Serum ferritin as a crucial biomarker in the diagnosis and prognosis of intravenous immunoglobulin resistance and coronary artery lesions in Kawasaki disease: A systematic review and meta-analysis

Background: Early identification and treatment are paramount for intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs) in patients with Kawasaki disease (KD). Unfortunately, there is no single crucial biomarker to identify these patients in a timely manner, which makes KD the most common cause of acquired heart disease in children in developed countries. Recently, many studies have focused on the association between serum ferritin (SF), IVIG resistance, and CALs in KD. We thus performed a systematic review and meta-analysis to ascertain the diagnostic and prognostic values of SF in predicting IVIG resistance and CALs in KD in the acute phase. Methods: The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the receiver operating characteristic curve (AUC) were extracted from the data to evaluate the SF levels in KD. The hazard ratios (HRs) of related risk factors and their corresponding 95% confidence intervals (CIs) were applied to compute the pooled assessments of the outcomes. Results: A total of 11 eligible articles were included in this meta-analysis, including twenty studies for diagnosis and five studies for prognosis. In terms of diagnostic values, SF could identify KD patients in the overall studies with a relatively high pooled sensitivity, specificity, PLR, NLR, DOR, and AUC of 0.89), respectively. In studies comparing KD patients and controls, there were a relatively high pooled sensitivity, specificity, PLR, NLR, DOR, and AUC of 0.79 (95% CI: 0.72-0.84), 0.84 (95% CI: 0.79-0.91), 4.61 (95% CI: 3.27-6.51), 0.26 (95% CI: 0.20-0.34), 20.82 (95% CI: 11.83-36.64), and 0.89 (95% CI:0.86-0.91), respectively. For the prognostic values, we found poor survival outcomes based on KD patients (HR = 1.31, 95% CI: 1.07-1.59,P= 0.008). Conclusion: Our meta-analysis suggests that SF may be used as a workable and critical biomarker for the diagnosis and prognosis of IVIG resistance and CALs in patients with KD. We also propose that maintaining the dynamic balance between iron, SF, and ferroptosis will be an important therapeutic strategy to reduce the morbidity of CALs.

Automated summary

This meta-analysis investigated the diagnostic and prognostic values of serum ferritin (SF) in Kawasaki disease (KD). The results suggest that SF may serve as a critical biomarker for predicting IVIG resistance and coronary artery lesions (CALs) in patients with KD. Maintaining the dynamic balance of iron, SF, and ferroptosis could be an important therapeutic strategy to reduce the morbidity of CALs.