Tomoyoshi Sonobe

Revision of diagnostic guidelines for Kawasaki disease (the 5th revised edition)

Abstract  Diagnostic guidelines for Kawasaki Disease was revised to meet the present situation in 2002. This issue intends to explain new guidelines and their backgrounds. Major alterations are interpretation of cases with 4 or fewer febrile days shortened by early intravenous immunoglobulin treatment, and the clinical importance of atypical (incomplete, or suspected) cases.

Prevalence of coronary artery abnormality in incomplete Kawasaki disease

Background: The aim of the present study was to determine the prevalence of coronary artery abnormality (CAA) and other clinical features in patients with incomplete Kawasaki disease (iKD) using the data from the 17th Japanese nationwide survey of KD.

Use of laboratory data to identify risk factors of giant coronary aneurysms due to Kawasaki disease

Abstract Background : Although some laboratory findings are known to be indicators of the risk of giant coronary aneurysm formation among Kawasaki disease patients, an appropriate cut‐off point to predict aneurysm formation is not clear.

Risk Stratification in the Decision to Include Prednisolone With Intravenous Immunoglobulin in Primary Therapy of Kawasaki Disease

Background: We reported previously that intravenous immunoglobulin (IVIG) plus prednisolone for initial therapy for Kawasaki disease (KD) prevented coronary artery abnormalities (CAA) more effectively than IVIG alone. However, questions remain as to whether PSL has potential benefit in all KD patients. The present study was designed to explore the possibility of stratified initial therapy including PSL in patients with and without a high predicted risk of being an IVIG nonresponder. Methods: We retrospectively analyzed data from KD patients who received IVIG (n = 896) or IVIG + PSL (n = 110) by scoring the likely risk of being an IVIG nonresponder. We compared clinical and coronary outcomes between treatment-defined groups separately for high- and low-risk patients. Results: Among low-risk patients (score 0–4), clinical and coronary outcomes were similar. Among high-risk patients (score 5 or more), incidences of treatment failure and coronary artery abnormalities until 1-month follow-up were more frequent in the IVIG than in the IVIG + PSL group. Sex- and score point-adjusted odds ratios for IVIG + PSL were 0.17 (95% confidence interval, 0.08–0.39) for treatment failure and 0.27 (95% confidence interval, 0.07–0.85) for coronary artery abnormalities A among high-risk patients. Conclusions: IVIG + PSL treatment was associated with improving clinical and coronary outcomes in patients at high risk of being IVIG nonresponders.

Magnetic resonance coronary angiography to evaluate coronary arterial lesions in patients with Kawasaki disease.

We evaluated the efficiency of non-invasive magnetic resonance coronary angiography in detecting coronary arterial lesions in 106 patients, aged from 4 months to 37 years, with a median of 13 years, with Kawasaki disease. Non-contrast enhanced, free-breathing magnetic resonance coronary angiographic studies using both the steady-state free precession technique, namely bright blood imaging, and navigator-echo proton density weighted black blood imaging, so-called black blood imaging, were performed in all the patients. Conventional X-ray coronary angiography was performed in 70 patients with coronary arterial lesions. We observed 97 aneurysms, 17 dilatations, 17 occlusions, 18 localized stenoses and 10 recanalized vessels, and we clarified their unique pattern of images on magnetic resonance coronary angiography. The differences in size of the aneurysms as seen on X-ray coronary angiography and bright blood imaging was mean 0.0, and the 95% confidence interval was from -1.4 to 1.5 on the Bland-Altman plots. With bright blood imaging, the sensitivity of occlusion and localized stenosis based on X-ray angiography was 94.2% and 97.2%, specificity was 99.5% and 97.2%, and negative-predictive value was 99.5% and 97.2%, respectively. Black blood imaging provided remarkable visualization of the thickened intima of aneurysms, and/or thrombus, in 38 lesions. We conclude that magnetic resonance coronary angiography can visualize all types of lesions due to Kawasaki disease in patients of all ages, and that it is useful to reduce the number of times X-ray angiography needs to be performed in patients with Kawasaki disease.

Possible Synergic Effect of Angiotensin-I Converting Enzyme Gene Insertion/Deletion Polymorphism and Angiotensin-II Type-1 Receptor 1166A/C Gene Polymorphism on Ischemic Heart Disease in Patients with Kawasaki Disease

ACE I/D and AT1R 1166A/C polymorphisms are considered to comprise individual risk factors for the development of coronary disease. We sought to demonstrate that the ACE I/D and AT1R 1166A/C polymorphisms affect coronary artery stenosis in patients with Kawasaki disease (KD). We examined 147 healthy controls and 281 Japanese children with KD. The patients were further divided into group N (n = 246, no ischemia) and group I (n = 35, severe coronary artery stenosis with myocardial ischemia), and we studied the genotype of ACE I/D and AT1R 1166A/C polymorphisms. We also examined ACE activity in patients with acute KD. We did not detect any prevalent genotypes of the ACE and AT1R polymorphisms between controls and KD patients. However, the prevalence of the D allele in the ACE polymorphism and of the C allele in the AT1R polymorphism tended to be higher in group I than in group N (odds ratios, 2.00 and 2.32, respectively). In addition, the presence of the D and/or C alleles significantly increased the relative risk of developing myocardial ischemia (odds ratio, 2.71; p = 0.038). During the convalescent phase of KD, ACE activity was increased despite significant attenuation during the acute phase. These results suggested that the renin-angiotensin system is associated with the formation of severe coronary artery stenosis and myocardial ischemia.

Utility of Coronary MR Angiography in Children with Kawasaki Disease

OBJECTIVE Although coronary arterial lesions due to Kawasaki disease (KD) should be evaluated as early as possible after the acute phase, conventional X-ray coronary angiography poses high risks for young children with the disease. The use of noninvasive MR coronary angiography is desirable, although it is difficult to produce clear images in young children. We developed a method to improve the quality of MR coronary angiography in young children. MR coronary angiography with vector electrocardiogram gating, real-time navigator-echo, 3D, steady-state free precession was performed in 35 children with KD. Many parameters (i.e., field of view, acquisition delay, turbo-field echo-factor, navigator window, and resolution) were optimized for each patient. CONCLUSION Optimization resulted in the acquisition of high-resolution and highsignal images of the coronary arteries. It remarkably improved not only the quality of the images, but also the detection rate of coronary artery segments. MR coronary angiography is a useful method for evaluating coronary aneurysms from the early stages of KD, even in infants and small children.

NASOPHARYNGEAL COLONIZATION WITH HAEMOPHILUS INFLUENZAE TYPE B AMONG INFANTS AND CHILDREN IN JAPAN

Healthy carriers of Haemophilus influenzae type b (Hib) play an important role in the spread of invasive Hib disease. The aim of the present study was to estimate Hib colonization among infants and children in Japan. Specimens from throat and nasopharyngeal cultures were obtained by thorough swabbing of both tonsils and the posterior pharynx. Specimens were inoculated on Hib antiserum agar. This was prepared with Levinthal base and Hib antiserum. Conventional methods were used concomitantly. Four of 474 infants from 1–48 months of age (0.84%) had Hib cultured from their nasopharynx. The carriage rate in 1–12 month old infants was 0.62% (2/322 cases), and that in 13–48 month old children was 1.32% (2/152 cases). Five of 167 (3.0%) 13‐year‐old children, and five of 154 (3.2%) 9‐year‐old children were asymptomatic carriers. Thirty‐five of 104 household contacts of a patient with invasive Hib disease (33.6%) had Hib colonization. The carriage rate in healthy Japanese children may not be different from that in the USA prior to the availability of the conjugate Hib vaccine. The Hib carriage rate in household contacts of patients with invasive Hib disease was higher than in healthy children (P < 0.005). Our results suggest the possibility of an outbreak of invasive Hib disease in Japan.

Serum alanine aminotransferase concentrations in patients with Kawasaki disease.

The distribution of serum alanine aminotransferase (ALT) in patients with Kawasaki disease (KD) was observed by using data collected from a nationwide survey in Japan. In comparison with normal values of 1 to 49 IU/l ALT, the odds ratio of cardiac disorders developing in the KD patients with an ALT of 200 IU/l or more was 1.91 (95% confidence interval, 1.44 to 2.54). The elevation of the ALT in KD patients is associated with the development of cardiac disorders.

The Incidence of Coronary Artery Abnormality in Incomplete Kawasaki Disease

Purpose: To clarify the incidence of coronary artery abnormality (CAA) among incomplete (atypical) Kawasaki disease.Method: We defined incomplete cases as follows. The incomplete Kawasaki disease of narrow definition (nd-IKD) consists of cases with 4 items of principal symptoms without CAA, and cases with less than 4 items of principal symptoms regardless of CAA. The broad definition of incomplete Kawasaki disease (bd-IKD) consists of cases with less than 5 items of principal symptoms regardless of CAA. About 48,000 cases of Japanese nationwide Kawasaki disease survey were analyzed using our criteria. The proportion, age distribution and the incidence of CAA of incomplete cases were compared with that of typical cases with 5 to 6 items of principal symptoms. Result: The proportion of typical cases, bd-IKD and nd-IKD were 85.0%, 15.0% and 11.5%, respectively. The frequency of incomplete cases was slightly higher among the age groups of less than 1 year and over 5 year. The incidence of acute phase CAA among typical cases, bd-IKD and nd-IKD were 19%, 20% and 5%, respectively. The incidence of CAA of 30th illness day among typical cases, bd-IKD and nd-IKD were 12%, 11% and 2%, respectively. Discussion: Although the proportion of CAA in nd-IKD was smaller than that of typical cases, the proportion of CAA in bd-IKD was almost same as that of typical cases. Therefore the same treatment is required for the cases with less than 5 items of principal symptoms. The revision of diagnostic guideline may be necessary when the above mentioned evidence is confirmed by precise secondary survey.