Kawasaki Disease Diagnostic Test Development: Addressing a Critical Unmet Need in Paediatrics

Kawasaki disease (KD), a form of systemic vasculitis in young children that can lead to coronary artery aneurysms, remains a challenging condition to diagnose. As highlighted in a recent presentation by Daniëlle van Keulen of SkylineDx at the COG Europe meeting in Milan, timely diagnosis and treatment of KD is critical to reducing risk of complications. However, the median time to diagnosis is around 6-7 days, with up to 1 in 6 KD patients diagnosed after 10 days. This delay is concerning given that IVIG treatment is most effective when started early in the disease course.

The classical patient pathway involves multiple days of observation and testing to rule out other causes before KD may be considered. SkylineDx aims to shorten this pathway by developing a gene expression diagnostic test called KiDs-GEP. Their approach demonstrates the potential of omics technologies to transform disease diagnosis. After initial discovery, they successfully bridged the 196-gene classifier from microarray to a more user-friendly qPCR assay. A retrospective verification study on samples from Rady Children’s Hospital showed strong discrimination of KD from febrile controls.

Developing this test involves addressing many challenges. Epidemiologic data on KD is limited, with variable incidence estimates globally. There is no single specialist who manages KD, so engagement with multiple groups is needed. Understanding exact differential diagnoses and incomplete KD frequency was difficult given lack of objective diagnostic criteria. Thoughtful study design was also critical given lack of suitable biobanks and gold standard diagnosis, issues common when studying paediatric diseases.

To overcome these hurdles, SkylineDx leveraged key collaborations, including with Dr. Jane Burns, renowned KD expert at University of California San Diego. Ongoing engagement with specialists worldwide has been invaluable for product development. Participation in an EU-funded consortium, DIAMONDS, will support further validation and access to samples.

In summary, developing omics-based diagnostics for complex paediatric conditions requires extensive multidisciplinary engagement. While challenging, success in this area can dramatically improve patient outcomes, as envisioned with the new KiDs-GEP test for KD. SkylineDx's efforts exemplify the immense potential of personalized medicine to solve unmet needs.