Kawasaki Disease: Laboratory Findings and an Immunopathogenesis on the Premise of a ""Protein Homeostasis System

Lee, Kyung-Yil; Rhim, Jung-Woo; Kang, Jin-Han

KD is a self-limiting disease. The total duration of fever in the era of non-IVIGs is 1-2 weeks (mean 10-11 days), regardless of treatment with aspirin or corticosteroids. 1, 53, 54 Therefore, a patient who is expected to have a total fever duration of 11 days reaches a peak in inflammatory processes at the sixth day after fever onset, if the periods of ascent to and regression from the peak are similar (Fig. 1) . We previously evaluated the inflammatory indices in KD patients according to the fever duration at presentation. Indeed, the levels of white blood cells (WBC) and neutrophil counts and CRP levels were highest, while the albumin and HDL-cholesterol levels were lowest, at the sixth day, and these indices showed a bell-shaped or U-shaped distribution trend based on these values at the sixth day (the peak) ( Fig. 2 ). 55 These findings suggest that the inflammatory processes of KD progress to a peak, then regress to a convalescent stage during the febrile period. It also suggests that in cases of CALs, the immune cells involved in tissue destruction (endothelial damage) have a predominant role in the early stages and the immune cells involved in tissue repair have a predominant role in the late stages of KD, and the results are reflected by laboratory findings. The transaminases (AST and ALT) appear to be higher in the early days, and markedly decrease after the peak stage of KD. Total cholesterol level may be the lowest in the early days and tends to increase along with the natural course of inflammation. Platelet count is well known to increase in convalescent stages of KD. However, platelet count may begin to increase at the peak stage of KD, suggesting involvement in tissue repair (Fig. 2) . These findings may be useful for evaluation of the severity of patients who have the highest CALs, and were treated with IVIG. 2, 57, 58 However, now IVIG is recommended for all KD patients. IVIG has a potent anti-inflammatory effect on KD although its mode of action is unknown. It has been reported that approximately 10-15% of KD patients are IVIG non-responders. 17, 18, 25, [59] [60] [61] [62] [63] Early detection of IVIG non-responsiveness through laboratory values is a reasonable and simple method for the evaluation of severity of KD and for the selection of severely affected patients who need early intensive treatment. For this purpose, there have been a number of previous reports of putative predictive variables of IVIG non-responders. Laboratory markers including CRP, neutrophil differential including bands, albumin, sodium, hemoglobin, platelets, lactic dehydrogenase (LDH), total bilirubin, γ-GTP, ALT, and AST have been reported to differ significantly between IVIG non-responders and responders before IVIG infusion. 17, 18, 25, [59] [60] [61] [62] [63] These different laboratory predictors with the score systems for IVIG non-responsiveness, 17, 18 and the earlier Harada score system for risk of CALs may have a limitation resulting from confounding factors; difference of sample size, 64 the intensity of inflammation in individuals, the age of patients, 32 the stage of inflammation response at presentation as shown in Fig. 1 , 55 and possibly ethnicity. 25, 65 Some studies suggest that earlier IVIG treatment, particularly before day 5 of illness is associated with an increased risk of nonresponse to IVIG. 17, 18, 25, 63 It is plausible that IVIG non-responders might have more severe inflammation and more florid clinical symptoms and