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PEDIATRICS INFORMATION - KAWASAKI DISEASE

By Beatriz Ara˙jo de Freitas
From Medstudents Homepage





Kawasaki disease is a febrile condition affecting primarily children who are 5 years of age or younger. It is notable for its association with vasculitis of the large coronary blood vessels. It has surpassed rheumatic fever as the leading cause of acquired heart disease in children in the United States, has been recognized worldwide, and appears to be increasing in frequency. Kawasaki disease has been described in all racial groups, but appears to be a predilection for Japanese.

There is no evidence for person-to-person transmission. The cause remains unknown, but bacterial toxins similar the staphylococcal toxins of the toxic shock syndrome may be involved in its pathogenesis. There is no evidence that autoimmunity plays a role in pathogenesis; the finding of increased members of T-cell subset is consistent with toxin superantigen stimulation.





CLINICAL MANIFESTATION

Diagnostic rests on the demonstration of characteristic clinical signs:

A. Fever lasting for at least 5 days unresponsive to antibiotic therapy.
B. Presence of four of the following conditions:
    1. Bilateral nonpurulente conjunctival injection.
    2. Changes of the mucosa of the oropharynx, including infected pharynx, infected and/or dry fissured lips, strawberry tongue.
    3. Changes of the peripheral extremities, such as edema and/or erythema of the hands or feet, desquamation, usually beginning periungually.
    4. Rash, primarily truncal, polymorphous but nonvesicular.
    5. Cervical lymphadenopathy.

C. Illness not explained by other known disease process.

The disease can be subdivided into four stages:

1. Acute Phase:
  • Lasts about 10 days.
  • Fever, conjunctivitis, oral changes, extremity changes, irritability, rash, cervical lymphadenopathy, high erythrocytes sedimentation rate.
  • Aseptic meningitis frequently is found.
  • Myocarditis and pericarditis may occur.
2. Subacute Phase:
  • Lasts from days 11 through 21.
  • Usually associated with a decrease in fever.
  • Irritability persists.
  • Normalization of most clinical findings.
  • Palpable aneurysms may develop.
3. Convalescent Phase:
  • Lasts from days 21 through 60.
  • Most clinical findings resolve.
  • Aneurysmal dilatation of peripheral vessels may persist.
  • Conjunctivitis may persist.
  • Myocardial infarctions and rupture of aneurysms may occur.
4. Chronic Phase:
  • After day 60.
  • Angina pectoris, coronary stenosis, or myocardial insufficiency may develop.
Atypical cases manifesting few early signs but later caricaturists coronary artery lesions have been reported. Atypical patients, often younger than 1 year of age, may have incorrect admitting diagnoses [gastroenteritis, viral syndrome, sepses], and a high morbidity rate.





LABORATORY FINDINGS

There are no diagnostic tests. Leukocytosis with a predominance of immature forms and thrombocytosis [in the 2nd-3rd week] can be streaking; anemia is also common. Sedimentation rates and C-reactive proteins levels are usually greatly elevated. Test results for autoantibodies including ANA and rheumatoid factors are negative, and hemolytic complement levels are normal or high. Mild proteinuria and pyuria may be present, as may cerebrospinal fluid pleocytosis. Serum levels of hepatic transaminases and bilirubin may be slightly elevated.

Cardiac involvement is the most important manifestation of the disease. Two-dimensional echocardiogram should be performed in all children with known or suspected Kawasaki disease at the time of presentation and again during the first 2 weeks of disease.





DIAGNOSIS

Diagnosis rests on the clinical features. There are no diagnostic laboratory tests, although demonstration of coronary artery involvement revealed by echocardiogram is highly suggestive of this condition. The differential diagnoses includes scarlet fever, toxic shock syndrome, leptospirosis, Epstein-Barr virus infection, juvenile rheumatoid arthritis, measles, acrodynia, Rocky Mountain spotted fever, drug reactions, Stevens-Johnson syndrome, and vasculitis syndromes.




PROGNOSIS

Recovery is usually complete in patients who do not have detectable coronary vasculitis; second attacks occur only rarely. A few reports detail the later occurrence of aneurysms of large vessels than the coronary arteries.

Duration of fever, presumably reflecting the severity of ongoing vasculitis, has been confirmed as a powerful predictor of these lesions.





TREATMENT

Kawasaki disease responds dramatically to therapy with intravenous gamma globulin given during the period of active febrile disease. Fever and other attendant systemic manifestations often abate within 24 hours of initial therapy. Furthermore, controlled studies show that intravenous gamma globulin therapy given early in disease prevents coronary vascular involvement. The recommended regimen consists of an intravenous infusion of 2 g/kg given as a single dose over 10-12 hours. Therapy given within 10 days of onset appears to be effective in preventing coronary vascular damage. Side effects of intravenous gamma globulin therapy are rare and include anaphylaxis, chills, fever, headache, and myalgia.

Salicylate therapy is also indicated during the febrile phase; therapeutic serum concentrations of 20 to 30 mg/dl are desirable but may be difficult to achieve, even with doses of salicylates as high as 100 mg/kg/24 hours. Continuance of low, single-dose [5 mg/kg/24 hours] salicylate therapy for its antithrombotic effects has been advocated for 6 to 8 weeks after the period of active disease subsides. Low-dose aspirin with or without dipyridamole should be continued until coronary lesions resolve.

Corticosteroids therapy is rarely used in Kawasaki disease, and some consider it contraindicated.

Thrombolytic therapy with agents such as streptokinase has been used for patients with thrombosis or peripheral artery ischemia. Arterial bypass surgery may be appropriate for rare patients with severe coronary occlusion.





REFERENCES

1. Nelson: Textbook of Pediatrics

2. Peter C. Rowe, Angela Quinlan and Brian K. H. Luke: Value of degenerative change in neutrophils as a diagnostic test for Kawasaki disease: J PEDIATR 1991: vol 119:370-374

3. Robert P. Sundel, Jane C. Burns, Annette Baker, Alexa Beiser and Jane W. Newburger: Gamma globulin re-treatment in Kawasaki disease: J PEDIAT 1993.vol 123:657-659







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