Coronary artery lesions of incomplete Kawasaki disease: a nationwide survey in Japan

Incomplete Kawasaki disease (KD) is associated with delayed diagnosis and treatment, which in turn can lead to the development of coronary artery lesions (CALs). The aim of this study was to determine the epidemiological features of incomplete KD compared with complete KD and to identify risk factors for CALs from incomplete KD patients using data from a nationwide survey of 2007–2008 in Japan. A total of 23,263 patients were classified according to the number of principal clinical signs: 80% (n = 18,620) had complete forms of KD, 14.2% had four principal signs, 4.6% had three signs, and 1.2% had only one or two signs. In comparison with complete KD cases, the prevalence of CAL development tended to be larger and the proportion receiving initial intravenous immunoglobulin (IVIG) treatment were significantly smaller in patients with incomplete forms. In addition, hospital attendance after 7 days of illness or later was significantly associated with CAL development in all incomplete groups (OR: 2.52 in total patients with incomplete KD, 3.26 in those with one or two principal signs, 2.94 in those with three signs, 2.35 in those with four signs). Conclusion The higher prevalence of CALs in incomplete KD reflects difficulties in diagnosis and delays in treatment. More timely diagnosis and treatment of incomplete KD patients could further prevent the development of cardiac lesions.     

Neonatal Kawasaki disease: case report and data from nationwide survey in Japan

Kawasaki disease (KD) is a systemic vasculitis that develops during childhood, with a peak incidence from 6 to 23 months of age. KD also affects younger children, including neonates. We herein describe the case of a 22-day-old patient with incomplete KD. Some characteristics of neonatal KD are also presented with a review of nationwide surveys of KD in Japan involving approximately 130,000 patients during a 12-year period. The surveys identified 23 neonatal cases, accounting for 1/5,500 of patients of all ages with KD. We found that the characteristics of neonatal KD are likely to be incompatible with the classic criteria for KD and that the incidence of coronary disorders in neonatal patients was not statistically higher than that in older patients. These findings are very similar to those of previous reports of neonatal KD. Conclusion: Neonatal KD is rare and often presents with only a few features of KD. In addition, both neonatal and older patients with KD are at risk of coronary disorders. These characteristics present a challenge to pediatricians in the diagnosis and treatment of febrile neonates.     

Leukocyte counts in patients with Kawasaki disease: from the results of nationwide surveys of Kawasaki disease in Japan

In the latest survey of Kawasaki disease in Japan, questionnaires on maximal leukocyte counts of the patients were included to clarify whether leukocyte counts could be of value for the diagnosis and prediction of outcome. A questionnaire form and diagnostic guidelines for Kawasaki disease were sent to all pediatric departments of hospitals with ≥100 beds throughout Japan, and information including maximal leukocyte counts was obtained on patients with Kawasaki disease diagnosed during the 2-y period from January 1993 to December 1994. Of the 11 458 patients diagnosed during the 2-y period, maximal leukocyte counts were reported in 11 062 patients (96.5%). The mean value and the distribution of maximal leukocyte counts were lower in the age group under 1 y. The mean values and the distribution of leukocyte counts were lowest in suspected cases among three diagnostic categories: typical cases of Kawasaki disease, atypical cases, and suspected cases. The mean values of maximal leukocyte counts of the patients with cardiac sequelae were significantly higher than those without cardiac sequelae in each age group. The proportion of patients with cardiac sequelae increased with leukocyte counts in each age group. The Receiver/Response Operating Characteristic (ROC) curve for maximal leukocyte counts in Kawasaki disease revealed that the accuracy of maximal leukocyte counts for prediction of cardiac sequelae was highest in the age group <6 months, and the most accurate cut-off point was 16 × 10⁹/l. The strongest association between higher leukocyte counts (≥16 × 10⁹/l) and cardiac sequelae was observed in the age group <6M. A large-scale analysis of leukocyte counts in patients with Kawasaki disease revealed age-dependent relationship between maximal leukocyte counts, diagnostic categories and outcome. Maximal leukocyte counts may be helpful for the prediction of outcome with the consideration of age.     

Isolated hypoganglionosis: results of a nationwide survey in Japan

Purpose

This study analyzes how isolated hypoganglionosis (IH) is diagnosed and treated in Japanese pediatric surgical departments.

Methods

A second questionnaire was sent to 90 pediatric surgical departments that took part in an initial survey on variant Hirschsprung’s disease.

Results

Of 109 cases registered as having a certain diagnosis of IH, we targeted 90 patients and excluded the remaining 19. Symptom onset was neonatal ileus with a male:female ratio of 34:56. In most cases, results from radio-contrast enemas and suction rectal biopsies were normal. Anorectal manometry demonstrated that there was no relaxation in 73 % of the 37 patients examined. Furthermore, out of 55 patients who were examined intraoperatively, IH was diagnosed or suspected in 29 cases. Another 12 cases were eventually diagnosed with IH by other institutions using paraffin-embedded specimens. Stomas were initially created in 89 out of 90 cases and the mortality rate of the group that initially received jejunostomies was significantly lower than that of the ileostomy group (p < 0.05).

Conclusion

Preoperative diagnosis of IH is often difficult and intraoperative biopsies were only able to provide a correct diagnosis in 52 % of cases. More accurate diagnosis and the initial creation of jejunostomies rather than ileostomies may assist in improving patient management and outcomes.     

Early intravenous gamma-globulin treatment for Kawasaki disease: the nationwide surveys in Japan

OBJECTIVE: To determine the optimal period of intravenous gamma-globulin (IVGG) treatment, using the database from nationwide Kawasaki disease surveys in Japan. STUDY DESIGN: We selected patients who first visited a doctor within 3 days of illness and received IVGG treatment within 9 days of illness. We divided these patients into 2 groups: an early group (treated on days 1-4: 4731 cases) and a conventional group (days 5-9: 4020 cases). We compared the rate of additional IVGG and prevalence of cardiac sequelae between these groups. RESULTS: The rate of additional IVGG in the early group was significantly higher than those of the conventional group (OR, 1.12 [95% CI, 1.10-1.16]). There were no significant differences in cardiac sequelae between the two groups. CONCLUSIONS: There is no evidence that IVGG treatment on day 4 or earlier has greater efficacy in preventing cardiac sequelae than treatment on days 5 to 9. In addition, early treatment is likely to result in a greater requirement for additional IVGG. However, there is also no evidence that early treatment increases the prevalence of cardiac sequelae in a clinical practice setting, where additional IVGG can be given to those whose initial treatment fails.     

Incidence rate of recurrent Kawasaki disease and related risk factors: from the results of nationwide surveys of Kawasaki disease in Japan

To investigate the incidence of recurrent Kawasaki disease, and to discuss some of the potential risk factors, data of the 13th and 14th nationwide surveys of Kawasaki disease in Japan were analyzed. To calculate the rate of recurrence, 10 679 patients with 31 501.9 person-years were observed. The mean observation period was 2.95 y. The rate of recurrence was 6.89 per 1000 person-years, with a high incidence within the 12 mo following the first episode. Conclusion: The incidence was high among those under 3 y of age and those with cardiac sequelae during the first episode. None of the other factors affected the incidence.     

Nationwide survey on Kawasaki disease in Japan

Results of the statistical analysis of a nationwide survey of patients with Kawasaki disease diagnosed within a 2-year 6-month period, from July 1982 to December 1984, are as follows. (1) The cumulative number of patients reported by the end of 1984 was 63,399 (36,891 boys and 26,508 girls; male to female ratio 1.4). (2) There were two epidemic years, 1979 and 1982, in which the numbers of patients were more than twofold that of the previous years. (3) A curve plotted for age-specific incidence rate showed a unimodal peak at age 1 year. (4) Steroid therapy was used for 6.3% of the patients, aspirin for 89.8%, antibiotics for 57.6%, and gamma-globulin for 11.4%. (5) The proportion of sibling cases was 1.4% and that of recurrent cases was 3.9% of all cases reported. (6) The incidence of cardiac sequelae in 1 month after disease onset was 17.2%.     

Increasing incidence of Kawasaki disease in Japan: Nationwide survey

Background: The last nationwide survey of Kawasaki disease in Japan was conducted in 2003; the epidemiologic features of the disease in Japan since then are unknown.
Methods: All the hospitals with a pediatric department and a bed capacity of ≥100, or hospitals having a bed capacity of <100 but specializing in pediatrics in Japan were asked to report (by mail) all patients with Kawasaki disease who visited the hospital due to the disease in 2003 and 2004.
Results: Of the 2335 hospitals asked to participate, 1058 reported 19 138 patients with Kawasaki disease during the 2 year period 2003–2004. The annual incidence in 2004 reached 174.0 per 100 000 children under 5 years of age. The yearly number of patients and annual incidence increased significantly after the last nationwide epidemic of the disease in 1986. The number of patients was largest in January and lowest in October. The age-specific incidence was highest for those aged 9–11 months, and 88.9% of the patients were under 5 years of age. Of the reported patients, 2595 (13.6%) had cardiac lesions in the acute phase of the disease and 844 (4.4%) had cardiac sequelae 1 month after the onset of the disease.
Conclusion: The number of patients and the incidence of Kawasaki disease in Japan has increased year by year in the last two decades.     

Hospital facilities available to patients with Kawasaki disease: Results of a national survey of Kawasaki disease in Japan

Since 1970, thirteen nationwide epidemiologic surveys of Kawasaki disease have been conducted, and questions on the current situation of hospitals and their facilities have been included in the survey form to assess the care available to patients with Kawasaki disease. To clarify the characteristics of medical care for Kawasaki disease, this paper summarizes the present condition of hospital facilities available to patients with Kawasaki disease. A questionnaire form including questions about the situation of hospital facilities was sent to all pediatric departments of hospitals with 100 or more beds throughout Japan. The proportion of hospitals in which successive observations with echocardiography (UCG) is available (UCG available hospital) was significantly increased compared with the ninth survey (1985–86), whereas that of the hospitals in which coronary angiography (CAG) is available (CAG available hospital) was significantly decreased. Almost all (96.2%) of the patients were reported from the UCG available hospitals. The proportion of patients reported from hospitals with a set policy for intravenous gamma globulin (IVGG) therapy was 74.5%. The proportion of UCG available and CAG available hospitals and that of hospitals with a set policy for IVGG therapy correlated with the increase in the number of patients. In conclusion, hospital facilities available to patients with Kawasaki disease in Japan have satisfactory capability for diagnosis and management of Kawasaki disease.     

Pentoxifylline and intravenous gamma globulin combination therapy for acute Kawasaki disease

We compared the efficacy of oral administration of pentoxifylline (PTX) and intravenous infusions of gamma globulin (IVGG) combination therapy with that of IVGG in reducing the frequency of coronary-artery lesions (CAL) in children with Kawasaki disease (KD), in a randomized trial. All patients with KD received acetylsalicylic acid (30 mg/kg per day), until the 30th day, after the onset of fever, followed by daily acetylsalicylic acid at a dose of 3-5 mg/kg per day there-after, and intravenous IVGG, 200 mg/kg per day, for 5 consecutive days. In addition, patients randomly assigned to PTX and IVGG combination therapy groups received oral PTX at a dosage of 10 mg/kg per day (low-dose) or 20 mg/kg per day (high-dose), in three divided doses until the 30th day. Patients with KD were all free from CAL prior to treatment. We assessed the presence of CAL by two-dimensional echocardiography which was also done prior to treatment and then twice a week after hospital admission. We detected CAL in 3 of 18 patients (16.7%) in the IVGG therapy group, as compared with 2 of 18 patients (11.1%) in the low-dose PTX and IVGG combination therapy group. There were no significant differences between the two groups. In the next study, we detected CAL in 3 of 21 patients (14.3%) in the IVGG therapy group, as compared with none of 22 patients (0%) in the high-dose PTX and IVGG combination therapy group (² = 6.4, P < 0.02). No adverse side-effects were observed in 79 patients with KD.     

对大剂量静脉丙种球蛋白初治无效的川崎病的处治及相关因素探讨

目的　大剂量静脉丙种球蛋白已成为川崎病治疗常规方法 ,但有部分患儿治疗无效 ,该文探讨对大剂量静脉丙种球蛋白 (IVIG)初治无效的川崎病的处治及相关因素。方法　对 1 994年 1月至 2 0 0 2年 1 2月该院收治的对大剂量IVIG初治无效的川崎病 1 4例予附加治疗 :重复IVIG和 /或皮质激素。对初治有效 (5 0例 )和无效 (1 4例 )的两组川崎病患儿的年龄、治疗前热程及实验室数据 ,进行统计分析。结果　 1 4例对大剂量IVIG初治无效的川崎病患儿 ,8例对IVIG复治有效 ,5例最后采用皮质激素治疗均有效 ,3例冠脉扩张者好转。统计分析 ,初治无效病儿发病年龄小 ,血白细胞、乳酸脱氢酶高 ,血红蛋白、白蛋白低 (P <0 .0 5 ) ,冠脉扩张发生率高 (6 / 1 4比5 / 5 0 )。结论　大剂量IVIG初治无效的川崎病者采用附加治疗对病情控制和改善冠脉扩张有效。对于川崎病患儿进行年龄、热程、实验室数据分析 ,有助于采取及时、积极有效的治疗。     

Neonatal gastrointestinal perforation in Japan: a nationwide survey

Purpose

The purpose of this study is to identify the current clinical features of neonatal gastrointestinal perforation in Japan.

Methods

A questionnaire about cases of neonatal gastrointestinal perforation treated in recent 5 years was sent to participating institutions of the Japanese Society of Pediatric Surgeons (JSPS).

Results

Five hundred and thirty-six neonates with gastrointestinal perforation were treated. They consisted of 42 patients with gastric rupture/perforation (GR), 33 patients with intestinal atresia/stenosis (IA), 3 patients with malrotation (ML), 118 patients with necrotizing enterocolitis (NEC), 160 patients with focal intestinal perforation (FIP), 46 patients with meconium-related ileus (MRI), 77 patients with meconium peritonitis (MP), and 57 patients with other conditions. The total mortality rate was 20.5 %. The mortality rates of the patients with GR, IA, ML, NEC, FIP, MRI, and MP were 9.5, 9.1, 0, 33.1, 20.6, 28.2, and 9.1 %, respectively. In 263 cases involving extremely low-birth-weight neonates (ELBW), 108 died (mortality rate 41.1 %). The mortality rates for ELBW with GR, NEC, FIP, MRI, MP, and other conditions were 27.3 % (3/11), 58.5 % (48/82), 21.6 % (24/111), 70.6 % (24/34), 57.1 % (4/7), and 27.8 % (5/18), respectively.

Conclusions

The mortality rates for ELBW decreased from 62.8 % in the previous survey to 41.1 % by the time of this survey.

     

Incidence of Kawasaki disease in Japan: the nationwide surveys of 1999–2002

BACKGROUND: The purpose of the present study was to describe the results of nationwide epidemiologic surveys of Kawasaki disease for the 4 year period 1999-2002. METHODS: The design is a retrospective incidence survey. The patients reported in these two surveys are all new patients who were reported during the two study periods (1999-2000 and 2001-2002), although the data were collected retrospectively. A questionnaire was sent to all pediatric departments of hospitals with 100 beds or more throughout Japan, requesting data on patients with Kawasaki disease, such as sex, age, date of first hospital visit, recurrence, and cardiac lesions. RESULTS: The total number of patients reported in the 4 year period 1999-2002 was 32 266 (18 604 male, 13 662 female), with an average annual incidence of 137.7 per 100 000 children younger than 5 years old. The male/female ratio was 1.30. The incidence peaked at 9-11 months of age, and the proportion of patients under 1 year of age was 26%. The monthly distribution had a high peak in January and a gradual increase in summer. Geographically, the high-incidence areas were limited to certain prefectures and moved from year to year. The cardiac lesions at acute stage and cardiac sequelae occurred more in children under 1 year and older than 4 years. Among the principal symptoms, fever persisting >or=5 days occurred most commonly, followed by conjunctival congestion, changes in lips and oral cavity, polymorphous exanthema, and changes of extremities. Cervical lymphadenopathy occurred less. CONCLUSION: More than 32 000 patients with Kawasaki disease during the 4 year period 1999-2002 were reported to the nationwide incidence surveys. The number of patients is steadily increasing despite the decrease of children. The seasonal variation, geographical distribution, and age-specific distribution support the infection theory for the etiology of Kawasaki disease.     

Prevention of giant coronary artery aneurysms in Kawasaki disease by intravenous gamma globulin therapy

Previous studies have demonstrated the efficacy of intravenous gamma globulin in the prevention of coronary artery abnormalities in Kawasaki disease. We retrospectively reviewed our single-hospital experience with patients in whom Kawasaki disease was diagnosed from January 1979 to July 1987. Only 3 of 68 (4%) patients treated with intravenous gamma globulin in the first 10 days of illness developed coronary artery abnormalities (one of the three had abnormalities before gamma globulin therapy), in comparison with 39 of 119 (33%) patients not treated with gamma globulin (p less than 0.001). Giant coronary artery aneurysms, which are associated with the greatest morbidity and mortality rates in Kawasaki disease, developed in none of the 68 patients treated with gamma globulin but in 7 of 119 patients (6%) not treated with gamma globulin (p = 0.04). Intravenous gamma globulin appears to be effective not only in reducing the overall prevalence of coronary artery abnormalities in Kawasaki disease but, more important, in preventing the formation of giant aneurysms, the most serious form of coronary abnormality after this illness.     

Clinical trial of single-dose intravenous gamma globulin in acute Kawasaki disease. Preliminary report

Gamma globulin administered in a single dose of 1 g/kg of body weight intravenously caused prompt clinical improvement in 27 of 32 consecutive children with Kawasaki disease treated by the 12th day of illness. Response was equally good for the 20 children treated in the first week and the 12 treated in the second week. Fever and clinical signs abated within the first day after treatment, the mean white blood cell count normalized by 48 hours, and the sedimentation rate continued to be elevated for about 2 weeks, while the platelet count rose during the first 2 weeks after treatment and returned to normal approximately 1 month after treatment. Five children with incomplete relief needed more than the single dose before resolution of signs and symptoms occurred. Coronary aneurysms in 2 patients before treatment regressed by 2 weeks. No patient developed coronary aneurysms. No child had sequelae of Kawasaki disease at a follow-up of 2 to 31 months. We believe that although this was a one-arm, uncontrolled pilot study, the results suggest that this protocol provides a safe, flexible, and effective treatment for acute Kawasaki disease.