Factors linked to Kawasaki disease and MIS-C in children with prolonged fever: A retrospective cohort study

Abstract

Background/Aim: Prolonged fever in children presents a diagnostic challenge due to its diverse underlying causes. While infectious diseases historically played a primary role, recent shifts in disease patterns and the emergence of conditions such as multisystem inflammatory syndrome in children (MIS-C) have added complexity. Understanding factors contributing to prolonged fever, particularly the rise in MIS-C and Kawasaki Disease (KD), is vital for accurate diagnosis and timely intervention. This study aimed to identify the etiologies causing prolonged fever in children with temperatures exceeding 38°C for a minimum of 5 days and to examine its relationship with conditions like MIS-C and KD following the coronavirus disease 2019 (COVID-19) pandemic. Methods: We conducted a retrospective cohort study at a pediatric hospital in Istanbul, Turkey, involving 243 children aged 3 months to 17 years with prolonged fever (>38°C for ≥5 days) between April 2020 and October 2022. We collected data on patient demographics, clinical characteristics, laboratory results, and final diagnoses. The study categorized patients into Group 1 (KD and MIS-C) and Group 2 (other causes). We performed logistic regression analysis to identify factors associated with KD and MIS-C, using hospitalization days and levels of C-reactive protein (CRP), ferritin, and D-dimer. We calculated sensitivity, specificity, and likelihood ratio values and generated ROC (Receiver operating characteristic) curves. The threshold for statistical significance was set at P<0.05. Results: This study encompassed 243 patients with prolonged fever. The primary causes of admission included infection-related illnesses (60.91%, n=148), MIS-C (18.52%, n=45), and KD (10.70%, n=26). Significant differences were observed in lymphocyte count (P<0.001), CRP level (P<0.001), ferritin level (P<0.001), D-dimer level (P<0.001), hospitalization days (P<0.001), and echocardiographic findings (P<0.001) between the groups. Logistic regression analysis revealed noteworthy associations between the presence of KD and MIS-C and hospitalization days (P=0.001), elevated CRP levels (P=0.018), elevated ferritin levels (P=0.009), and elevated D-dimer levels (P=0.001). Ferritin exhibited an AUC (Area under curve) of 0.737 (P<0.001), and D-dimer demonstrated an AUC of 0.782 (P<0.001) in differentiating between the presence of KD and MIS-C. Conclusion: The prevalence of infectious and inflammatory conditions remains high in cases of prolonged fever, with a noticeable increase in the occurrence of KD and MIS-C since the onset of the COVID-19 pandemic. Notably, ferritin, CRP, and D-dimer levels are valuable indicators for identifying children at elevated risk of developing KD and MIS-C. While data were collected during the epidemic, additional data collection beyond this period would be necessary.