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BACKGROUND The goal of this study is to evaluate the changes in the epidemiologic and clinical features of Kawasaki disease (KD) in a period of 20 years. METHODS We compared the epidemiologic features of 3 KD patient groups: those admitted from 1987 to 1990 (122 cases), from 1997 to 2000 (137 cases) and from 2007 to 2010 (102 cases). For clinical features, we reviewed the medical records of patients admitted from 1996 to 2000 (141 cases) and from 2006 to 2010 (121 cases). RESULTS There were a total of 772 KD patients during the study period (mean age: 27.2 months; male-to-female ratio: 1.6:1). There were some variations in the mean ages (23.8, 27.8 and 30 months), in the male-to-female ratios (1.9:1, 1.3:1 and 1.8:1) and in the age distributions, including the patients of ages 5 years, but the differences were not statistically significant across the groups. The seasonal distributions were relatively consistent with some variations. In clinical features, the preadmission and total fever durations were shorter (P < 0.001, respectively), and the proportions of incomplete KD tended to increase, and the rates of coronary artery aneurysm tended to decrease in recently admitted patients. CONCLUSIONS There were no significant changes in the demographic and seasonal features of KD, although the evaluation of the clinical features showed shorter fever duration suggestive of improved identification and treatment of KD over time.

A missense mutation in mouse Nek8 , which encodes a ciliary kinase, produces the juvenile cystic kidneys ( jck ) model of polycystic kidney disease, but the functions of Nek8 are incompletely understood. Here, we generated a Nek8- null allele and found that homozygous mutant mice die at birth and exhibit randomization of left-right asymmetry, cardiac anomalies, and glomerular kidney cysts. The requirement for Nek8 in left-right patterning is conserved, as knockdown of the zebrafish ortholog caused randomized heart looping. Ciliogenesis was intact in Nek8- deficient embryos and cells, but we observed misexpression of left-sided marker genes early in development, suggesting that nodal ciliary signaling was perturbed. We also generated jck/Nek8 compound heterozygotes; these mutants developed less severe cystic disease than jck homozygotes and provided genetic evidence that the jck allele may encode a gain-of-function protein. Notably, NEK8 and polycystin-2 (PC2) proteins interact, and we found that Nek8 −/− and Pkd2 −/− embryonic phenotypes are strikingly similar. Nek8 -deficient embryos and cells did express PC2 normally, which localized properly to the cilia. However, similar to cells lacking PC2, NEK8-depleted inner medullary collecting duct cells exhibited a defective response to fluid shear, suggesting that NEK8 may play a role in mediating PC2-dependent signaling.

Background: Some patients with intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) do not respond to intravenous methylprednisolone (IVMP). Infliximab (IFX; anti-TNF-α antibody) is an alternative medication for intractable KD. Its effectiveness in preventing coronary aneurysms from progressing is being reported. We herein report a case of intractable KD that slowly progressed to giant aneurysm despite a second IFX infusion. Methods: A 2-year-old boy visited our hospital with a 2-day history of fever. On day 3 after fever onset, a swollen cervical lymph node, redness of the BCG (bacilli Calmette Guérin) inoculation site, and indurated erythema of the palms with soles were observed. On day 5, conjunctival injection, strawberry tongue, red lips and truncal rash were present. The patient was diagnosed with KD and treated with IVIG and acetylsalicylic acid (ASA). Results: The fever persisted for 24 h after IVIG treatment. A second dose of IVIG was infused. However, the fever continued. Then IVMP was infused. On day 9, the fever resolved. On day 10, two-dimensional echocardiography (2DE) showed mild dilations (Φ 3.0 mm) of both coronary arteries (CAs). On day 18, the fever recurred. Follow-up 2DE showed dilated CAs (left main coronary artery [LM], Φ 4.0 mm; right coronary artery [RCA], Φ 4.0 mm). Therefore, IFX was intravenously infused. On day 19, the fever had resolved and the patient went home. On day 22, the fever recurred. Thus, a second infusion of IFX was done. On day 24, the fever resolved. Follow-up 2DE showed that the diameters of the CAs were 4.0 mm (LM), 7.0 mm (left anterior descending coronary artery [LAD]), 3.0 mm (RCA). On day 28, a mild fever was still present. On day 47, follow-up 2DE indicated that the diameters of the CAs were 3.0 mm (LM), 8.0 mm (LAD), 2.5 mm (RCA). On day 159, follow-up 2DE showed slightly increased regression of CAs. The patient has been undergoing regular 2DE and taking ASA since he left the hospital. Conclusions: This was a very rare case of KD that was resistant to standard treatment comprising high-dose steroids and TNF-α blockade. We have reported this case to inform clinicians who may encounter such patients with KD in the future. A high index of suspicion and keen observations are strongly recommended for cases of intractable KD.

Objectives: A high-dose (2g/kg) intravenous immunoglobulin (IVIG) has been generally incorporated into the acute treatment protocols for Kawasaki disease (KD), with ongoing debates on this issue. The aim of this study was to assess the effectiveness of medium-dose (1g/kg) IVIG as an initial treatment of KD in Korean children. Methods: A retrospective study was done in a total of 255 children with KD, in whom 91 patients (group 1, mean age; 2.8 ± 2.5 years) had 2g/kg of IVIG and 164 patients (group 2, mean age; 2.7 ± 1.7 years) had 1g/kg of IVIG as an initial treatment of KD, along with 30-50 mg/kg of aspirin. Echocardiography (Echo) was done during admission, around 2 weeks, 2 months, and 1 year after the onset of fever according to our protocol. Patients who completed one-year Echo study were included in this study. Patients’ demographic, laboratory, and Echo findings were recorded, and compared between groups. Coronary artery lesions (CAL) were defined as a coronary artery diameter > 2 SD of normal mean for age or coronary artery stenosis. The primary end point was the incidence of CAL at 1 year after treatment. The secondary end points were the incidence of CAL at 2 weeks and 2 months study, and clinical outcomes. Comparisons between groups were done using an unpaired t-test or Fisher’s exact test. Results: There was no significant difference in age, gender, and laboratory findings before treatment between the two groups. Group 1 had higher incidence of CAL at 2 weeks (32/91, 35.2 % vs. 33/164, 20.2 %, p = 0.011), but similar incidence of CAL at 2 months (18/91, 19.8% vs. 24/164, 14.6%, p > 0.05) and 1 year (6/91, 6.6% vs. 10/164, 6.1%, p > 0.05) compared with group 2. Group 1 had a higher proportion of patients needed additional dose of IVIG (23/91, 25.3% vs. 15/164, 9.1%, p = 0.001), but received significantly lower total dose of IVIG (1.3 ± 0.7 g/kg vs. 2.1 ± 0.5 g/kg, p < 0.001) compared with group 2. There was no difference in duration of fever after IVIG and duration of hospital stay between the two groups. Conclusion: This study demonstrated that medium-dose IVIG is as effective as high-dose IVIG for the treatment of KD in terms of CAL prevention, defervescence, and duration of hospital stay. Further prospective and randomized study is needed to verify this.

Background: Very young infants with Kawasaki disease (KD) often present with atypical features that render diagnosis difficult and the incidence of coronary complications high. Picking up clues at early phase of KD can be critical. Herein we present 3 cases of KD in very young infants who showed mitral regurgitation (MR) around the 7th day from the onset of fever. They received IVIG around 7th fever day. However, the advice for short-term follow up echocardiography (ECHO) was neglected as clinical course thereafter were so unusual. Giant coronary aneurysms developed in all the patients later. Case 1: A 31-day-old infant got admission care for sepsis. ECHO at the 7th day from the onset of fever showed trivial MR and the patient received IVIG. Follow up ECHO was recommended, but was not conducted as clinical course was ambiguous for KD thereafter. Being treated with steroids due to skin rash and eosinophilia that masked patient’s fever, the infant reappeared to hospital with cardiogenic shock 10 days later. ECHO revealed giant aneurysms in the right coronary artery (RCA) and CT angiography for pulsating axillary masses revealed axillary aneurysms. Case 2; A 67-day-old infant was admitted with fever and persistent thrombodytopenia. ECHO done at the 5th day from the onset of fever due to red lips showed non-specific findings. Follow up ECHO at the 7th fever day showed newly developed MR. IVIG and steroids was added on for persistent fever, but severe leukocytosis ensued and clinical course was also ambiguous for KD. Defervescence was achieved with infliximab. The infant showed coronary aneurysms. Case 3; A 80-day-old infant was admitted with fever and seizure, and treated for sepsis. On the 6th day from the onset of fever, MR was shown on ECHO and the patient received IVIG and steroids. However, fever and severe anemia, left shift of leukocytes, and severe thrombocytopenia persisted for two weeks. Giant coronary aneurysms, as large as the ascending aorta, developed in the RCA. Pulsatile masses identified in the axilla were found to be large aneurysms on CT angiography. Conclusion: A newly developed MR, even trivial, around the 7th day from the onset of fever may be a clue to the diagnosis of KD and short term follow up ECHO is recommended for ongoing febrile infants younger than 3 months.