A 35-year-old male applies for life insurance. He was diagnosed at age 3 with Kawasaki Disease and was later told that several coronary aneurysms had been detected by echocardiography.
Unfortunately, old records were not available, and he reported that no follow up was performed since childhood. He has remained completely asymptomatic for more than 30 years, but within the year prior to application he complained of chest pain. He underwent a treadmill exercise test, achieving 14, METS which was negative for chest pain, ST depression or arrhythmia.
What is Kawasaki Disease (KD) and what are the prognostic implications of associated coronary aneurysms?
Kawasaki Disease, also known as muco-cutaneous lymph node syndrome, is an acute systemic vasculitis of small and medium-sized arteries that predominantly affects patients younger than five years.
It is usually a self-limited condition with fever and other acute inflammatory manifestations lasting for an average of 12 days if not treated. The vasculitis of KD can be complicated by cardiac disorders and especially coronary aneurysms which occur in 25 to 30% of cases if not treated.
KD represents the most prominent cause of acquired coronary artery disease in childhood in industrialized countries and can lead to a coronary artery disease at adult age. The cause of Kawasaki Disease is unknown. Because the illness frequently occurs in outbreaks, an infectious disease such as a virus and/or the body’s response to this infection combined with genetic factors may cause the disease.
Named after Dr. Tomisaku Kawasaki, a Japanese pediatrician, the disease has probably been in existence for a long time but was not recognized as a separate entity until 1967.
Children of all races and ethnic groups can develop KD, but its annual incidence is higher in Asian populations and in Japan in particular (112/100,000) compared to the United States (19/100,000) and the UK (8.1/100,000)
Approximately 75% to 80% of cases in the US occur in children younger than 5 five years of age; the median age is 1.5 years, and the male to female ratio is 1.5. In 2004, the American Heart Association (AHA) published diagnostic criteria for classical (typical) and incomplete (atypical) KD.
KD is a clinical diagnosis (Table 1). There is no specific diagnostic test, although laboratory and echocardiographic findings may be helpful in evaluating and differentiating KD from other conditions. Coronary abnormalities such as aneurysms may develop within the first week to 10 days of disease onset, making early diagnosis and treatment essential. The natural and typical course of KD is favorable most of the time in absence of coronary complications, and the symptoms usually resolve within 4 to 6 weeks.
Table 1 – Clinical Criteria for diagnosing Kawasaki Disease
|Fever for 5 days with no other cause||100% (required)|
|Plus 4 of the following: |
|Oral findings: red lips or mucosa, cracked lips, "strawberry tongue"||96% - 97%|
|Conjunctivitis or conjunctival injection (non-purulent)||89%|
|Hands with red palms or feet with red soles, edema acutely, later desquamation||75% - 76%|
|Cervical lymphadenopathy, >1.5 cm, often unilateral||62% - 63%|
Complications in KD primarily result from cardiovascular involvement and include coronary artery (CA) aneurysms (Figure 1), depressed myocardial contractility and heart failure, myocardial infarction, arrhythmias and peripheral arterial occlusion. Non-cardiac complications are generally uncommon, but may include shock and multiple organ dysfunction syndrome, macrophage activation syndrome, altered renal function, acute abdominal catastrophes, and sensorineural hearing loss.
Figure 1 – Coronary aneurysms due to Kawasaki Disease
The risk of developing coronary aneurysms is greater for children who are younger than age six months and when fever lasts more than two weeks. These aneurysms regress within two years in 60% of the cases. However, aneurysm dimensions greater than 4 mm are predictive of a high likelihood of intimal and medial thickening in the future, which can lead to CAD.
The recommended initial therapy includes intravenous immune globulin (IVIG) and aspirin. The effectiveness of IVIG therapy is best established for patients treated within the first 7 to 10 days of illness. There are few data on the efficacy of IVIG therapy administered more than 10 days after the onset of KD in preventing CA aneurysms
Long-term morbidity of KD is primarily related to the degree of CA involvement. Recurrence of KD is uncommon.
The reported mortality rate of all cases of KD is low (0.1% to 0.3%). The rare fatal outcomes from severe cardiac involvement in KD are generally the result of either myocardial infarction or arrhythmias, although aneurysm rupture can also occur.
Long-term morbidity for patients following KD depends upon the severity of CA involvement (Table 2).
- Children without cardiovascular abnormalities detected in the acute and subacute phase (up to eight weeks after onset of disease) appear to be clinically asymptomatic 10 to 21 years later.
- CA dilatation <8 mm generally regresses over time, and most aneurysms <6 mm in diameter fully resolve by echocardiogram.
- Patients with giant aneurysms (GA) (maximum diameter ≥8 mm) are at the greatest risk for myocardial infarction resulting from CA occlusion.
Table 2 - Classification of Risk Based on CA Findings
|Risk Level||Description||Suggested Follow-up|
|I||No CA changes at any time||CV assessment every 5 years|
|II||Transient ectasia of CA, resolves within 8 weeks||CV assessments every 3-5 years|
|III||One small to medium CA aneurysm||Annual cardiology follow-up with periodic imaging & ECG|
|IV||>1 aneurysm 8+ mm or multiple or complex aneurysms without obstruction||Cardiology follow-up twice per year imaging or angiography as needed|
|V||CA obstruction||Cardiology follow-up twice per year with imaging or angiography as needed|
Adapted from Newburger et. al.
In the world’s largest cohort of patients with KD complicated by GA who have been followed up for the longest time, Suda et. al. have shown a survival rate of 88% up to 30 years (Figure 2), with a 59% cumulative intervention rate at 25 years after the onset of KD.
Figure 2 – Kaplan-Meier survival curve of those with GA up to 30 years after the diagnosis of KD
Returning to the Case
From the history, the proposed insured fits in Risk Category IV or V. Several studies indicate that ongoing remodeling of coronary arteries affected by KD might continue long after the initial infection, leading to the development of coronary stenosis years after the onset of the disease.
The proposed insured has not done the recommended follow up until he developed chest pain. Furthermore, the treadmill exercise test is the least sensitive method to detect myocardial ischemia in these patients. In our case, it appears prudent to postpone and offer to reconsider after a more sensitive and specific CAD test and CA imaging, such as Magnetic Resonance Angiography, Computed Tomographic Angiography or stress echocardiography with attention to the coronary arteries.
- Baker AL, et al. “Kawasaki Disease” Circulation.2008; 118:e110-e112
- Saguil A, et al. “Diagnosis and Management of Kawasaki Disease” Am Fam Physician.2015; 91(6): 365-371
- Cimaz R, et al. “La maladie de Kawasaki” Rev Prat 2007; 57: 1985-1988
- Uehara R, et al. “Epidemiology of Kawasaki Disease in Asia, Europe, and the United States” J Epidemiol 2012; 22 (2): 79-85
- Inokuchi R, et al. “Coronary Artery Aneurysms After Adult-Onset Kawasaki Disease” Circulation. 2013; 127: 1636-1637
- Sensaki H, “Long-Term Outcome of Kawasaki Disease” Circulation. 2008; 118: 2763-2772
- Suda K, et al. “Long-Term Prognosis of Patients with Kawasaki Disease Complicated by Giant Coronary Aneurysms: A Single-Institution Experience” Circulation.2011; 123: 1836-1842
- Carlton-Conway D, et al.”Behaviour sequelae following acute Kawasaki Disease” BMC Pediatr. 2005;5(1):14.
- UpToDate – Kawasaki Disease, last accessed 08/08/2016
- Newburger J, et al. “Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease A Statement for Health Professionals from the Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association” Circulation. 2004;110:2747-2771.