Kawasaki disease

Kawasaki disease is a primary vasculitis affecting medium-sized vessels (including coronary arteries) with concurrent inflammation of the mucous membranes. Clinically, it is characterized by a febrile presentation and a polymorphic exanthem, possibly accompanied by non-specific signs. Its main complication arises from coronary issues during the convalescent phase.

It is rare but the second most common vasculitis in children (after Henoch-Schönlein purpura) and the most common in those under 5 years old. Its prevalence varies significantly between ethnic groups (highest incidence in Japan) but occurs across all continents.

Its etiology is unknown (the role of infectious agents on a genetically predisposed background is suspected).

Clinical Presentation

The disease typically progresses through three phases:

• Acute Phase
  • Lasts ~10 days
  • Fever > 40°C with inflammatory syndrome
  • Polymorphic exanthem (mimicking scarlet fever, measles, erythema multiforme, etc.)
  • Other possible symptoms: non-purulent conjunctivitis, enanthem of lips and tongue, indurated edema of hands/feet, cervical lymphadenopathy (large and firm, present in <50%), gastrointestinal symptoms, possible irritability in infants, potential lymphocytic meningitis
  • No ischemic signs, but tachycardia, gallop rhythm, and signs of congestion are possible
  • On echocardiography, coronary walls may appear hyperechogenic
• Subacute Phase
  • Begins after day 10 and lasts ~1 week
  • The exanthem progresses to desquamation
  • Fever and inflammation decrease
  • Possible appearance of arthritis or simple arthralgia
  • Complementary exams may show coronary dilation
• Convalescent Phase
  • Can last several weeks
  • Asymptomatic if no coronary lesions are present
  • If coronary dilation begins, coronary aneurysms may develop
    • Occur in 20-40% of cases (more common in children under 6 months) without preventive treatment
    • Risk of thrombosis and myocardial infarction
    • Risk of stenotic scarring, although vessel caliber most often returns to normal (however, long-term risks regarding endothelial function remain unclear)
  • In very young children, aneurysms may form on limb or abdominal arteries (especially mesenteric, with potential for mesenteric infarction). Renal or carotid involvement is rare.

Diagnosis

Clinical Diagnostic Criteria:

• Fever > 40°C lasting > 5 days, resistant to antibiotics and antipyretics
• + 4 criteria from the following:
  • In the first 3 days:
    • Non-purulent conjunctivitis
    • Painful, non-purulent cervical lymphadenopathy > 1.5 cm
    • Cheilitis with "strawberry tongue" and cracked lips
  • After 3 days:
    • Maculopapular polymorphic erythema beginning on the hands and feet, spreading to the trunk and groin folds
    • Edema of the hands and feet with desquamation 2-3 weeks later

Limitations of Criteria

Pauci-symptomatic forms are common, especially in infants… in such cases, diagnosis may only be made when late complications (coronary aneurysms!) occur. Given the severity of potential complications if untreated, treatment should not be delayed in cases of reasonable suspicion of Kawasaki disease.

Therapeutic Management - Treatments

Acute Phase Treatment

• IVIg 2g/kg over 1 to 2 days
• Aspirin (ASA) 80-100 mg/kg/day
  • Reduces the risk of coronary aneurysms by 3-4x if administered between day 6 and day 10 after fever onset. It is also often effective on symptoms. Doses can be repeated if there is no clinical or biological response.
  • If 2 doses are ineffective, consider exchange transfusion or plasmapheresis.
• !!!! Corticosteroids are classically contraindicated (they may increase the risk of aneurysms)… their use in refractory and recurrent cases beyond 3 weeks must be carefully considered!

Screening, Monitoring, and Treatment of Coronary Lesions

Monitoring in a pediatric cardiac unit:

• From the acute phase: weekly echocardiograms for 6 weeks
  • If normal: 1 follow-up echo at 6 months
    • If normal: stop follow-ups
  • If minor signs (hyperechogenicity/dilation), continue echo monitoring + aspirin treatment + control coronary angiography 6 months after resolution of inflammatory syndrome
  • If coronary aneurysm is detected: hospitalization + heparin therapy followed by vitamin K antagonists + daily ECG (monitor for ischemic signs?) + regular echocardiograms (monitor for localized myocardial dyskinesia?) +- thallium myocardial scintigraphy +- stress echo
    • In case of myocardial ischemia: early coronary angiography, evaluate conservative management vs medical treatment vs PTCA +- stent/bypass
    • Otherwise: coronary angiography, persantine thallium test or stress echo 6 months after resolution of inflammatory syndrome.

Bibliography

EMC, traité de médecine AKOS, Elsevier, 2018

Jameson JL et al., Harrison's Principles of Internal Medicine, 20th edition, McGraw Hill Higher Education, 2018