Introduction
Background
Kawasaki disease is an acute febrile illness associated with multiorgan vasculitis of unknown etiology that primarily affects infants and children. The disease probably has existed for a long time, but it was not recognized as a separate entity until Dr Tomisaku Kawasaki first described it in 1967. Kawasaki disease was later reported in the English-language literature in 1974.
Pathophysiology
Kawasaki syndrome is characterized by fever; rash; swelling of the feet and hands; irritation; redness of the whites of the eyes; swollen lymph glands in the neck; and irritation and inflammation of the mouth, lips, and throat. The histologic changes of Kawasaki disease are consistent with a systemic vasculitis affecting medium and small arteries (and the veins to a lesser extent), with inflammatory lesions in all organs.
Frequency
United States
The annual incidence in the US is approximately 6-11 cases per 100,000 in children younger than 5 years. The peak incidence is in those aged 18-24 months. About 80% of the cases of Kawasaki disease have been reported in patients younger than 5 years.
International
Kawasaki disease has been reported throughout the world and predominantly affects children younger than 5 years. A slightly increased prevalence is seen in late winter and spring.
Mortality/Morbidity
- The mortality rate was more than 1% in the 1970s and decreased to less than 0.4% in the 1990s.
- In Japan and the US, Kawasaki disease is a leading cause of acquired heart disease in children. The heart may be affected in as many as 20% of children who develop Kawasaki disease. Kawasaki disease damages the coronary arteries (resulting in aneurysms) and myocardial muscles.
- Most deaths from Kawasaki disease result from acute-phase coronary disease or cardiac complications.
Race
Depending on the region, the average annual incidence varies from 9 cases per 100,000 population in the US to 108 cases per 100,000 children in Japan. A recurrence rate of 3-5% has been reported in Japan.
Sex
Japanese surveys of Kawasaki disease have documented a total of 848 patients as of 1992, with a male-to-female ratio of 1.3-1.5:1.
Age
In the US, 80% of the cases of Kawasaki disease manifest by the time the patient is aged 5 years.
Anatomy
The disease is multisystemic and may involve any organ.
Presentation
Etiology
The etiology of Kawasaki disease is unknown. Kawasaki disease does not appear to be hereditary or contagious. Because the illness frequently occurs in outbreaks, an infectious agent is the likely cause. Standard laboratory studies have been unsuccessful in identifying a specific agent. Although the initiating agent has not been identified yet, immune-system activation has been documented in the acute stage. Various secreted cytokines may target the vascular endothelial cells, producing cell-surface neoantigens. Antibodies produced against these antigens may target the vascular endothelium, resulting in a cascade of events that result in vascular damage.
Clinical manifestation
Kawasaki disease manifests as an acute febrile illness that can be delineated into acute, subacute, and convalescent phases. The acute phase lasts 7-14 days, the subacute phase extends from days 10-24, and the convalescent stage typically lasts 6-8 weeks.
Clinical criteria for diagnosis
The Japan Kawasaki Disease Research Committee and subsequently the American Heart Association have developed clinical criteria for this disease. The criteria for a diagnosis of Kawasaki disease are shown below.
- A fever that lasts for a minimum of 5 days
- The presence of 4 of the following 5 conditions:
- Bilateral conjunctival injection
- Changes of the mucosae of the oropharynx, including an injected pharynx, an injected and/or dry fissured lips, and a strawberry tongue
- Changes of the peripheral extremities, such as edema and/or erythema of hands and/or feet, and desquamation (usually beginning periungually)
- Rash (primarily truncal), which is polymorphous but nonvesicular
- Cervical lymphadenopathy
- Illness not explained by other known disease processes
Additional findings
Additional findings not included in the major diagnostic criteria are often present in patients with Kawasaki disease. These are subdivided into cardiac, noncardiac, and laboratory findings.
Cardiovascular manifestations can be prominent in the acute phase of the illness and are the leading cause of morbidity and mortality. Pancarditis may occur. Coronary aneurysms are believed to occur in 20-25% of children with Kawasaki disease. Involvement of the left coronary artery is more common than involvement of the right coronary artery. Patients with giant aneurysms (internal diameter of at least 8 mm) have the worst prognosis and are at greatest risk of developing thrombosis, stenosis, and myocardial infarction. Long-term follow-up studies demonstrate the resolution of coronary aneurysms within 5-18 months in approximately 50% of patients. Other cardiac manifestations of Kawasaki disease include myocarditis, pericarditis with pericardial effusions, wall-motion abnormalities, valvulitis or papillary muscle dysfunction, and acute mitral regurgitation secondary to rupture of the cordae tendineae.
Regarding noncardiac findings, Kawasaki disease is a multiorgan disease. During the acute phase, children may develop aseptic meningitis, hyperemic tympanic membrane, or uveitis. Neurologic complications, which include facial nerve palsy, seizures, and ataxia cerebral infarctions, are rare. Other common features include diarrhea, vomiting, abdominal pain, and pneumonitis. Gallbladder hydrops (acute acalculous distention of the gallbladder) may occur in the first 2 weeks of illness, it may be the result of the extension of periportal inflammation to the cystic duct, and it is typically self-limited. Arthritis and arthralgia are common in the acute phase. Findings that include erythema and induration at the site of recent Bacille Calmette-Guérin vaccination, testicular swelling, and peripheral gangrene also have been reported in patients with this disease.
In terms of laboratory findings, leukocytosis with left shift is common in the acute phase. Marked hypercoagulability, an elevated erythrocyte sedimentation rate, elevated liver transaminase levels, and sterile pyuria are also seen.
The ECG is usually normal.
The number of reports of atypical Kawasaki disease is increasing. In these cases, the criteria are not fulfilled, and yet, children develop coronary artery abnormalities. Intravenous (IV) gamma globulin is often administered to patients in whom Kawasaki disease is strongly suspected on the basis of the clinical findings.
Preferred Examination
In the absence of a specific diagnostic test, Kawasaki disease is a clinical diagnosis based on characteristic features of the history and on physical findings.
Differential Diagnoses
Other Problems to Be Considered
Measles
Scarlet fever
Drug reactions
Other viral exanthems
Toxic shock syndrome
Rocky Mountain spotted fever
Staphylococcal scalded arthritis
Leptospirosis
Mercury poisoning
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References
AHA. Diagnostic guidelines for Kawasaki disease. American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease. Am J Dis Child. Nov 1990;144(11):1218-9. [Medline].
Bolz D, Arbenz U, Fanconi S. Myocarditis and coronary dilatation in the 1st week of life: neonatal incomplete Kawasaki disease?. Eur J Pediatr. Jul 1998;157(7):589-91. [Medline].
Fujiwara M, Yamada TN, Ono Y. Magnetic resonance imaging of old myocardial infarction in young patients with a history of Kawasaki disease. Clin Cardiol. 2001;24:247-52. [Medline].
Japan Kawasaki Disease Research Committee. Diagnostic guideline of Kawasaki disease. Tokyo:. Japan Kawasaki Disease Research Committee;1984.
Kato H, Ichinose E, Yoshioka F. Fate of coronary aneurysms in Kawasaki disease: serial coronary angiography and long-term follow-up study. Am J Cardiol. May 1982;49(7):1758-66. [Medline].
Kawasaki T. [Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children]. Arerugi. Mar 1967;16(3):178-222. [Medline].
Kawasaki T, Kosaki F, Okawa S. A new infantile acute febrile mucocutaneous lymph node syndrome (MLNS) prevailing in Japan. Pediatrics. Sep 1974;54(3):271-6. [Medline].
Leung DY. Kawasaki disease. Curr Opin Rheumatol. Jan 1993;5(1):41-50. [Medline].
Nakamura Y, Yanagawa H, Kato H. Mortality rates for patients with a history of Kawasaki disease in Japan. Kawasaki Disease Follow-up Group. J Pediatr. Jan 1996;128(1):75-81. [Medline].
Newburger JW, Takahashi M, Burns JC. The treatment of Kawasaki syndrome with intravenous gamma globulin. N Engl J Med. Aug 7 1986;315(6):341-7. [Medline].
Rauch AM. Kawasaki syndrome: critical review of U.S. epidemiology. Prog Clin Biol Res. 1987;250:33-44. [Medline].
Schulman ST, Bass JL, Bierman F, et al. Management of Kawasaki syndrome: a consensus statement prepared by North American participants of the Third International Kawasaki Disease Symposium, Tokyo, Japan, December, 1988. Pediatr Infect Dis J. Oct 1989;8(10):663-7. [Medline].
Shulman ST, De Inocencio J, Hirsch R. Kawasaki disease. Pediatr Clin North Am. Oct 1995;42(5):1205-22. [Medline].
Yanagawa H, Yashiro M, Nakamura Y. Results of 12 nationwide epidemiological incidence surveys of Kawasaki disease in Japan. Arch Pediatr Adolesc Med. Jul 1995;149(7):779-83. [Medline].
Further Reading
Keywords
mucocutaneous lymph node syndrome, Kawasaki syndrome, multiorgan vasculitis
