The accurate diagnosis of KD remains a challenge for clinicians because its clinical manifestations are often similar to or overlap with other febrile infectious diseases in children, and no specific laboratory test is currently available to confirm the diagnosis. A recent study reported the existence of over diagnosis KD(17). The challenge for clinicians is to prevent the occurrence of coronary artery aneurysms (CAAs) based on the accurate diagnosis and precise treatment of KD. Therefore, establishing a prediction model to identify KD from other febrile infectious diseases is crucial. In this report, we reviewed the clinical data of 216 patients with KD and 394 patients with other febrile infectious diseases and established a new prediction model with high accuracy.
Peripheral blood total WBC is one of the predictors in this model, and it increases in the acute phase of KD. WBC can be used as a non-specific inflammatory indicator in combination with clinical manifestations to predict KD (18). WBC may also be able to predict the severity of systemic inflammation and IVIG non-reactivity in KD patients (19). Other studies have shown that a WBC count greater than 16*10^9/L is positively correlated with heart damage (20). Therefore, although the specificity of WBC is not high for KD, it is widely used in clinical practice and has practical significance for the clinical diagnosis of KD (21).
In this model, NLR (the ratio of neutrophil count to lymphocyte count of peripheral blood) is an important predictor for identifying KD. The immune response to inflammation includes neutrophils moving to the site of inflammation, releasing inflammatory cytokines, and activating T cells, which play a key role in the development of vascular inflammation. Lymphocytes are produced by lymphoid organs and play an important role in the body's immune response; they can also be used as a marker of immune regulation. Therefore, NLR is a reflection between inflammatory response and immunity balance. Some studies have shown that the higher the NLR value, the heavier the inflammatory response (22, 23). Recent studies have indicated that a high level of NLR is an independent influencing factor of IVIG resistance in KD (24).
Onodera's PNI is an index reflecting nutritional status. PNI has been reported to be a strong indicator for predicting the prognosis of patients with malignant tumors and has been widely used in predicting the prognosis, postoperative complications, and quality of life of a variety of tumors (25, 26). PNI was found as a novel surrogate independent predictor for IVIG-resistant KD according to resent study(27). In KD patients, the ALB levels were significantly lower than those of the febrile control group and even lower in KD with CAL formation (28).
Recent studies have reported that reduced lymphocyte count can serve as an independent predictor for IVIG resistance in KD (29). Onodera's PNI score is calculated based on these two indicators of lymphocyte and albumin and can reflect nutritional status and immune function. In this study, Onodera's PNI was an important predictor for distinguishing KD from other febrile diseases.
The plasma level of C3 in the KD group was significantly higher than in febrile controls and is also one of the important indicators for distinguishing KD from controls. C3 is involved in the three complement pathways (classical, lectin, and alternative pathway) and plays an important role in the innate immune response. Yan et al. have found that compared with fever control group, the level of C3 was significantly higher in KD group, and it was higher in IVIG sensitive group compared with IVIG nonresponsive group(7). Dysregulation or over activation of the complement system is the pathogenesis of vascular inflammation and aortic aneurysm formation (30, 31). However, few studies have addressed the complement pathway of KD (32, 33). Katayama et al. reported that Ficolin 1 inhibitory antibody injection improved vasculitis of the KD mouse model, further suggesting that the lectin pathway may be involved in the pathogenesis of KD (34).
This study is a single-center retrospective study with a relatively small number of cases, and a randomized controlled study with a larger sample of multiple centers is needed to further verify the value of the prediction model.