Etiology, course and long-term effects of Kawasaki disease

Kawasaki disease is an acute systemic vasculitis in childhood, in which
coronary artery aneurysms can develop as a complication. Kawasaki disease is
the leading cause of acquired heart disease in childhood.

Standard treatment consists of a single infusion of high dose intravenous
immunoglobulin (IVIG) and acetylsalicylic acid (aspirin). Coronary artery
aneurysms develop in more than 25% of untreated children. Studies have shown
that treatment with IVIG has reduced this risk to less than 10%. The majority
of patients recover quickly after the start of the IVIG treatment, but
approximately 15-20% of children do not respond to this standard treatment.
Children who are unresponsive to IVIG have an increased risk of developing
aneurysms.

Although Kawasaki disease was first described in 1967, the cause of the disease
is still unknown. Since no causative pathogen(s) have been found, it is not
clear which children are susceptible to Kawasaki disease. There is no test to
diagnose Kawasaki disease. Difference in incidences observed between different
ethnic populations and the results of twin studies, make it likely that the
genetic predisposition of the child also plays a role. The SARS-CoV2 pandemic
has proven that a prior infection can trigger Kawasaki disease, and can present
in some children with symptoms of shock, previously diagnosed as the so-called
Kawasaki disease shock syndrome.

Questions about the future of these patients are also important. Are only
children with coronary aneurysms at increased risk of cardiovascular diseases
in later life, or are unaffected children also at risk due to the prior
vasculitis? Previous studies are limited and often inconclusive.

The objective is to gain more insight in:
1. Possible causative agents of Kawasaki disease. At the moment no single
causative agent has been identified despite the strong suspicion of an
infectious etiology of the disease.
2. Genetic factors related to susceptibility and disease course of Kawasaki
disease.
3. Biomarkers to help diagnose Kawasaki disesae with increased certainty.
4. Influence of this pediatric vasculitis on long term cardiovascular outcome
measures.

Prospective, cross-sectional and (partly) longitudinal study

Additional blood and body fluids for microbial tests (microbiome analysis; DNA
analysis).

Another disadvantage of study participation is the traveling time for the
families to visit our multidisciplinary outpatient care unit at the AMC
(instead of the nearby hospital of admission) after the acute onset of disease.
During this standard visit the extra blood withdrawal for our study will be
combined with the standard blood tests.