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Essentials of Kawasaki Disease

An article from the e-journal of the ESC Council for Cardiology Practice

The Kawasaki disease (KD) is a childhood vasculitis affecting mainly coronary arteries in the form of aneurysm or stenosis. The disease occurs worldwide, but Asians are at highest risk. Males and young children are mostly affected. Imaging techniques like echo, multi-slice CT, SPECT and MRI can be of value for diagnosis and patient follow-up. Management of KD includes intravenous immunoglobulin (IVIG) and aspirin. Catheter interventions for acute coronary syndromes can be used, but care should be taken to the new aneurysm formation due to balloon angioplasty.



Description

KD presents as an acute febrile illness of >5 days with rash, conjunctivitis, lympadenopathy, geographical clustering suggestive of infectious disease, desquamation of palms and soles, arthritis, jaundice and irritability. On clinical examination there is a hyperdynamic precordium, tachycardia, gallop rhythm, flow murmur due to anemia, pansystolic murmur due to mitral regurgitation, low contractility due to myocarditis and occasionally low cardiac output or shock. The ECG presents arrhythmia, prolonged PR, nonspecific ST and T waves. Usually CRP is >3.0 mg/DL and ESR >40 mm/h. 

The subacute phase occurs 2-4 weeks after the onset of symptoms and is characterised by periungual desquamation with thrombosis and development of coronary artery aneurysms. The convalescent phase occurs eight weeks after the onset of the disease. During this phase, symptoms resolve.

KD affects mainly the coronary arteries

KD affects mainly the coronary arteries. Coronary artery aneurysms occur in 25% of cases, if treatment is not given early. Aneurysms may also occur in celiac, mesenteric, femoral, renal and other arteries. During the acute phase, the endothelial and smooth-muscle cells present an inflammatory infiltration of the vessel wall with neutrophils, which are then replaced by macrophages, lymphocytes and plasma cells. During this process, the vessel loses its integrity and is weakened. This process results in aneurysm formation. Later during the course of the disease, fibrotic or stenotic lesions develop. Slow blood flow within aneurysms predisposes to thrombus formation. Risk factors for developing aneurysms include male gender, age younger than 1 year or older than 5 years, persistent fever refractory to treatment, anemia, hypoalbuminemia and a high level of C-reactive protein on presentation (1).  

The majority of coronary artery aneurysms (CAA) resolve spontaneously

Usually the majority of coronary artery aneurysms (CAA) resolve spontaneously 1-2 years after the onset of KD. Thus, approximately half of the children with CAAs during the acute phase of the disease have normal-appearing vessels by angiography 1-2 years later. Smaller aneurysms are more likely to regress than larger ones (1). Other variables associated with greater likelihood of regression include age under 1 year at onset of KD, fusiform versus saccular morphology and location of the CAA in the distal part of coronary artery.

Unresolved CAAs persist and develop stenotic lesions and/or thrombus. Rarely, a CAA may rupture within the first few months after onset of the disease. Myocardial infarction due either to thrombosis of an aneurysm or to stenotic lesion is the main cause of death in KD.

The risk of infarction is highest during the first year after the onset of the disease. KD also causes abnormal lipid metabolism that persists beyond clinical resolution of the disease. 

Long-term management of KD

Long-term management of KD is determined by the risk of myocardial infarction. The revised AHA guidelines help in risk stratification of patients based on expert consensus opinion (1). This approach has 5 risk levels.

  1. No coronary artery changes
  2. Transient coronary artery changes that disappear in six to eight weeks
  3. Small or medium aneurysms in a major coronary artery
  4. One or more giant aneurysms or multiple or complex aneurysms in the same coronary artery
  5. Coronary artery obstruction

Consequently, serial evaluation of size and location of CAAs is necessary for treatment decision. The disease presents a challenge for the clinician, because the development of aneurysms is clinically silent in most cases and may be recognized many years later after the diagnosis, only due to late complications such as myocardial infarction or sudden death.

Imaging techniques can contribute both to the diagnosis and to the follow-up of KD

Echocardiography is the first choice technique for fast, accurate diagnosis and follow-up of aneurysms, but it is deficient in adolescence, due to poor acoustic window at this age. Multislice computed tomography (MSCT) provided clear visualization of coronary artery aneurysm and coronary calcifications but has not yet progressed to image accurately stenotic lesions. The high radiation dose, an inherent CT problem, makes the technique particularly inappropriate for children follow-up. Single-photon emission computed tomography (SPECT) is the current way to evaluate myocardial perfusion. Compared with treadmill test, SPECT is more sensitive than treadmill electrocardiographic exercise test for the detection of coronary artery abnormalities, but the specificity of treadmill exercise is better than 201Tl scintigraphy, which is also a radiating technique. X-Ray coronary angiography (CA) is the classic method for coronary arteries evaluation, but it is an invasive and radiating technique irrelevant for follow-up.

Treatment

Catheter interventions for acute coronary syndromes can be an effective treatment. However, care should be taken to the new aneurysm formation due to balloon angioplasty.

Noninvasive coronary magnetic resonance angiography (MRA) has been successfully used in the diagnosis of Kawasaki disease (2). It has the advantage of being noninvasive and nonradiating. Although the incidence of pediatric disease is low (2-3%), the mortality rate due to myocardial infarction is 22% after the first infarction and 66 and 87% after the second and third infarctions, respectively. In this context, gadolinium-enhanced MRI (Gd-enMRI) is the gold standard for scar detection due to myocardial infarction. The technique is also able to diagnose subendocardial infarctions missed by SPECT. Gd-DTPA has actually been used for myocardial infarction detection in patients with Kawasaki syndrome. Thus MRI can offer the possibility of an integrated evaluation consisting of coronary angiography, left ventricular function, viability and inflammation assessment (3, 4).

Management of KD includes intravenous immunoglobulin (IVIG) and aspirin

When given during the acute phase, IVIG reduces the prevalence of CAA (28). According to current recommendations a single dose of 2 g/kg should be given within 10 days of symptoms onset. Giving IVIG before day 5 of disease onset does not prevent cardiac complications (1).

After 10 days of illness, only children with continued inflammation in the presence of persistent fever or coronary aneurysm need IVIG therapy. A small percentage of KD will develop CAA despite treatment (1). High-dose aspirin (80 to 100 mg/kg/day) is also recommended for initial treatment. However, unlike IVIG, aspirin does not prevent long-term development of CAA (5). Patients with aneurysms should take anticoagulation with warfarin or a combination of antiplatelet and anticoagulation therapy. In case of infarction both streptokinase and tissue plasminogen administration is recommended (1). Angioplasty, or by-pass grafting can also be used in specific cases.    

 The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.

References


Vol5 N°16

Notes to editor


Address for correspondence:
Sophie Mavrogeni, MD FESC
Nucleus Member of the ESC WG for Cardiovasular Magnetic Resonance
50 Esperou Street,
175-61 P.Faliro,
Athens, Greece.
Tel/Fax: +30-210-98.82.797
e-mail: soma@aias.gr

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.