How Common is Recurrent Kawasaki Disease?

Patient Presentation
A 3.5-year-old female came to clinic with a 2-day history fever up to 101°F. The evening before she had complained of a sore throat but had no rhinorrhea, cough or rash. She was drinking reasonably well and was urinating frequently. She had been to a birthday party where an older child had had strep throat. The past medical history was positive for Kawasaki Disease diagnosed at 17 months of age and treated with intravenous immunoglobulin (IVIG) on day 6 of fever. Her echocardiograms had been negative and she was being appropriately monitored by cardiology. The family history was positive for heart disease and hypertension in grandparents in the 70s. The review of systems was otherwise negative.

The pertinent physical exam showed a preschooler who was febrile to 39.3°C, heart rate of 104 beats/minute, and respiratory rate of 24. Capillary refill was brisk and her mucous membranes were moist. She had palatal petechiae but no exudates in her throat. She had a few shotty anterior cervical and inguinal nodes that were all < 0.5 cm and freely mobile. Her ears were normal. Cardiac examination showed no murmurs with normal S1 and S2. Her abdominal and lung examination were negative and her skin examination showed no rashes.

The diagnosis of possible strep throat was made. The laboratory evaluation of a rapid strep test confirmed the diagnosis and the parents were educated regarding giving her the penicillin and reasons to call if she was not improving. “Oh we’ll call all right. After her having Kawasaki Disease we’re probably always a little worried about any fever and it coming back. We know that it’s rare to begin with and even less likely to come back, but yet we know it can. I’m not glad she’s sick but glad it is something that we know what it is and can treat it,” her father explained.

Kawasaki Disease (KD) was first described in 1967 by Dr. Tomisaku Kawasaki, and since has been identified world-wide. It is an acute, self-limited, febrile illness seen usually in children < 5 years. In North America the incidence is ~25/100,000 children < 5 years. Highest prevalence is seen in Asian children, particularly those of Japanese ancestry. Males are more common than females (~1.5:1). In Japan, case fatality rate is < 0.1%.

The cause is not identified although strong data suggests an interaction between infectious agents and genetic susceptibility. KD is a clinical diagnosis as is recurrent KD. Without treatment at the initial episode, 15-25% of pediatric KD patients may develop cardiac aneurysms but this is decreased to 4% with IVIG treatment. It is the most common reason for acquired heart disease in developed countries.

Treatment for KD changed in 2004, and was updated by the American Heart Association in 2017 (See To Learn More for review).
Primary treatment for initial KD is IVIG (2 mg/kg x 1 infusion) within 10 days of symptoms onset but may be given later also. Aspirin can also be given until the patient is afebrile (moderate dose = 30-50 mg/kg/day to high dose = 80 mg/kg/day). Corticosteroids are sometimes used if patients do not respond to initial therapy.

KD is defined as:

  • Fever of at least 5 days (often > 39-40°C, can last 1-3 weeks without treatment)
  • Plus 4 or more principal clinical features following:
    • Changes in lips and oral cavity – erythema, cracked lips, strawberry tongue, diffuse injection
    • Bilateral bulbar conjunctival injection without exudate
    • Polymorphous exantham – maculopapular, diffuse erythroderma or erythema multiforme-like
    • Cervical lymphadenopathy – more than 1.5 cm, usually unilateral, and in the anterior cervical triangle but may be in other locations

    Note: Patients with 4 or more of the 5 principal features, especially extremity changes, can have the diagnosis made on day 4 of fever.

Laboratory findings associated with KD include:

    During acute phase

    • Leukocytosis with neutrophilia and immature forms
    • Elevated C-reactive protein
    • Elevated erythrocyte sedimentation rate
    • May also be present: sterile pyuria, hyponatremia and hypoalbuminemia

    During 2nd week after fever onset

    • Thrombocytosis

Evaluation for other possible diseases with clinical findings includes:

  • Viral infections – especially adenovirus, enterovirus, Epstein-Barr virus and measles
  • Scarlet fever
  • Staphylococcal scalded skin syndrome
  • Toxic Shock Syndrome
  • Bacterial cervical lymphadenitis
  • Drug hypersensitivity reactions
  • Stevens-Johnson syndrome
  • Juvenile rheumatoid arthritis, systemic onset
  • Rocky Mountain spotted fever
  • Leptospirosis

Learning Point
Recurrent KD is rare with the incidence rate basically unchanging over the last 30 years in Japan. Overall the incidence rate for patients reviewed between 2003-2012 in Japan, was 3.89 /1000 person-years. The authors also note that all deaths in the cohort (N=17) occurred in nonrecurrent KD patients. Risk factors in this study were age < 3 years, male gender and being resistant to initial IVIG therapy. Cardiac problems during the initial event was not a risk factor. Other studies have found other risk factors but these vary by study.

Overall, recurrent KD occurs in ~2-3% of all patients who developed initial KD. Recurrent KD is even rarer in adult patients with a 4th case being described in 2016 in a 23-year-old male who had initial KD at age 4 years.

Questions for Further Discussion
1. What is the clinical definition of incomplete KD and its treatment?
2. What are indications for a cardiology consultation?

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