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Background Coronary arterial aneurysms (CAAs) associated with Kawasaki disease (KD) significantly affect prognosis. However, the clinical course of CAAs and factors associated with CAA regression have not been well analyzed. Methods and Results The cohort of the Z-Score 2nd Project Stage study, a multicenter, retrospective, cohort study involving 44 institutions in Japan including 1006 patients with KD, was examined. CAAs were classified by the z score of their internal diameter in the acute phase: small ( z <5), medium (5≤ z <10), and large ( z ≥10). The lower limit of small CAA was based on the Japanese Ministry of Health, Labour and Welfare criteria. In the right coronary artery, the CAA regression rates 10 years after diagnosis were 95.5% for small, 83.2% for medium, and 36.3% for large. In the proximal left anterior descending artery, the regression rates 10 years after diagnosis were 95.3% for small, 80.1% for medium, and 28.8% for large. Cox regression analysis showed that diagnosis under the age of 1 year and onset of KD in 2010 to 2012 for the right coronary artery and the left anterior descending artery, and female for the right coronary artery were significantly associated with a high regression rate, whereas large CAAs for the right coronary artery and the left anterior descending artery were significantly associated with a low regression rate. Conclusions The current study, the largest Japanese study of its kind, found that small aneurysm, recent onset, and diagnosis under the age of 1 year predict regression, and that even giant aneurysms could regress. These data may contribute to long-term management of coronary aneurysms. Registration URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000010606.

Importance: Few studies with sufficient statistical power have shown the association of the z score of the coronary arterial internal diameter with coronary events (CE) in patients with Kawasaki disease (KD) with coronary artery aneurysms (CAA)., Objective: To clarify the association of the z score with time-dependent CE occurrence in patients with KD with CAA., Design, Setting, and Participants: This multicenter, collaborative retrospective cohort study of 44 participating institutions included 1006 patients with KD younger than 19 years who received a coronary angiography between 1992 and 2011., Main Outcomes and Measures: The time-dependent occurrence of CE, including thrombosis, stenosis, obstruction, acute ischemic events, and coronary interventions, was analyzed for small (z score, <5), medium (z score, ≥5 to <10; actual internal diameter, <8 mm), and large (z score, ≥10 or ≥8 mm) CAA by the Kaplan-Meier method. The Cox proportional hazard regression model was used to identify risk factors for CE after adjusting for age, sex, size, morphology, number of CAA, resistance to initial intravenous immunoglobulin (IVIG) therapy, and antithrombotic medications., Results: Of 1006 patients, 714 (71%) were male, 341 (34%) received a diagnosis before age 1 year, 501 (50%) received a diagnosis between age 1 and 5 years, and 157 (16%) received a diagnosis at age 5 years or older. The 10-year event-free survival rate for CE was 100%, 94%, and 52% in men (P < .001) and 100%, 100%, and 75% in women (P < .001) for small, medium, and large CAA, respectively. The CE-free rate was 100%, 96%, and 79% in patients who were not resistant to IVIG therapy (P < .001) and 100%, 96%, and 51% in patients who were resistant to IVIG therapy (P < .001), respectively. Cox regression analysis revealed that large CAA (hazard ratio, 8.9; 95% CI, 5.1-15.4), male sex (hazard ratio, 2.8; 95% CI, 1.7-4.8), and resistance to IVIG therapy (hazard ratio, 2.2; 95% CI, 1.4-3.6) were significantly associated with CE., Conclusions and Relevance: Classification using the internal diameter z score is useful for assessing the severity of CAA in relation to the time-dependent occurrence of CE and associated factors in patients with KD. Careful management of CE is necessary for all patients with KD with CAA, especially men and IVIG-resistant patients with a large CAA.

Kawasaki disease (KD) is the most common cause of multisystem vasculitis in childhood. Although cervical lymphadenitis is one of the major symptoms in KD, lymph node biopsy is rarely performed, because KD is usually diagnosed by clinical symptoms. A cervical lymph node biopsy was taken from a girl aged 1 year and 8 months who had suspected lymphoma, but she was diagnosed with KD after the biopsy. The cervical lymph node specimen was analyzed with multivirus real-time PCR that can detect >160 viruses, and unbiased direct sequencing with a next-generation DNA sequencer to detect potential pathogens in the lymph node. Histologically, focal necrosis with inflammatory cell infiltration, including neutrophils and macrophages, was observed in the marginal zone of the cervical lymph node, which was compatible with the acute phase of KD. Multivirus real-time PCR detected a low copy number of torque teno virus in the sample. Comprehensive direct sequencing of the cervical lymph node biopsy sample sequenced more than 8 million and 3 million reads from DNA and RNA samples, respectively. Bacterial genomes were detected in 0.03% and 1.79% of all reads in DNA and RNA samples, respectively. Although many reads corresponded to genomes of bacterial environmental microorganisms, Streptococcus spp. genome was detected in both DNA (77 reads) and RNA (2,925 reads) samples. Further studies are required to reveal any association of microbial or viral infection with the pathogenesis of KD.

To identify the origin of urinary leukocytes in Kawasaki disease (KD) patients with pyuria, we prospectively studied clinical and laboratory findings of 23 KD patients. Patients were divided into three groups: patients without pyuria, patients with pyuria in both voided urine and bladder urine obtained by transurethral catheterization (bladder pyuria) and patients with pyuria only in voided urine (urethral pyuria). Pyuria in voided urine was found in ten of 23 KD patients (43.5%), with subsequent urine cultures proving sterile. Five out of ten patients with pyuria in voided urine also exhibited pyuria in bladder urine, whilst the remaining patients did not have pyuria in bladder urine. Urinary protein levels were higher in patients with bladder pyuria and in patients with urethral pyuria than in patients without pyuria. Urinary beta2-microglobulin concentrations and serum blood urea nitrogen (BUN) and creatinine levels were higher in patients with bladder pyuria than in patients with urethral pyuria or in patients without pyuria, although the serum BUN and creatinine levels of patients with bladder pyuria were within the normal ranges. These results suggest that some patients with KD develop sterile pyuria that originates from the urethra and/or the kidney as a result of mild and subclinical renal injury.

Although hyponatremia frequently occurs in Kawasaki disease (KD), the clinical characteristics of KD patients with hyponatremia and the pathogenesis of hyponatremia in KD remain unknown. The aims of this study were to define the clinical characteristics of KD patients with hyponatremia (serum sodium <135 mEq/l) and to determine the factors associated with its development. One hundred and fourteen patients with KD were included in this study. Fifty-one patients (44.7%) had hyponatremia. Coronary artery lesions and dehydration were significantly more common in patients with hyponatremia. The duration of fever was significantly longer in patients with hyponatremia. Pyuria and hematuria were present significantly more often in patients with hyponatremia. The serum concentrations of potassium, chloride and total cholesterol were significantly lower in patients with hyponatremia. Serum C-reactive protein and alanine aminotransferase were significantly higher in patients with hyponatremia. Some patients with pyuria and hyponatremia exhibited increased excretion of urinary tubular epithelial cells and urinary casts. There was no difference in the incidence of diarrhea between patients with hyponatremia and patients without hyponatremia. These results indicate that hyponatremia in KD occurs in patients exhibiting severe inflammation. Further studies will be necessary to confirm the pathogenic mechanisms of hyponatremia in patients with KD.