgenograms, and auscultatory findings.

Pericarditis, usually with a small amount of pericardial effusion, occurs in approximately 30% of the patients in the first to second week of illness. It rarely progresses to cardiac tamponade, and usually special treatment is not needed. Mitral regurgitation caused by valvulitis or ischemia of the papillary muscle is observed in approximately 1% of the patients in the acute phase. It usually is mild and improves, but in rare cases, congestive heart failure develops and requires digitalis, diuretics, and vasodilators. Aortic regurgitation and pulmonary regurgitation caused by valvulitis occur infrequently.

Myocardial infarction caused by thromboembolic occlusion of aneurysms or progression of the stenotic lesions accounts for most deaths caused by Kawasaki disease. An analysis of 104 deaths in Japan showed that 60 patients (57%) died of acute myocardial infarction and 7 patients (9%) died of congestive heart failure and myocardial infarction. Infarction developed within 1 year of the onset of the disease in 73% of the cases complicated by myocardial infarction and within 3 months in 40% of those cases. Asymptomatic myocardial infarction also is a common occurrence.