No full-text available
To read the full-text of this research,
you can request a copy directly from the author.
Maladie de Kawasaki
Résumé
La maladie de Kawasaki est une maladie rare qui touche particulièrement les nourrissons et les jeunes enfants décrite pour la première fois dans les années 60. Il s’agit d’une vascularite aiguë fébrile qui affecte notamment les artères coronaires. Elle représente la première cause de cardiopathie acquise chez l’enfant. En fonction de la combinaison des symptômes, on observe des formes complètes ou incomplètes de la maladie de Kawasaki. Le diagnostic de la maladie de Kawasaki étant uniquement clinique avec des symptômes non spécifiques et sans marqueur biologique, on observe souvent un retard au diagnostic. La complication majeure et redoutée est une atteinte cardiaque par anévrisme des artères coronaires alors qu’il existe un traitement diminuant le risque de survenue d’anévrisme coronarien. N’ayant aucune expérience dans la conception d’un enseignement par le moyen du e-learning, l’objectif de cet article est de présenter les étapes de conception du e-learning sur la maladie de Kawasaki, les difficultés rencontrées et l’outil final afin de permettre à d’autres personnes d’utiliser ce nouvel outil de communication et méthode pédagogique.
We report 101 episodes of Kawasaki disease in 100 patients seen over a 12 year period. A total of 35 patients had cardiac involvement ranging from pericardial effusion to coronary artery aneurysms with ischaemic complications, which resulted in death in one patient. Laboratory investigations showed leucocytosis, thrombocytosis, and a raised erythrocyte sedimentation rate to be common features and the first two variables were significantly associated with cardiac involvement. Treatment regimens changed over the study period. Aspirin was used in most patients often in conjunction with dipyridamole and from 1986 intravenous immunoglobulin was given routinely to those patients seen early in the illness. Additional therapeutic measures in individual patients included prostacyclin, heparin, streptokinase, and plasma exchange/exchange transfusion. Attention is drawn to the uncertainity of the long term cardiovascular consequences in the light of adults reported with premature atherosclerotic lesions of similar appearance to those seen in Kawasaki disease.
To determine the prevalence of Kawasaki disease in older children and to evaluate its clinical presentation, time to diagnosis, and outcome in comparison with younger patients with the disease.
A retrospective analysis of all patients discharged with a diagnosis of Kawasaki disease at a pediatric tertiary care hospital over a 12-year period.
A total of 133 patients were included in this study; 7.5% were 9 years of age or older at the time of illness. Patients were grouped by age: infants included children age 1 to 8 years of age and children 9 years of age or older. Older children had a higher frequency of abnormal cardiovascular physical examination (50%) versus children (6%) and infants (10%). The older age group and the infants had a higher prevalence of coronary artery abnormalities and poor left ventricular function than did the 1- to 8-year-olds. Eighty percent of the older children had coronary arteries that were either dilated or aneurysmal, and 30% demonstrated left ventricular dysfunction on initial echocardiography. The number of days to diagnosis after meeting the diagnostic criteria was 5.8 +/- 2.3 for infants, 5.2 +/- 1.5 for older children, and 1.9 +/- 0.3 for children. Older children had a complicated course of Kawasaki disease compared with younger patients.
We found a higher prevalence of older children with Kawasaki disease at our center than has previously been reported. Older patients, as well as infants, had a higher rate of coronary artery abnormalities than did the children between 1 and 8 years of age. Older age at the time of illness or a delay in treatment may be important factors in determining cardiac involvement in Kawasaki disease.
To evaluate the epidemiologic pattern of Kawasaki disease (KD) in the United States over 10 years.
The National Inpatient Sample, a stratified national sample of >900 hospitals in 22 states of the United States, was used. Data on hospital discharges from 1988-1997 were analyzed. Patients <18 years of age with a discharge diagnosis of KD were identified.
There were 6442 patients with KD admitted to 651 hospitals. Median age at hospital admission was 2 years. Peak incidence by year of age was 1 year old. Children <2 years old accounted for 36.6% of all cases; <5 years old, 75.6%; and <10 years old, 95.6%. The age distribution seems to be wider than reported from Japan. The incidence for children <5 years old was 8.1 per 100 000 people in 1988, and increased to 18.5 in 1997. There were 3905 males (60.6%) and 2537 females (39.4%), for a male-to-female ratio of 1.54. The incidences were higher in winter and spring (December to May) and dropped to a nadir between July and September. No apparent change in seasonal pattern was noted over 10 years. The South census region showed a seasonal change 2 to 3 months ahead of other regions. The overall in-hospital mortality rate was 0.17%. The mortality rate in children > or =10 years (1.4%) was significantly higher in than children <10 years (0.11%).
KD affects mainly children under 5 years of age, with a peak incidence in children 1 to 2 years of age. The incidence of KD was rising over the study period. There is a male predominance. Although KD occurs year-round, the lowest incidence is seen from July through September. Such seasonal variation did not change over the 10 years. Seasonal pattern may vary in different geographic regions. Mortality from KD is rare, although children > or =10 years are at higher risk.
This article reviews the clinical features, epidemiology, laboratory findings, pathology, differential diagnosis, etiology, pathogenesis, and treatment of acute febrile mucocutaneous lymph node syndrome (MCLS), otherwise known as Kawasaki's disease. It is concluded that although overlap exists between MCLS and other acute diseases, it appears to be a distinct clinical entity. The etiology is still not established, and at the present there is no accepted treatment, although suppression of accelerated platelet aggregation seen in MCLS by using aspirin or flurbiprofen has been advocated. There are 115 references.
• The occurrence of a distinctive perineal eruption that appears in infants and children early in the course of Kawasaki syndrome has received little attention in the medical literature. Medical records of patients hospitalized during the acute phase of Kawasaki syndrome were reviewed to evaluate the prevalence of an erythematous, desquamating perineal eruption. The frequency of this eruption was compared with the syndrome's other diagnostic criteria. Thirty-nine (67%) of the 58 patients who fulfilled the criteria for the diagnosis of Kawasaki syndrome had documentation of the perineal rash that usually occurred in the first week of onset of symptoms. No statistically significant differences were found in the frequency of coronary artery aneurysms. We believe that an erythematous, desquamating perineal rash is a valuable early clinical finding facilitating a more rapid diagnosis and treatment of Kawasaki syndrome.
(Arch Dermatol 1988;124:1805-1810)
Kawasaki disease (KD) is an acute multisystem vasculitis of unknown etiology that is associated with marked activation of T cells and monocyte/macrophages. Using a quantitative polymerase chain reaction (PCR) technique, we recently found that the acute phase of KD is associated with the expansion of T cells expressing the V beta 2 and V beta 8.1 gene segments. In the present work, we used a newly developed anti-V beta 2 monoclonal antibody (mAb) and studied a new group of KD patients to extend our previous PCR results. Immunofluorescence analysis confirmed that V beta 2-bearing T cells are selectively increased in patients with acute KD. The increase occurred primarily in the CD4 T cell subset. The percentages of V beta 2+ T cells as determined by mAb reactivity and flow cytometry correlated linearly with V beta expression as quantitated by PCR. However, T cells from acute KD patients appeared to express proportionately higher levels of V beta 2 transcripts per cell as compared with healthy controls or convalescent KD patients. Sequence analysis of T cell receptor beta chain genes of V beta 2 and V beta 8.1 expressing T cells from acute KD patients showed extensive junctional region diversity. These data showing polyclonal expansion of V beta 2+ and V beta 8+ T cells in acute KD provide additional insight into the immunopathogenesis of this disease.
Background— Kawasaki disease is an acute self-limited vasculitis of childhood that is characterized by fever, bilateral nonexudative conjunctivitis, erythema of the lips and oral mucosa, changes in the extremities, rash, and cervical lymphadenopathy. Coronary artery aneurysms or ectasia develop in ∼15% to 25% of untreated children and may lead to ischemic heart disease or sudden death.
Methods and Results— A multidisciplinary committee of experts was convened to revise the American Heart Association recommendations for diagnosis, treatment, and long-term management of Kawasaki disease. The writing group proposes a new algorithm to aid clinicians in deciding which children with fever for ≥5 days and ≤4 classic criteria should undergo echocardiography, receive intravenous gamma globulin (IVIG) treatment, or both for Kawasaki disease. The writing group reviews the available data regarding the initial treatment for children with acute Kawasaki disease, as well for those who have persistent or recrudescent fever despite initial therapy with IVIG, including IVIG retreatment and treatment with corticosteroids, tumor necrosis factor-α antagonists, and abciximab. Long-term management of patients with Kawasaki disease is tailored to the degree of coronary involvement; recommendations regarding antiplatelet and anticoagulant therapy, physical activity, follow-up assessment, and the appropriate diagnostic procedures to evaluate cardiac disease are classified according to risk strata.
Conclusions— Recommendations for the initial evaluation, treatment in the acute phase, and long-term management of patients with Kawasaki disease are intended to assist physicians in understanding the range of acceptable approaches for caring for patients with Kawasaki disease. The ultimate decisions for case management must be made by physicians in light of the particular conditions presented by individual patients.
• Kawasaki syndrome (KS) is an idiopathic, acute, febrile, exanthemous illness that primarily affects infants and children. We describe a 20-year-old black woman who fulfilled the clinical criteria for the diagnosis of KS and excluded other possible causes. In addition, we reviewed data on 21 patients with adult KS reported in the English literature and accepted ten cases as representing this syndrome. The epidemiologic, clinical, laboratory, and pathologic features of the 11 cases representing adult KS are discussed. Although the initial reports of adult KS in the United States may have actually represented toxic shock syndrome, the occurrence of KS in adults should be acknowledged.
(Arch Dermatol 1987;123:1356-1361)
More than a decade ago, Tomisaku Kawasaki, a Japanese pediatrician, described an acute exanthematous disease characterized by persistent fever, mucous membrane hyperemia, cervical lymph node enlargement, and periungal desquamation in 50 infants and children who had been seen during the preceding six-year period at the Japan Red Cross Medical Center in Tokyo.1 Individually the clinical and laboratory features seemed not unlike those of other mucocutaneous syndromes and exanthematous illnesses of childhood, but Kawasaki decided that the constellation of findings was distinctive and constituted a hitherto undescribed clinical entity. The disease was designated mucocutaneous lymph node syndrome (MCLS).1
After this description, numerous cases were reported throughout Japan, and in 1970 the Research Committee of MCLS, supported by the Ministry of Health and Welfare of the Japanese government, was organized.
The primary purpose of this group was to conduct and to coordinate investigations involving the etiology and the clinical, pathological
A multicenter randomized controlled study was carried out to assess the effectiveness of different, doses and kinds of γ-globulin in Kawasaki disease. Gamma globulin lowered the incidence of coronary artery abnormalities. The effect of γ-globulin was dose dependent. The intact type was more effective than the pepsin treated type. To establish the indications for γ-globulin, a study was made of patients who received neither γ-globulin nor indomethacin and who, within nine days of onset of illness, satisfied at least four of the following criteria: (1) WBC: more than 12,000/mm; (2) platelet count: less than 35×104γmm; (3) CRP: more than 3 +; (4) Hct: less than 35%; (5) albumin: less than 3.5 g/dl (6) age: 12 months or less; (7) male sex. This prospective study is continuing. Of 143 children, 73.4% received γ-globulin, and only two demonstrated small dilatations of the coronary arteries in children who did not receive γ-globulin. These guidelines seem satisfactory to establish the indications for γ-globulin in Kawasaki disease.
OBJECTIVE: To determine whether the mortality rate of patients with a history of Kawasaki disease is higher than that of the general population. DESIGN: In a cohort study, 6585 patients with Kawasaki disease were observed from the first medical encounter because of the disease through the end of 1992, or until death. Standardized mortality ratios (SMRs) with 95% confidence intervals (CI) were calculated with vital statistics data of Japan for the control. RESULTS: Of 6585 patients who met the eligibility criteria, 6550 (99.5%) were followed through either the end of the study or the date of death. Nineteen patients (14 male subjects) died during the study period; an overall SMR of 1.56 (95% CI, 0.94 to 2.43) was calculated for the entire study period. The SMR was 1.78 (95% CI, 0.97 to 2.99) for male subjects and 1.16 (95% CI, 0.38 to 2.71) for female subjects. During the acute phase of the disease (the first 2 months after onset), the SMR was higher, particularly in male subjects (SMR, 10.12; 95% CI, 3.72 to 22.07). After the acute phase, however, both boys and girls had low SMRs. Nine of the 19 deaths were caused by Kawasaki disease; there were 2 deaths as a result of congenital anomalies of the circulatory system and 2 subjects died of malignant neoplasms of lymphatic or hematopoietic tissues. CONCLUSIONS: Although the mortality rate among those with a history of Kawasaki disease was elevated in Japan, many of the deaths that caused the elevation occurred during the acute phase of the disease. The mortality rate was not increased after the acute phase of the disease. (J PEDIATR 1996;128:75-81)
The Sixth International Kawasaki Disease Symposium brought together clinicians and researchers from around the world to report and discuss the state of the art related to Kawasaki disease, in the magnificent setting of the Hilton Waikoloa Village Resort, Waikoloa, Hawaii. Registration and participation exceeded previous symposia, with over 120 oral and poster presentations, and several invited and named lectures from leading authorities. The Symposium has alternated its location between Japan and Hawaii.
ObjectivesWe determined the profile of cardiovascular risk factors in children late after Kawasaki disease (KD) and compared it with that of age-matched healthy children.BackgroundConcerns have been raised regarding the possibility of a predisposition of KD to premature atherosclerosis later in life.MethodsA cohort of 102 subjects were studied: 37 KD patients with coronary aneurysms (group I), 29 KD patients with normal coronary arteries (group II), and 36 healthy age-matched children (group III). The fasting total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, apolipoprotein (apo) A-I, apoB, and homocysteine levels were compared among the three groups. In addition, blood pressure and brachioradial arterial stiffness, as determined by pulse wave velocity (PWV), were measured and compared.ResultsGroup I subjects had lower HDL cholesterol (p = 0.016) and apoA-I levels (p = 0.044) and higher apoB levels (p = 0.029) and PWV (p = 0.001) than group III control subjects. Likewise, the apoB levels (p = 0.007) and PWV (p = 0.042) were higher in group II than in III subjects, although their HDL cholesterol (p = 0.54) and apoA-I (p = 0.52) levels were similar. The LDL cholesterol levels were higher in group I and II patients than in controls, although not statistically significant (p = 0.17). Blood pressure and homocysteine levels did not differ among the groups.ConclusionsAn adverse cardiovascular risk profile, as characterized by a proatherogenic alteration of the lipid profile and increased arterial stiffness, occurs in children after KD. The profile is worse in those with than in those without coronary aneurysms.
Kawasaki disease was first reported in 1967 by Japanese pediatrician Tomisaku Kawasaki as an acute febrile syndrome mainly affecting the skin, mucosa, and lymph nodes.1 Although initially recognized as benign, this syndrome was subsequently acknowledged to have a serious complication of coronary artery aneurysm,2 and it has gained the worldwide interest of pediatricians and pediatric cardiologists. The importance of and interest in this disease can be seen in the existence of the unusual publication of the English translation of the first report in Japanese.3 Because Japan is the country where the disease was first observed and the largest numbers of new patients are diagnosed each year, researchers there have been making outstanding efforts to uncover the mystery of this disease. Scientists from other countries have also contributed greatly in this regard despite the underlying difficulties in conducting research due to the limited number of cases compared with Japan. The present review article covers such longstanding efforts and their fruits, with a special focus on the long-term outcome of Kawasaki disease. Although data on the epidemiology, origin, pathophysiology, and treatment of this disease are important for a better understanding of the outcome, they have been reviewed extensively by several previous publications.4–6 Nevertheless, key data on these topics are summarized briefly herein.
### Epidemiology
Kawasaki disease is most prevalent in Japan and in children of Japanese ancestry.5,7–10 A neighboring country, Korea, has the second-largest number of patients,11 which indicates apparent racial factors in the origin of this disease. The most recent published data indicate that the annual incidence of Kawasaki disease in Japan is nearly 140 cases per 100 000 children younger than 5 years of age,7 which is approximately 10 to 20 times higher than that of the United States (≈17 cases per 100 000)9,10 …
Ninety-two patients with Kawasaki disease were treated with five different types of drug therapy: a steroid preparation (prednisolone), aspirin, an antibiotic, a combination of steroid plus aspirin, and a combination of steroid plus warfarin. One to two months after the onset of the disease, coronary angiography demonstrated coronary aneurysms in 20% of cases treated with an antibiotic alone, 64.7% of cases in the steroid-treated group, and 11% of those in the aspirin-treated group.
These findings suggest that the steroid might act adversely to cause a progression of coronary lesions of the disease. The aspirin-treated group did not have a significantly lower incidence of coronary lesions compared with the group treated with an antibiotic alone. But in view of the fact that the direct cause of sudden death of the disease is thrombotic occlusion of a coronary artery, aspirin might act as the effective means for prevention of sudden death due to Kawasaki disease.
A multicenter randomized controlled study was carried out to assess the effectiveness of different, doses and kinds of gamma-globulin in Kawasaki disease. Gamma globulin lowered the incidence of coronary artery abnormalities. The effect of gamma-globulin was dose dependent. The intact type was more effective than the pepsin treated type. To establish the indications for gamma-globulin, a study was made of patients who received neither gamma-globulin nor indomethacin and who, within nine days of onset of illness, satisfied at least four of the following criteria: (1) WBC: more than 12,000/mm; (2) platelet count: less than 35 X 10(4)/mm; (3) CRP: more than 3+; (4) Hct: less than 35%; (5) albumin: less than 3.5 g/dl (6) age: 12 months or less; (7) male sex. This prospective study is continuing. Of 143 children, 73.4% received gamma-globulin, and only two demonstrated small dilatations of the coronary arteries in children who did not receive gamma-globulin. These guidelines seem satisfactory to establish the indications for gamma-globulin in Kawasaki disease.
Kawasaki disease is an acute vasculitis characterized by mucosal inflammation, rash, cervical adenopathy, indurative edema of the hands and feet, and late membranous desquamation of the fingertips. Early cardiac effects include myocarditis (occasionally with congestive heart failure), pericardial inflammation, and, rarely, valve involvement. Coronary artery aneurysms are a long-term concern because coronary thrombosis with myocardial infarction can be a late manifestation. The origin of Kawasaki disease is unknown, but an infectious agent is most likely. Management consists of aspirin for control of fever and inflammatory manifestations and intravenous gamma globulin for the prevention of coronary aneurysm formation. Careful late follow-up is required, especially for patients with persistent coronary abnormalities. Giant aneurysms (greater than 8 mm) are more likely to progress to coronary obstructive disease, and coronary bypass grafts have been required for some patients. Late coronary artery manifestations in patients with mild early coronary dilatation have not been described. However, since long-term epidemiologic studies have not yet been performed, it is prudent to consider childhood Kawasaki disease to be a potential risk factor for coronary disease, especially in atherosclerosis-prone Western societies.
To elucidate the incidence and natural history of valvular heart disease in Kawasaki syndrome, we analyzed patients who were found to have a new heart murmur after the onset of the disease. Among 1215 patients we found 13 (1.1%) with valvular disease (12 with mitral regurgitation and one with aortic regurgitation). We compared these patients with 30 who did not have valvular lesions. The duration of fever was longer and the incidence of coronary artery lesions significantly higher than in those without valvular disease. Heart murmurs disappeared within 2 months after the onset of valvular heart disease in five patients, whereas in another six, all involving valve prolapse, they persisted for 2 years or more. We postulate that two different mechanisms may be responsible for the variation in the duration of valvular heart disease: one, which disappeared spontaneously, was attributed to pancarditis; the other, which persisted, was due to dysfunction in valve and papillary muscles as a result of ischemia.
To investigate the pathogenesis of Kawasaki disease, the effects of intravenous gammaglobulin treatment on circulating cytotoxic antibodies against endothelial cells, in-situ endothelial cell activation, and cytokine production and action were examined. Gammaglobulin treatment did not reduce cytotoxic antibody activity against endothelial cells in six patients tested. Expression of endothelial cell activation antigens (endothelial-leucocyte adhesion molecule-1 [ELAM-1] and intercellular adhesion molecule-1) was detected by means of immunoperoxidase staining in skin biopsy samples from five patients before treatment. Samples were obtained immediately after treatment from six patients; there was no endothelial cell activation in four and the two with persistent activation had persistent fever and mucocutaneous symptoms. Peripheral blood mononuclear cells from ten of sixteen acute Kawasaki disease patients spontaneously secreted high levels of interleukin-1 (IL-1). IL-1 secretion remained high in four gammaglobulin-treated patients in whom coronary artery abnormalities developed but fell to normal in six treated patients who had no coronary artery abnormalities. In cell culture, gamma globulin did not inhibit endothelial cell expression of ELAM-1 in response to IL-1 or tumour necrosis factor. The association between improvement of clinical symptoms and the reduction of cytokine secretion and reversal of endothelial cell activation supports a role for immune-mediated injury to cytokine-induced endothelial cell antigens in the pathogenesis of this disorder.
The rate of second-case Kawasaki disease occurring among 1788 siblings of children with the disease was derived from data obtained from questionnaires mailed to the members of the Japanese Association of Parents of Children With Kawasaki Disease. Within 1 year after the onset of the first case in a family, the overall second-case rate was 2.1% for siblings, as compared to an overall incidence of approximately 0.19% in the general population of children 0 to 4 years of age in Japan in the epidemic year 1982. For siblings younger than 1 year of age, it was 8.4%, and for those between 1 and 2 years of age, it was 9.3%. More than half (54.1%) of the second cases developed 10 days or less after the first cases occurred.
The occurrence of a distinctive perineal eruption that appears in infants and children early in the course of Kawasaki syndrome has received little attention in the medical literature. Medical records of patients hospitalized during the acute phase of Kawasaki syndrome were reviewed to evaluate the prevalence of an erythematous, desquamating perineal eruption. The frequency of this eruption was compared with the syndrome's other diagnostic criteria. Thirty-nine (67%) of the 58 patients who fulfilled the criteria for the diagnosis of Kawasaki syndrome had documentation of the perineal rash that usually occurred in the first week of onset of symptoms. No statistically significant differences were found in the frequency of coronary artery aneurysms. We believe that an erythematous, desquamating perineal rash is a valuable early clinical finding facilitating a more rapid diagnosis and treatment of Kawasaki syndrome.
A case of facial palsy was reported initially in 1974 by Murayama as one of the neurological manifestations in Kawasaki disease. Thereafter, an additional nine case have been documented in Japan. This facial palsy, in the revised "Diagnostic Guideline of Kawasaki Disease" released in 1984, has been added recently as one of the neurological signs and symptoms of Kawasaki disease. This is a report on two cases of Kawasaki disease showing facial palsy with indurative oedema during their clinical course, and also a clinical review of the ten previously reported cases of facial palsy complicating Kawasaki disease.
Kawasaki syndrome (KS) is an idiopathic, acute, febrile, exanthemous illness that primarily affects infants and children. We describe a 20-year-old black woman who fulfilled the clinical criteria for the diagnosis of KS and excluded other possible causes. In addition, we reviewed data on 21 patients with adult KS reported in the English literature and accepted ten cases as representing this syndrome. The epidemiologic, clinical, laboratory, and pathologic features of the 11 cases representing adult KS are discussed. Although the initial reports of adult KS in the United States may have actually represented toxic shock syndrome, the occurrence of KS in adults should be acknowledged.
The diameter of the largest coronary arterial aneurysm was examined in 61 autopsied children with Kawasaki disease. Thirty children died during the acute stage: The largest diameter of the coronary aneurysm was 6 mm or more in 23 who died of coronary heart disease and 4.5 mm or less in 7 who died of myocarditis. Thirty-one children died during the healed stage: The diameter of the largest coronary aneurysm was 8 mm or more in 26, to 8 mm in 3, and 2.5 mm or less (normal) in 2. Two patients without coronary aneurysms died of bacterial infections or accidents. Twenty-nine patients with a coronary aneurysm 6 mm or more in diameter died of coronary heart disease. Twenty-three of 26 children with a coronary aneurysm 8 mm or larger had multivessel coronary aneurysms.
Renal sonographic evaluation of seven patients with mucocutaneous lymph node syndrome were performed and correlated with clinical and laboratory data either supporting or not supporting renal disease associated with this entity. Four of seven patients demonstrated significant elevations of the BUN, creatinine and/or significant proteinuria. These four patients had renal sonographic findings of increased cortical echogenicity, enlarged kidneys and enhanced corticomedullary differentiation. This complication of mucocutaneous lymph node syndrome has heretofore not been noted.
Between 1979 and 1984, 11 patients with myocardial infarction following Kawasaki disease were seen in our hospital. There were seven boys and four girls, aged from 3 months to 6 years. This cardiovascular complication developed in the early stage, from 19 days to 6 months of illness, in all but three patients. Significant clinical symptoms were recognized in only five patients. Two patients died, the conditions of two are well controlled with anticongestive therapy, and the remaining patients are asymptomatic. The diagnosis of myocardial infarction was confirmed by the following clinical findings: typical ECG patterns (10/11), abnormality of the left ventricular wall movement by serial two-dimensional echocardiography (9/10), elevated value of cardiac enzymes (6/6), perfusion defect by thallium 201 myocardial scintigraphy (6/8), and coronary artery occlusion or ventricular aneurysm by angiocardiography (9/9). All patients had markedly dilated and multiple coronary aneurysms during the course of the illness. Because myocardial infarction is frequently associated with the rapidly dilating coronary artery during the acute stage, ECG monitoring, preparation of resuscitation equipment, and use of antithrombotic agents are recommended for those high-risk patients. When a myocardial infarction has been diagnosed, measures including cardiac monitoring, use of vasodilators, inotropic agents, and urokinase may be valuable.
Between June 1, 1979, and May 31, 1984, at The Hospital for Sick Children in Toronto, Kawasaki disease was diagnosed in 163 patients (112 boys, 51 girls, P less than 0.001). Fifteen percent of the children had coronary artery aneurysms. Prior to diagnosis, 24% had been given low doses of aspirin, and 50% acetaminophen. Children with coronary aneurysms had significantly higher temperature during days 10 to 13 of the disease. The febrile phase of the disease was also significantly longer in these children. Coronary artery involvement occurred with equal frequency in boys and girls. There was no significantly greater incidence of coronary artery involvement in infants younger than 1 year of age than in older children. Duration of fever (greater than or equal to 14 days vs less than 14 days) was equally as predictive of the eventual occurrence of coronary aneurysms as the modified Asai score.
To identify risk factors for severe sequelae, analyze disease characteristics, and assess efficacy of intravenously administered immune globulin (IVGG) therapy in infants less than 12 months of age with Kawasaki disease.
Retrospective chart review of children less than 12 months of age with Kawasaki disease between 1980 and 1993.
Of 443 patients with Kawasaki disease, 57 (13%) were less than 1 year of age, including 14 (3%) less than 6 months. Age at onset was a predictor of the development of coronary artery aneurysms (CAA) and of giant (> 8 mm) aneurysms: 11 (79%) of 14 children < 6 months and 17 (44%) of 39 children 6 to 12 months of age acquired CAA (p = 0.06), and 5 (37%) of 14 children < 6 months and 2 (5%) of 39 children 6 to 12 months of age acquired giant CAA (p < 0.01). No specific clinical or laboratory features predicted the development of CAA, which was found in 7 (29%) of 24 patients treated with IVGG by illness day 10 and in 21 (73%) of 29 patients treated after day 10 or never treated with IVGG (p < 0.01). Only 1 (4%) of 24 patients treated by day 10 but 6 (21%) of 29 children treated after day 10 or never treated with IVGG acquired giant CAA (p = 0.01). Persistent (> 1 year) CAA were present in 4 (17%) of 24 IVGG-treated children by day 10 and in 14 (48%) of 29 children not treated by day 10 or never treated with IVGG (p < 0.025). There was no difference in outcome if IVGG was given by illness day 7 or on illness days 8 to 10.
Patients with Kawasaki disease less than 6 months of age are at particularly increased risk of having CAA and giant CAA. Therapy with IVGG, given by illness day 10, is associated with substantial reduction in the frequency of CAA and giant CAA in this high-risk population.
Since 1970, twelve nationwide epidemiologic surveys of Kawasaki disease (KD) have been conducted throughout Japan every two years to describe KD in Japan. By the end of 1992, a total of 116,848 cases were reported. This paper summarizes the statistical analysis of the latest survey for the 2-year period from January 1991 through December 1992.
A questionnaire form and diagnostic guidelines for KD were sent to all pediatric departments of hospitals with 100 or more beds throughout Japan and information was obtained on patients with KD diagnosed during the 2-year period from January 1991 through December 1992.
The summary of the results is: 1) the number of patients reported was 11,221 (6604 males and 4617 females; male/female ratio = 1.43) with a yearly incidence rate of 90 per 100,000 children < 5 years old; 2) the monthly number of patients was higher in winter and summer, although the monthly difference was not marked; 3) age-specific incidence rates showed a unimodal peak at 1 year of age; 4) the proportion of patients with a family history of KD in a sibling was 1%; 5) the proportion of recurrent patients was 3%; 6) the proportion of patients with cardiac sequelae 1 month after disease onset was 13%; and 7) the number of patients who died was 9, which conforms to 0.08% of total patients.
The incidence rates of KD in Japan are ten times higher than those reported in western countries and almost constant over 6 years. The descriptive epidemiology of the disease, which supports the infection theory, does not change for years.
Kawasaki syndrome (KS), the main cause of acquired heart disease in children, is associated with the selective expansion of V beta 2+ T cells in peripheral blood. Our study suggests that KS may be caused by a superantigen--a staphylococcal or streptococcal toxin. Bacteria were cultured without knowledge of their origin, from the throat, rectum, axilla, and groin of 16 patients with untreated acute KS and 15 controls. Bacteria producing toxins were isolated from 13 of 16 KS patients but from only 1 of 15 controls (p < 0.0001). Toxic shock syndrome toxin (TSST) secreting Staphylococcus aureus was isolated from 11 of the 13 toxin-positive cultures, and streptococcal pyogenic exotoxin (SPE) B and C were found in the other 2. These toxins are known to stimulate V beta 2+ T cells. All TSST-producing KS isolates were tryptophan auxotrophs indicating they were clonally related. S aureus isolates from acute KS patients were unusual because they produced less lipase, haemolysin, and protease compared to other isolates (p < 0.01). S aureus colonies from KS patients were white, and could be easily mistaken for coagulase-negative staphylococci, whereas colonies of non-KS isolates were gold. These observations suggest that the expansion of V beta 2+ T cells in most patients with KS may be caused by a new clone of TSST-producing S aureus, and, in a minority of patients, SPEB-producing or SPEC-producing streptococci.
There are 36 reports in the English-language literature of Kawasaki disease in adults. We present two additional cases, in one of which retinal vasculitis developed, a previously unreported complication antemortem. We report the first use of intravenous gamma globulin in the United States for treatment of adult-onset Kawasaki disease and review the pertinent literature.
(Arch Intern Med. 1994;154:1398-1405)
Kawasaki disease (KD) is an acute multisystem vasculitis of unknown etiology that is associated with marked activation of T cells and monocyte/macrophages. Using a quantitative polymerase chain reaction (PCR) technique, we recently found that the acute phase of KD is associated with the expansion of T cells expressing the V beta 2 and V beta 8.1 gene segments. In the present work, we used a newly developed anti-V beta 2 monoclonal antibody (mAb) and studied a new group of KD patients to extend our previous PCR results. Immunofluorescence analysis confirmed that V beta 2-bearing T cells are selectively increased in patients with acute KD. The increase occurred primarily in the CD4 T cell subset. The percentages of V beta 2+ T cells as determined by mAb reactivity and flow cytometry correlated linearly with V beta expression as quantitated by PCR. However, T cells from acute KD patients appeared to express proportionately higher levels of V beta 2 transcripts per cell as compared with healthy controls or convalescent KD patients. Sequence analysis of T cell receptor beta chain genes of V beta 2 and V beta 8.1 expressing T cells from acute KD patients showed extensive junctional region diversity. These data showing polyclonal expansion of V beta 2+ and V beta 8+ T cells in acute KD provide additional insight into the immunopathogenesis of this disease.
A series of 30 cases of Kawasaki disease has been studied retrospectively over a period of 11 years. The aim was to reassess the diagnostic value of the dermatological manifestations. A modification of the extremities was observed in 28 patients (23 had early inflammatory lesions, 25 had late desquamation). Exanthema was constant, polymorphous and most often urticaria-like. Vesicles, pustules or purpura were noted during the course of the eruption in 7 patients. A perineal eruption was observed in 17 cases and was found of good diagnostic value even though not pathognomonic. Cheilitis was the most frequent of buccopharyngeal modifications (93 p. 100). Conjunctival hyperemia was noted in 26 patients. Eight children had cardiovascular complications. Among these cases, the modification of the extremities seemed to be more pronounced and stomatitis and arthritis were apparently more frequent. Most of all, the inflammatory syndrome was significantly more severe as concerns CRP and polymorphonuclear leukocytes counts. Dermatological examination often rules out other diagnoses, such as measles, scarlet fever and staphylococcal toxic shock syndrome. However, a complete etiological workup remains mandatory.
Kawasaki disease is an acute vasculitis of young children that is complicated by the development of myocarditis and coronary artery abnormalities. Recent studies indicate that the prevalence of cardiovascular abnormalities can be significantly reduced by treating patients during the first 10 days of illness with high-dose intravenous gammaglobulin, particularly at a dose of 2 g/kg. Thus, early recognition and prompt treatment of this illness is critical for a successful outcome. This process would undoubtedly be facilitated if the etiologic agent or toxin that causes Kawasaki disease were known. In this regard, studies of the past year strongly suggest that a superantigen plays an important role in stimulating the massive immune activation associated with this illness. These observations may provide an important new direction for investigations into the etiology and pathogenesis of Kawasaki disease.
To determine whether the mortality rate of patients with a history of Kawasaki disease is higher than that of the general population.
In a cohort study, 6585 patients with Kawasaki disease were observed from the first medical encounter because of the disease through the end of 1992, or until death. Standardized mortality ratios (SMRs) with 95% confidence intervals (CI) were calculated with vital statistics data of Japan for the control.
Of 6585 patients who met the eligibility criteria, 6550 (99.5%) were followed through either the end of the study or the date of death. Nineteen patients (14 male subjects) died during the study period; an overall SMR of 1.56 (955 CI, 0.94 to 2.43) was calculated for the entire study period. The SMR was 1.78 (95% CI, 0.97 to 2.99) for male subjects and 1.16 (95% CI, 0.38 to 2.71) for female subjects. During the acute phase of the disease (the first 2 months after onset), the SMR was higher, particularly in male subjects (SMR, 10.12; 95% CI, 3.72 to 22.07). After the acute phase, however, both boys and girls had low SMRs. Nine of the 19 deaths were caused by Kawasaki disease; there were 2 deaths as a result of congenital anomalies of the circulatory system and 2 subjects died of malignant neoplasms of lymphatic or hematopoietic tissues.
Although the mortality rate among those with a history of Kawasaki disease was elevated in Japan, many of the deaths that caused the elevation occurred during the acute phase of the disease. The mortality rate was not increased after the acute phase of the disease.
Kawasaki disease is an acute vasculitis of unknown etiology that predominantly affects children <5 years of age. Structural damage to the coronary arteries after the acute, self-limited illness is detected by echocardiography in approximately 25% of untreated patients. The long-term effects of the acute coronary arteritis are unknown. To define the spectrum of clinical disease in young adults that can be attributed to Kawasaki disease in childhood, we performed a retrospective survey of cases reported in the English and Japanese published data of adult coronary artery disease attributed to antecedent Kawasaki disease. The mean age at presentation with cardiac sequelae was 24.7 +/- 8.4 years (range 12 to 39) for the 74 patients identified with presumed late sequelae of Kawasaki disease. Symptoms at the time of presentation with cardiac sequelae included chest pain/myocardial infarction (60.8%), arrhythmia (10.8%) and sudden death (16.2%). These symptoms were precipitated by exercise in 82% of patients. One-third of the patients in whom a chest radiograph was taken had ring calcification. Angiographic findings included coronary artery occlusion (66.1%). Extensive development of collateral vessels was reported in 44.1% of patients. Autopsy findings included coronary artery aneurysms (100%) and coronary artery occlusion (72.2%). The acute vasculitis of Kawasaki disease can result in coronary artery damage and rheologic changes predisposing to thrombus formation or progressive atherosclerotic changes that may remain clinically silent for many years. Coronary artery aneurysms and calcification on chest radiography were unusual features in this group of patients. A history of antecedent Kawasaki disease should be sought in all young adults who present with acute myocardial infarction or sudden death.
The long-term consequences of the cardiovascular sequelae in Kawasaki disease remain uncertain.
We identified 594 consecutive children with acute Kawasaki disease between 1973 and 1983, and this cohort was followed up for 10 to 21 years (mean, 13.6 years). In all patients, we evaluated coronary lesions by coronary angiography just after the acute stage. One hundred and forty-six patients (24.6%) were diagnosed as having coronary aneurysms. A second angiogram was performed 1 to 2 years later in all 146 patients who previously had coronary aneurysms, which demonstrated that 72 (49.3%) of these 146 had regression in the coronary aneurysm. A third angiogram was performed for 62 patients, a fourth for 29, and a fifth for 17. By 10 to 21 years after the onset of the illness, stenosis in the coronary aneurysm had developed in 28 patients. Myocardial infarction occurred in 11 patients, 5 of whom died. In the 26 patients with giant coronary aneurysms, stenotic lesions developed in 12, and no regression occurred. The 448 patients with normal findings at the first angiogram subsequently never developed any abnormal cardiac findings. Systemic artery aneurysms developed in 13 patients (2.2%), and valvular heart disease appeared in 7 (1.2%).
The incidence of coronary aneurysm in acute Kawasaki disease was 25%, 55% of which showed regression. During follow-up, ischemic heart disease developed in 4.7% and myocardial infarction in 1.9%. Death occurred in 0.8%.
We describe a bacillus Calmette-Guérin (BCG) granuloma that occurred during the course of Kawasaki disease. A 12-month-old male infant with Kawasaki disease had an erythematous indurated plaque with prominent necrotic ulceration at the BCG vaccination site on the left upper arm. Histologic study showed a granulomatous reaction consisting of epithelioid histiocytes, lymphoid cells, and Langhans-type giant cells. No evidence of mycobacterial infection was obtained. The lesion healed completely within 2 weeks without administration of antituberculous agents. We believe that the granulomatous reaction occurred as a result of hypersensitivity to proteins in the BCG vaccine, which appeared after the onset of Kawasaki disease.
To construct a predictive instrument for developing coronary artery abnormalities in patients with acute Kawasaki disease treated with aspirin and intravenous gamma globulin within the first 10 days of illness, data available from a multicenter database of patients with acute Kawasaki disease were analyzed. A development data set (n = 212) was used to construct a sequential risk classification instrument based on easily measured baseline laboratory test results and temperature. The instrument was then validated in 3 test data sets (n = 192, 264, and 92, respectively). Risk factors used in the sequential classification instrument included baseline neutrophil and band counts, hemoglobin concentration, platelet count, and temperature on the day after infusion of intravenous gamma globulin. In the development data set, the instrument classified 123 of 212 patients (58%) as low risk; none developed coronary artery abnormalities. Among 89 patients classified as high risk, 3 of 36 female (8.3%) and 9 of 53 male patients (17.0%) developed coronary artery abnormalities. The instrument performed similarly in the 3 test data sets; no patient in any data set classified as low risk developed coronary artery abnormalities. This simple instrument allows the clinician to identify within 1 day of treatment low-risk children in whom extensive and frequent cardiac testing may be unnecessary, as well as high-risk children who require closer monitoring and may be candidates for additional therapies.
The objective of the study is to describe recent epidemiologic patterns of Kawasaki disease based on information included in patient records that had been obtained through a nationwide hospital survey in Japan.
A questionnaire and diagnostic criteria for Kawasaki disease that had been approved by the Kawasaki Disease Research Committee were sent to all pediatric departments of hospitals (2638 hospitals) with a bed capacity of at least 100. The subjects all were new patients who were treated during a 2-year period from 1995 to 1996.
A total of 12 531 children contracted the disease during the observation period. The incidence was 102.6 for 1995 and 108.0 for 1996 per 100 000 children younger than age 5 years. The male:female ratio was 1.37. The age distribution pattern showed a peak near 6 months of age. Geographic variations in the incidence suggested the existence of local outbreaks. Cardiac sequelae were seen in 12% of the patients.
More than 6000 patients suffered from Kawasaki disease each year, and its annual incidence is increasing steadily. The probable existence of local outbreaks is worthy of note. Other epidemiologic patterns were unchanged from previous years.
Features of 28 patients older than 8 years of age with acute Kawasaki disease were reviewed. Observations included a predominance of male patients and white patients, delays in diagnosis of acute Kawasaki disease, presence of additional signs and symptoms, and a substantial incidence of coronary artery abnormalities (21%) including mild transient changes.
We evaluated the efficacy of intravenous gamma-globulin (IVGG) administration for children with Kawasaki disease to establish whether additional, more advanced therapy is needed in intractable cases.
A total of 193 children with Kawasaki disease were studied retrospectively. Patients were admitted 3 to 7 days after the onset of the disease, and IVGG was administered. Laboratory measurements including white blood cell (WBC), neutrophil, and platelet counts and C-reactive protein (CRP) and albumin concentrations were determined before and 2 to 3 days after IVGG treatment. The progression of coronary artery lesions (CALs) was monitored by serial echocardiography until 30 days after treatment.
Of 193 children, 24 (12.2 %) had CALs including transient dilatation. In contrast to the other measurements, the WBC count increased in 21 of 24 (87.5%) children with CALs after IVGG therapy. The patients with increased neutrophil count and CRP concentration after IVGG therapy also had CAL formation at a high rate (78.3% and 66.7%, respectively). Among children with normal coronary arteries, elevations of the WBC and neutrophil counts and CRP concentration were observed after IVGG therapy in only 3, 6, and 8 patients, respectively (specificity: 98.2%, 97.0%, and 95.3%, respectively). Furthermore, multiple logistic regression indicated that these variables were useful predictors of CALs in KD.
Though the introduction of IVGG therapy has improved the prognosis of Kawasaki disease, approximately 10% of patients still develop CALs. The need for more aggressive therapy in IVGG-resistant cases can be recognized early by increases in the WBC and neutrophil counts and serum CRP concentration after IVGG administration.
The concept of self-management of oral anticoagulation has been shown to entail better quality of treatment than conventional management when assessed in selected adults. We have extended the concept of self-management to include children with congenital cardiac disease, hypothesizing self-management of oral anticoagulation is also possible in this subset of patients. Our aim was to assess the quality of self-management.
We trained 14 children aged from 2.2 to 15.6 years, with a mean age of 9.7 years, and their parents, in domiciliary analysis of the International Normalized Ratio and necessary adjustment of dosage of coumarin. The curriculum for training lasted for 27 weeks, and the patients and their parents were followed for a period of up to 31 months by weekly measurement of the values obtained for the International Normalized Ratio.
The patients were observed over a mean of 547 days, with a range from 214 to 953 days. The patients were within the therapeutic targetted range of the International Normalized Ratio for a median of 65.5% of the time, with a range from 17.6% to 90.4%. None of the patients experienced thromboembolic or bleeding complications requiring doctoral intervention. All the patients and their parents expressed full satisfaction with the treatment.
Self-management of oral anticoagulation provides a good quality of treatment, which is feasible and safe in selected children with congenital cardiac disease.
To assess the prevalence of superantigen secreting bacteria in children with acute Kawasaki disease (KD) relative to control patients.
Bacterial cultures were obtained in a blinded fashion from the throat, rectum, and groin of 45 patients with untreated acute KD and 37 febrile control patients from 6 centers in the United States. Cultures were processed for the presence of superantigen-producing bacteria at a central laboratory.
Staphylococci or streptococci that produced superantigens (TSST-1, SEB, SEC, SPEB, SPEC) were isolated from 25 of 45 patients with KD (56%) as compared with 13 of 37 (35%) control patients (P =.078). Because SEB- and SEC-producing Staphylococcus aureus have not been associated with KD and because they do not induce a Vbeta2+ T-lymphocyte response, we analyzed the difference between groups relative to superantigens TSST-1 or SPEB/SPEC production. TSST-1 secreting S aureus or SPEB/SPEC producing group A streptococci were isolated from 20 of 45 (44%) patients with KD compared with 7 of 37 (19%) control patients (P =.019).
The overall isolation rates of superantigen (TSST-1, SPEB, SPEC, SEB, SEC) producing bacteria between patients with KD and febrile control patients were not statistically significant. However, future studies should further examine the potential role of Vbeta2-stimulatory superantigens (TSST-1 and SPEB/SPEC) in KD.