Kawasaki Disease
Pathophysiology
Kawasaki Disease (KD) is a rare childhood illness of generalized vasculitis. Inflammation can affect all types of blood vessels in the body; arteries, veins and capillaries. Cardiovascular complications, particularly coronary artery aneurysms, coronary occlusion, and cardiac ischemia can result in significant morbidity or even mortality. With treatment, however, KD most often resolves with few if any long term health issues.
The etiology of KD remains unknown. Clinical and epidemiological features strongly suggest an infectious cause, but no bacterial or viral cause has been identified to date. KD is not communicable and can not be prevented. It does occur more often in children of Asian and Pacific Island descent, and is more likely to affect boys than girls. The genetic basis of susceptibility is currently unknown. Most cases occur in children < 5 years of age, and it is only rarely seen in adults. The fact that it is not often seen in infants < 6 months old may suggest passive immunity from maternal antibodies. It is hypothesized that many children experience asymptomatic infections that lead to immunity as adults. It may be that only a small fraction of children develop overt clinical features of KD.
Diagnosis is typically based on symptomology. The first and main symptom of KD is a fever that lasts longer than 5 days. Fever will generally peak 39C-40C (102F-104F) and is not responsive to routine antipyretics. For this reason, the family practice doctor or pediatrician is often the first health professional to see the patient. The child may present with injected eyes, red lips, and erythema and induration on the palms and soles of the feet, which may be painful. All these are manifestations of the inflamed blood vessels in the acute stage of KD. There may be cervical lymphadenopathy present, and rashes on the trunk and genital area (rashes generally appear 5 days after onset of fever). The tongue may also be red and swollen (strawberry tongue). There may also be abdominal pain, nausea and vomiting. Generally, a diagnosis of KD will be made if there has been history of a fever longer than four days plus four of the previously cited symptoms. Rocky Mountain spotted fever, scarlet fever, and juvenile rheumatoid arthritis must be ruled out, but any suspicion of KD should be referred for treatment immediately. Early treatment is critical to averting long term complications.
Aneurysms may develop in other extraparenchymal muscular arteries, such as celiac, mesenteric, femoral, iliac, renal, axillary and brachial arteries. Close monitoring and follow up of these children is advised, as the active inflammation in the acute phase is replaced over several weeks to months by progressive fibrosis and scar formation.
Desquamation of the fingers and toes usually takes place two to three weeks after the onset of fever. This may extend to include the palms and soles of the feet. Approximately 1-2 months after the onset of fever, deep transverse grooves across the nails may appear (Beau’s lines).
Treatment
The pediatrician or family practice doctor may be the first to suspect Kawasaki Disease (KD). Referral for immediate treatment and evaluation by a pediatric cardiologist are key to best outcomes for the patient. The cardiologist will want to obtain a baseline echocardiogram, EKG and chest x-ray to assess cardiac function. These tests will be repeated typically in another 2 weeks, and then at 6 weeks. The cardiologist will follow the patient to monitor for arrhythmias, heart failure, valvular insufficiency or myocarditis. The length of follow up is determined by the severity of cardiac involvement from Kawasaki Disease.
The American Heart Association and the American Academy of Pediatrics recommend initial therapy of immune globulin (IVIG) and high dose aspirin therapy. Best results are obtained when therapy begins within 10 days of illness, but ideally should start by the 7th day of illness. Aspirin is used for both it’s anti-inflammatory and anti-platelet effects. Dosing for aspirin therapy is typically 30-50 mg/kg/day divided into four doses. Some hospital protocols will start as high as 100 mg/kg/day. After the child is afebrile for 48 hours, low dose aspirin therapy will begin (3-5 mg/kg/day). This will continue until laboratory markers of inflammation have returned to normal (platelet count, C-reactive Protein). Erythrocyte sedimentation rate (ESR) is not typically used as a measure of recovery, as it may continue to rise after administration of IVIG regardless of the amount of inflammation present. Aspirin therapy is typically complete at approximately two months following illness, unless there was indeed development of coronary artery aneurysm. In that case, length of treatment will vary according to the severity of the defect.
The mechanism of the beneficial effect of IVIG remains unknown. It appears to have a generalized anti-inflammatory effect, along with reduction of fever, CRP, and fibrinogen. IVIG 2 G/kg is administered intravenously over 8-12 hrs. The patient is observed for 12-24 hrs following IVIG administration to confirm resolution of fever. Without treatment, fever associated with Kawasaki Disease would persist for 12-14 days and risk of coronary aneurysm would remain high. Studies have shown that the combination of Aspirin therapy and IVIG together minimize the risk of coronary aneurysm development more than just aspirin therapy alone. In addition, echocardiographic data suggest that IVIG may more rapidly reverse depressed myocardial contractility associated with KD.
IVIG is a biologic product pooled from donor plasma that undergoes a number of processing and sterilizing procedures. There may be variable efficacy with different brands of IVIG. Despite it’s advantages, IVIG is expensive and potentially toxic. Significant hemolysis can occur within 5-10 days following infusion. As with any blood product, close monitoring and observation for untoward reactions is vitally important. The benefits for patients with KD far outweigh the risks.
It is extremely important not to dismiss fevers in children who have been treated for KD. Persistent or refractory fever is the single strongest risk factor for development of coronary aneurysm. Additional therapy may be indicated if the child does not fully respond to the initial treatment. Mis- or late diagnosis, or complete lack of IVIG treatment is associated with potentially fatal outcomes.
Follow up after discharge will include monitoring for recurrence of fever and repeat echocardiograms. Live virus vaccines are postponed for 11 months after IVIG administration, as passively acquired antibodies persist for approximately 11 months, and IVIG may interfere with vaccine immunogenicity. Schedules for other routine immunizations do not need to be altered. Influenza immunization is particularly important for children on long term aspirin therapy because of the possible risk of Reyes syndrome. These patients should receive inactivated influenza vaccine and varicella vaccine. Varicella should be repeated in 11 months.
Children recovering from KD generally do not feel “like themselves” but it is usually not necessary to formally limit their activity. They will tend to choose quieter activities and self impose rest periods. Encourage families to be patient, supportive and accepting of the recovery time these children will need.
References:
Kawasaki Disease. Retrieved from https://www.nhlbi.nih.gov/health-topics/kawasaki-disease.
Sundel, Robert. (2017). Kawasaki disease: Initial treatment and prognosis. UpToDate. Retrieved from https://www.uptodate.com/contents/kawasaki-disease-initial-treatment-and…
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