Epidemiologic studies on Kawasaki disease during 30 years in Sweden

<p dir="ltr">Kawasaki disease (KD) is a paediatric vasculitis that presents with fever, affecting mostly medium-sized arteries. Inflammation is visible in the skin, eyes, mouth, and lymph nodes, while other organs such as the gastrointestinal tract and the nervous system can also be involved. KD develops dependent on genetic susceptibility in combination with certain, yet unknown triggers. Untreated, it leads to coronary artery aneurysms (CAA) in a quarter of affected children with a risk for myocardial infarction in the acute or chronic phase.</p><p dir="ltr">Incidence rates are significantly higher in Asian populations than elsewhere in the world. For the Nordic population, the last comprehensive study of KD at a national level was performed in 2013. The overall aim of this thesis was therefore to characterize the epidemiologic features of KD in a Nordic population over a long period of time from different perspectives. With data from the Swedish national healthcare registers, we developed a dataset to study KD over 32 years in the Swedish population. We found that the incidence rate of KD rose steadily prior to the SARS-CoV-2 pandemic, with certain peak years and an increasing percentage of children that are born outside Sweden themselves, or with parents born outside Sweden. We concluded that migration patterns may be associated with generally increasing numbers of KD.</p><p dir="ltr">As we used register data for KD with previously unvalidated diagnostic codes, we performed a validation study of the clinical diagnosis of KD based on the medical records. We found a 95% concordance between the registered KD diagnosis and the medical records in relation to international KD criteria. We thus concluded that the validity of a KD diagnosis in our national registers is high with high specificity. These data are therefore reliable both for studies of risk factors for KD and future epidemiological research. When examining clinical care data, we observed that treatment guidelines were followed, and that outcomes were usually favourable.</p><p dir="ltr">In our population, we also wanted to identify risk factors for KD. First, we performed a case-control study to investigate if a history of infection associated with a higher risk of developing KD. We found that children who later developed KD already have a higher rate of diagnoses of infections from birth than controls, not just directly before KD.</p><p dir="ltr">In a second case-control study, we investigated perinatal risk factors. We found that prematurity was a significant risk factor for developing KD. In addition, prenatal maternal smoking, advanced maternal age, and Asian or African descent were also found to be risk factors.</p><p dir="ltr">For the clinician, it is important to know the extent of CAA so that diagnostics and treatment are precise. As Sweden only has low numbers of children with CAA that underwent detailed imaging by cardiac catheterization, we developed a comparative study of the prevalence and morphology of CAA in a mixed European population. We found that distal CAAs were almost exclusively detected alongside proximal CAAs. Thus, distal CAA are not likely to be missed with standard diagnostic technique, helping to avoid unnecessary interventions.</p><p dir="ltr">In conclusion, this thesis adds to the current understanding of epidemiologic and clinical factors in Kawasaki disease.</p><h3>List of scientific papers</h3><p dir="ltr">I. Patterns of migration underlie changing epidemiology of Kawasaki disease outside of Covid-19: a cohort study. <b>Rudolph A,</b> Mofors J, Frisk A, Schiller B, Elinder G, Nordenstam F, Eliasson H, Bergman G, Granath F, Wahren-Herlenius M. [Submitted]</p><p dir="ltr">II. Clinical features and treatment of Kawasaki disease in validated cases in the Swedish National Patient Register. <b>Rudolph A,</b> Mofors J, Eliasson H, Bergman G, Wahren-Herlenius M. [Manuscript]</p><p dir="ltr">III. Associations of infection burden with Kawasaki disease in a population-based setting during 30 years. Mofors J, <b>Rudolph A,</b> Schiller B, Elinder G, Sonesson SE, Eliasson H, Bergman G, Wahren-Herlenius M. RMD Open 2025;11:e005160. <a href="https://doi.org/10.1136/rmdopen-2024-005160" rel="noreferrer" target="_blank">https://doi.org/10.1136/rmdopen-2024-005160</a></p><p dir="ltr">IV. Swedish nationwide study found that prematurity was associated with Kawasaki disease. Frisk A, <b>Rudolph A,</b> Eliasson H, Nordenstam F, Bergman G, Wahren-Herlenius M, Mofors J. Acta Paediatrica, 2025; 0:1-10. <a href="https://doi.org/10.1111/apa.70071" rel="noreferrer" target="_blank">https://doi.org/10.1111/apa.70071</a></p><p dir="ltr">V. Specific morphology of coronary artery aneurysms in mainly white patients with Kawasaki disease: Initial data from the cardiac catheterization in Kawasaki disease registry. Weisser J, Arnold L, Wällisch W, Quandt D, Opgen-Rhein B, Riede FT, Gräfe F, Michel J, Arnold R, Schneider H, Tanase D, Herberg U, Happel C, Tietje M, Tarusinov G, Grohmann J, Hummel J, <b>Rudolph A,</b> Haas N, Jakob A. J Am Heart Assoc. 2024;13:e034248. <a href="https://doi.org/10.1161/JAHA.124.034248" rel="noreferrer" target="_blank">https://doi.org/10.1161/JAHA.124.034248</a></p>