In this retrospective analysis of the 9th Korean nationwide survey of KD, the development of CAL was also found in patients with low serum CRP levels. In the low CRP group, CAL was observed in 18.3% and 12.5% of patients during the acute phase and 8.5% and 6.8% of patients after the convalescent period based on the z-score and Japanese criteria, respectively. CAL occurrence was higher in the low CRP group than in the high CRP group. Our study design did not allow us to identify or define the cause of this observation. However, patients in the low CRP group were younger at KD diagnosis and more often presented with incomplete KD, which may be associated with a higher CAL occurrence than in patients in the high CRP group.1, 9, 10
In general, the risk assessment of coronary artery complications is evaluated based on IVIG responsiveness, and high serum CRP levels are regarded as a related factor for the non-responsiveness to IVIG.11, 12 The CRP value used to predict this non-responsiveness to IVIG is the initial CRP level, which reflects the inflammatory state prior to IVIG treatment. However, the initial serum CRP level alone may not be sufficient to predict complications. Nandi et al. showed a difference in the CRP and interleukin-6 (IL-6; a cytokine that stimulates inflammatory markers, including CRP) levels between IVIG responders and non-responders. They found that CRP and IL-6 levels were higher after IVIG treatment in IVIG non-responders than in responders; however, these levels were not significantly different before IVIG treatment.5 High CRP levels after initial IVIG were also reported to be a risk factor for non-responsiveness to additional IVIG treatment in refractory KD patients.13, 14 Because the serum CRP levels after IVIG treatment were not investigated in this study, it is difficult to draw definitive conclusions, but we believe that the serum CRP level before IVIG treatment is insufficient to predict coronary artery complications.
In our study, the fever duration before treatment was not different between the low and high CRP groups, but there was a difference in responsiveness to IVIG treatment. In patients with low serum CRP levels, the rate of non-responsiveness to the first IVIG dose was 11.7%, which was considerably lower than the overall nonresponse rate (18.3%) to the first IVIG dose among all patients. In patients with low serum CRP levels, the response rate to the first IVIG dose was good, but coronary artery complications still occurred in some of these patients, which suggest that patients with low CRP levels may not be a homogeneous group. Some patients responded well to treatment without coronary complications, as would be expected based on their low CRP serum levels in others, coronary complications were found although they had appropriate treatment. One may hypothesize that a rise in CRP levels occurred after the initial test, but further research is required to test such a hypothesis.
In both groups, the presence of some principle symptoms was associated with a low risk of CAL. Notably, in the low CRP group, the presence of BCG site redness showed a low risk of CAL. Similar trends were identified in the high CRP group, with the presence of principle symptoms associated with a low risk of CAL. These results are in line with the findings of a previous study, which showed that coronary artery complications may be high due to the delayed diagnosis and treatment of patients with incomplete KD who have insufficient clinical symptoms to match the diagnostic criteria.1
In this study, the characteristics of patients were similar to those of patients in the nationwide survey and other reported data.15–17 However, our results should be interpreted within the limitations of this study. Because this analysis was performed retrospectively, patients lacking essential data required to interpret the results of this study were excluded (n = 6256); thus, 9131 patients who met the inclusion criteria were analyzed. Furthermore, serum CRP levels were collected just prior to initial IVIG treatment, but the exact day of sampling from fever onset was not investigated.