The expression of C-reactive protein, erythrocyte sedimentation rate, and procalcitonin in children with Kawasaki disease and their correlation with coronary artery ectasia

Abstract

Background

Coronary artery ectasia (CE) is the most severe complication in children with Kawasaki disease (KD) and increases the risk of long-term cardiovascular events This study aims to investigate the effects of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and procalcitonin (PCT) on KD children, as well as the discriminative ability of these biomarkers for identifying CE.

Methods

A total of 130 KD children were recruited as research subjects, consisting of 65 cases without CE (KD-nCE group) and 65 cases with CE (KD-CE group). The differences in baseline clinical information and complete blood count between the KD-nCE and KD-CE groups were analyzed using chi-square tests and t-tests. The correlations of CRP, ESR, and PCT with the coronary artery inner diameter were evaluated using Spearman and Pearson methods. The relationships between CRP, ESR, and PCT and the development of CE in KD children were determined using logistic regression and receiver operating characteristic (ROC) curves.

Results

The serum levels of WBC, PLT, CRP, ESR, and PCT were higher in the KD-CE group than in the KD-nCE group. Moreover, serum CRP, ESR, and PCT levels showed potential correlations with the coronary artery inner diameter in KD children. CRP, ESR, and PCT levels were identified as factors associated with the development of CE in KD children, and elevated levels of these three biomarkers were related to an increased likelihood of CE.

Conclusion

Serum levels of CRP, ESR, and PCT are correlated with the presence of CE in KD patients, and the combined assessment of these three biomarkers may provide discriminative value for identifying CE in KD.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12887-026-07016-w.

Background

Kawasaki disease (KD) is a self-limiting systemic vasculitis syndrome, predominantly occurring in children under the age of 5. The main clinical manifestations include fever, bilateral bulbar diffuse conjunctival injection, strawberry tongue, rash, cervical lymphadenopathy, and induration and swelling of the extremities [1, 2]. According to the latest revision of diagnostic guidelines [3], KD can be classified into complete KD and incomplete KD based on clinical symptoms. Additionally, it can be divided into KD with coronary artery lesions and KD without coronary artery lesions based on the presence or absence of coronary artery lesions. Coronary arteries are typically affected during weeks 2 to 4 of the disease course in KD patients [4], leading to coronary artery damage. These lesions can result in complications such as dilation, aneurysms, and thrombosis [5]. Coronary artery lesions in KD are caused by a complex cascade of immune responses, including inflammatory cell infiltration, extracellular matrix degradation, vascular basement membrane destruction, and cellular necrosis, which collectively contribute to the damage [6]. Coronary artery ectasia (CE) is one of the most severe complications in children with KD and markedly increases the risk of long-term cardiovascular events, thereby exerting a negative impact on patient prognosis [7]. Studies have shown that in children with KD who do not receive timely intervention, approximately 25% will develop CE or coronary artery aneurysms [8]. At present, coronary angiography is considered the “gold standard” for diagnosing coronary artery disease due to its sensitivity to changes in the vascular lumen. It allows for precise assessment of the severity of coronary artery stenosis and the formation of collateral circulation [9]. However, as an invasive examination, coronary angiography carries clear risks of complications and radiation exposure, limiting its use in the long-term follow-up of KD.

Currently, the exact cause of KD remains unknown but is primarily believed to be associated with immune inflammation, genetic susceptibility, and environmental factors [2]. C-reactive protein (CRP) is an acute-phase reactant that can rapidly increase in response to inflammatory stimuli. It may participate in vascular inflammation through various mechanisms, impacting vascular endothelial function [10]. Erythrocyte sedimentation rate (ESR) refers to the rate at which red blood cells in the blood settle in a given unit of time. It is a commonly used indirect marker to reflect inflammation and infection [11]. Procalcitonin (PCT) is an acute soluble protein that reflects the activity level of systemic inflammation. The concentration of PCT in the blood of a healthy body is relatively low, but it shows varying degrees of elevation during inflammatory responses. PCT can partially indicate the state of vascular inflammation [12]. The prognosis of KD is closely related to the severity of coronary artery lesions. Therefore, early diagnosis and timely treatment of KD are crucial in clinical research. Identifying effective serological markers to assist in distinguishing children with KD who are at risk of developing CE is of great importance for improving clinical outcomes. This study aims to analyze the serum levels of CRP, ESR, and PCT in children with KD and to examine their correlations with the occurrence of CE. The outcomes of this study may provide theoretical support and reference indicators to assist in the early clinical identification of CE.

Materials and methods

Research subjects

Referring to the KD diagnosis and treatment guidelines jointly developed by the American Academy of Pediatrics (AAP) and the American Heart Association (AHA), 130 children first diagnosed with KD at our hospital between January 2020 and December 2024 were enrolled as the study subjects. Patients should meet at least five of the following inclusion criteria: (1) Fever duration > 5 d, or fever duration < 5 d but responsive to intravenous immunoglobulin (IVIG); (2) Bilateral bulbar conjunctival injection (without exudate); (3) Erythema and cracking of lips, strawberry tongue, diffuse injection of the oral and pharyngeal mucosa; (4) Polymorphous rash; (5) Erythema of palms and soles, induration and swelling of the hands and feet in the acute phase, and membranous desquamation of at the junction of the nail bed and the surrounding skin on the fingers or toes in the convalescent phase; (6) Acute, non-suppurative cervical lymphadenopathy (usually unilateral, diameter > 1.5 cm) [7]. CE was diagnosed based on the coronary artery Z-score, as recommended by the American Heart Association guidelines for KD [8]. A Z-score > 2.5 relative to the body surface area-adjusted normal segment of the same artery was considered indicative of CE, confirmed by two independent pediatric cardiologists via echocardiography. ‘Diameter exceeding 1.5 times the adjacent segment’ [13] was noted for historical context but not employed for patient classification in this study to ensure methodological consistency. Exclusion criteria: prior IVIG treatment before admission; coexisting cardiac underlying diseases such as cardiomyopathy, chronic heart failure, or congenital heart disease; coexisting autoimmune diseases such as systemic lupus erythematosus or Henoch-Schönlein purpura; inability to complete relevant examinations.

Based on the presence or absence of CE, the patients were categorized into the KD-nCE group without CE (n = 65) and the KD-CE group with CE (n = 65). The flowchart illustrating the inclusion and exclusion of study participants is presented in Fig. S1. This study was approved by the Ethics Committee of Women and Children’s Hospital of Ningbo University (NBFE-2025-KY-137) and was conducted in accordance with the 1964 Declaration of Helsinki. Written informed consent was obtained from the parents or legal guardians of all participants.

Subject data collection

Baseline clinical data, including sex, age, fever duration, and time to diagnosis, were collected at enrollment. Laboratory parameters were obtained within 24 h after admission and before treatment initiation, including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), fibrinogen (FIB), activated partial thromboplastin time (APTT), white blood cell count (WBC), platelet count (PLT), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and procalcitonin (PCT) levels. Echocardiographic assessments were performed within 48 h after admission and prior to treatment by two experienced pediatric cardiologists. The sonographers were blinded to the patients’ laboratory results to minimize subjective bias.

Statistical analysis

Data were analyzed using SPSS 21 software (SPSS, Chicago, Illinois, USA), and plots were drawn using GraphPad Prism (Version 8; La Jolla, CA, USA). The normality of the data was examined using the Shapiro-Wilk test. For continuous variables with a normal distribution, data were presented as mean ± standard deviation (mean ± SD). For variables with a non-normal distribution, data were expressed as median and interquartile range (IQR). The normally distributed continuous variables were compared using the Student’s t-test, while the non-normally distributed variables were compared using the Mann-Whitney U test. Correlations between variables were assessed using bivariate analysis. Logistic regression analysis was used to identify factors associated with the development of CE in children with KD. The logistic regression analysis was verified by the Hosmer-Lemeshow test and the bootstrap method. The cutoff values obtained from the receiver operating characteristic (ROC) curves were used to evaluate the discriminative ability of CRP, ESR, and PCT for distinguishing CE in KD. P < 0.05 was considered statistically significant.

Results

Clinical baseline information of the subjects

A total of 130 children diagnosed with KD in the hospital were retrospectively selected as the research subjects. Based on whether they experienced CE, the patients were divided into the KD-nCE group (n = 65, without CE) and the KD-CE group (n = 65, with CE). The duration of fever was longer in the KD-CE group compared to the KD-nCE group, and this difference was statistically significant (P < 0.05, Table 1). No statistically significant differences were observed between the two groups in terms of sex, age, season of onset, or time from onset to diagnosis (P > 0.05, Table 1).

Table 1.

Comparison of general information between the two groups

	KD-nCE group (n = 65)	KD-CE group (n = 65)	χ2/t	P
Sex (n, %)
Male	38 (58.46%)	44 (67.69%)	1.189	0.276
Female	27 (41.54%)	21 (32.31%)
Age (months)	22 (14,51)	28(17,53.5)	-	0.201
Season of onset (n, %)
Non-winter	33 (50.77%)	31 (47.69%)	0.123	0.726
Winter	32 (49.23%)	34 (52.31%)
Fever duration (d)	5(5,7)	7(6,8)	-	0.002
Time from onset to diagnosis (d)	5(5,6)	5(5,6)	-	0.181

Comparison of test indicators between the two groups

The laboratory test results and clinical data, such as cardiac ultrasound, were collected for the two groups. The serum levels of WBC, PLT, CRP, ESR, and PCT in the KD-CE group were higher than those in the KD-nCE group, with statistically significant differences (P < 0.05). There were no statistically significant differences in serum levels of ALT, AST, FIB, and APTT between the two groups (P > 0.05, Table 2).

Table 2.

Comparison of test indicators between the two groups

	KD-nCE group (n = 65)	KD-CE group (n = 65)	t	P
ALT (IU/L)	51.55 ± 15.10	53.04 ± 18.22	0.507	0.613
AST (IU/L)	47.97 ± 12.97	43.34 ± 15.45	1.852	0.066
FIB (mg/dL)	546.13 ± 78.42	538.55 ± 94.79	0.497	0.620
APTT (s)	34.28 ± 3.42	34.71 ± 3.14	0.740	0.461
WBC (×109/L)	14.99(13.22,15.69)	16.16(14.33,19.25)	-	< 0.001
PLT (×109/L)	336.77 ± 97.09	390.60 ± 142.17	2.521	0.013
CRP (mg/L)	46.65(37.38,64.95)	65.82(54.02,85.00)	-	< 0.001
ESR (mm/h)	46.63 ± 16.79	67.01 ± 22.94	5.780	< 0.001
PCT (µg/L)	0.53(0.38,0.75)	0.73(0.54,1.07)	-	< 0.001
Inner diameter of left coronary artery (mm)	2.16 ± 0.28	2.71 ± 0.34	10.195	< 0.001
Inner diameter of right coronary artery (mm)	1.90 ± 0.27	2.18 ± 0.28	5.773	< 0.001

Correlations between serum CRP, ESR, and PCT levels and the coronary artery inner diameter

Pearson and Spearman correlation analyses showed that the pre-treatment serum levels of CRP, ESR, and PCT were potentially correlated with the inner diameter of the coronary arteries in children with KD (all P < 0.05, Fig. 1A-B).

Fig. 1.

Correlations between pre-treatment serum CRP, ESR, and PCT levels and the inner diameter of left and right coronary arteries. A: Correlations between pre-treatment serum CRP, ESR, and PCT levels and the inner diameter of left coronary arteries. B: Correlations between pre-treatment serum CRP, ESR, and PCT levels and the inner diameter of right coronary arteries.

Multifactorial analysis of factors associated with the occurrence of CE in children with KD

CE was used as the dependent variable (0 = no CE, 1 = with CE). Fever duration and serum levels of WBC, PLT, CRP, ESR, and PCT were used as variables. Multifactorial analysis revealed that serum CRP, ESR, and PCT levels were factors associated with the occurrence of CE in children with KD (all P < 0.05, Table 3). Collinearity diagnostics showed no significant multicollinearity among the variables (all VIF < 5, Table S1). The Hosmer-Lemeshow test indicated good model fit (P > 0.5, Table S2). Internal validation using bootstrap resampling (Table S3) further confirmed that serum CRP, ESR, and PCT levels had discriminative ability for identifying CE in KD.

Table 3.

Multifactorial analysis of factors associated with the occurrence of CE in children with KD

	β	SE	Wald	P	Exp(β)	95% CI
Fever duration	0.437	0.189	5.331	0.021	1.548	1.068–2.243
WBC	0.193	0.096	4.078	0.043	1.213	1.006–1.463
PLT	0.001	0.002	0.326	0.568	1.001	0.997–1.006
CRP	0.030	0.012	5.659	0.017	1.030	1.005–1.056
ESR	0.044	0.014	9.738	0.002	1.045	1.016–1.074
PCT	3.372	1.020	10.927	0.001	29.126	3.945-215.032

Discriminative ability of CRP, ESR, and PCT for identifying CE in KD children

To further explore the auxiliary diagnostic value of serum CRP, ESR, and PCT levels for identifying CE in children with KD, ROC curves were generated for each biomarker to distinguish the subjects between the two groups. The area under the ROC curve (AUC) for CRP in distinguishing KD children with CE was 0.7128, with a cutoff value of 59.76 (specificity 69.23%, sensitivity 64.62%) (Fig. 2A). The AUC for ESR was 0.7660, with a cutoff value of 44.97 (specificity 60.00%, sensitivity 84.62%) (Fig. 2B). The AUC for PCT was 0.7457, with a cutoff value of 0.8150 (specificity 86.15%, sensitivity 49.23%) (Fig. 2C). Subsequently, ROC curve analysis was performed to evaluate the combined discriminative ability of CRP, ESR, and PCT (Fig. 2D). The combined model yielded an AUC of 0.8691, with a specificity of 86.15% and a sensitivity of 72.31%. These findings indicate that the combination of CRP, ESR, and PCT may provide superior discriminative performance for identifying CE in children with KD (Table 4; Fig. 2).

Fig. 2.

Discriminative ability of CRP, ESR, and PCT for identifying CE in children with KD. A: Discriminative ability of CRP for identifying CE in children with KD. B: Discriminative ability of ESR for identifying CE in children with KD. C: Discriminative ability of PCT for identifying CE in children with KD. D: Discriminative ability of the combination of CRP, ESR and PCT for identifying CE in children with KD.

Table 4.

Discriminative ability of CRP, ESR, and PCT for identifying CE in children with KD

	AUC		95% CI	SE	P	Specificity (%)	Sensitivity (%)
CRP	0.7128	0.6246–0.8010		0.045	< 0.0001	69.23	64.62
ESR	0.7660		0.6851–0.8470	0.041	< 0.0001	60.00	84.62
PCT	0.7457		0.6635–0.8279	0.042	< 0.0001	86.15	49.23
Combination	0.8691		0.8085–0.9297	0.031	< 0.0001	86.15	72.31

Discussion

The pathological features of KD involve systemic inflammation of medium and small blood vessels (particularly the coronary artery wall), multiple organs, and tissues. Among these, coronary artery lesions represent the most severe complication of KD and may persist for months or even years [14]. In the early stage of the disease, CE and coronary arteritis are the predominant manifestations [8]. Therefore, early identification and timely intervention for CE in KD have become major research priorities in this field. Identifying relevant risk factors is crucial for understanding disease progression and for developing targeted therapeutic strategies.

This study included 65 KD patients without CE and 65 KD patients with CE to examine the expression differences of CRP, ESR, and PCT between the two groups and evaluate their diagnostic value for CE in KD patients. The exact pathogenesis of coronary artery lesions in KD children remains incompletely understood. However, during the stages of vascular pathological changes, the involvement of inflammatory-related factors is indispensable [15]. Systemic inflammatory responses can damage the elastic layer and smooth muscle of the vascular wall, resulting in various vascular complications, such as coronary artery lesions, coronary artery aneurysms, and myocarditis [16]. CRP and PCT are widely recognized clinical inflammation markers, and most studies have demonstrated that CRP and PCT levels are positively correlated with the severity of KD in patients [17]. The first study on PCT as a predictive marker for KD reveals that there is an association between PCT levels and the development of coronary artery aneurysms in KD patients. However, the study has significant limitations due to its small sample size (including only 25 Japanese patients) [18]. In addition, a study with a larger sample size has detected the PCT levels of 160 Japanese KD patients. The analysis validates that PCT is a better indicator than CRP and WBC for assisting in the assessment of disease severity [19]. During the acute phase of KD, ESR remains persistently elevated. However, after IVIG administration, ESR may no longer serve as a reliable marker of disease activity and cannot effectively reflect the therapeutic response to IVIG [20]. Indeed, although numerous studies have examined the auxiliary diagnostic value of CRP, ESR, or PCT individually in KD, research simultaneously evaluating all three biomarkers in relation to the development of CE remains limited. Given the complex interactions among inflammatory mediators, single inflammatory markers are likely to be impacted by multiple factors [21]. Thus, their individual diagnostic performance in assessing disease severity in KD may be suboptimal. Although serum CRP, ESR, and PCT levels were positively correlated with the coronary artery inner diameter (P < 0.05), the correlation coefficients were relatively low (r = 0.2–0.3). These weak associations suggest that these inflammatory markers have only a modest relationship with the degree of coronary dilation. In contrast, multivariate regression and ROC analyses demonstrated that the combination of CRP, ESR, and PCT improved the specificity (86.15%) and sensitivity (72.31%) for identifying CE, meeting the requirements for clinical applicability.

This study has several limitations. First, it was conducted at a single center, with a limited number of enrolled cases and observed variables, and it lacked external validation, which may increase the risk of overfitting during data analysis. Although variable selection and internal validation were applied to mitigate this issue, larger multicenter cohorts are needed to further verify the robustness of the model. Second, although laboratory data were collected within 24 h of admission and prior to IVIG administration, the issue of disease timing remains a limitation. Inflammatory markers such as CRP, ESR, and PCT fluctuate dynamically throughout the course of KD, and the observed elevations in these biomarkers may have been affected by differences in disease stage. Future studies should aim to match patients more strictly according to illness day. Moreover, several potentially important confounding factors were not fully adjusted for, including complete/incomplete KD classification, timing of IVIG administration, IVIG resistance, adjunctive therapies, the interval from fever onset to echocardiography, and concurrent infections. These factors may impact inflammatory status or coronary outcomes and thereby confound the associations between CRP, ESR, PCT, and CE. For example, IVIG resistance or delayed treatment may exacerbate inflammation and elevate biomarker levels, whereas the lack of Z-score adjustment for age and body size may lead to misclassification of CE. However, because this was a retrospective study, the variables mentioned above were not recorded and therefore could not be retrieved. In future studies of a similar design, we will ensure that these factors are incorporated so as to better control for potential confounding and provide stronger support for the study conclusions. In addition, this study focused solely on the association between CE and inflammatory markers and did not track the progression from CE to coronary artery aneurysm. As a result, long-term outcomes could not be assessed. Longitudinal studies are warranted to further explore this progression.

Abbreviations

CE

Coronary artery ectasia

KD

Kawasaki disease

CRP

C-reactive protein

ESR

Erythrocyte sedimentation rate

PCT

Procalcitonin

ROC

Receiver operating characteristic

AAP

American Academy of Pediatrics

AHA

American Heart Association

IVIG

Intravenous immunoglobulin

ALT

Alanine aminotransferase

AST

Aspartate aminotransferase

FIB

Fibrinogen

APTT

Activated partial thromboplastin time

WBC

White blood cell count

PLT

Platelet count

IQR

Interquartile range

Authors' contributions

Cang Lyu: Writing – original draft, Methodology, Formal analysis, Data curation. Chunyan Fang, Zhengxia Liu and Jin Wang: Data curation, Formal analysis, Writing – review & editing. Zhongyan Xu and Yun Zhou: Data curation, Investigation, Writing – review & editing. Wei Jiang: Writing – review & editing.

Funding

This research was funded by Ningbo Natural Science Foundation (No. 2024J312), Medical and Health Science and Technology Project of Zhejiang Province (No. 2025KY272), Zhejiang Clinovation Pride (No. CXTD202502005), and NINGBO Leading Medical & Health Discipline (No. 2026-A34).

Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

This study was approved by the Ethics Committee of Women and Children’s Hospital of Ningbo University’s ethics committee (NBFE-2025-KY-137). This research complies with the 1964 Declaration of Helsinki. This study obtained the informed consent of the parents or legal guardians of the participants.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.