Febrile Mucocutaneous Lymph Node Syndrome Research Articles

Kawasaki Disease: Pathology, Risks, and Management.

Kawasaki disease (KD), first reported as an acute febrile mucocutaneous lymph node syndrome, is a self-limiting vasculitis of unknown etiology. The most important aspect of KD is the prevention of coronary artery lesion (CAL) because myocardial ischemia or infarction due to CAL might be lethal. In addition to the CAL, patients with KD develop systemic vasculitis, which indicates the presence of vascular endothelial damage. Studies assessing pulse wave velocity or percentage change in flow-mediated dilatation have shown that aortic stiffness is increased in patients with KD history. In contrast, the cardio-ankle vascular index, a novel parameter not affected by blood pressure, has not demonstrated increased aortic stiffness in patients with KD. Although many studies using various parameters have suggested a risk of atherosclerosis in patients with a history of KD, a few others have reported no significant differences between KD patients and controls. Therefore, it will be necessary to thoroughly understand the characteristics of each parameter, before evaluating the results of those studies, to understand systemic vascular dysfunction in these populations, and to manage their vascular health. Although it is controversial whether the risk of atherosclerosis in patients with KD is higher, those with CAL are thought to be at a high risk of atherosclerosis. Therefore, appropriate treatment to prevent CAL in the acute phase and subsequent regular follow-up is important. Here, we review the pathology, risk, and management of vascular disorders, especially systemic vascular disorders, in patients with KD history.

History of Kawasaki disease

We describe a short history of Kawasaki disease. In 1967, we published a paper entitled 'Infantile acute febrile mucocutaneous lymph node syndrome with specific desquamation of the fingers and toes. Clinical observation of 50 cases'; this was the first report on what is now called Kawasaki disease. Since then, many reports on cardiology, treatment, epidemiology, pathology and etiology of Kawasaki disease have been published. Furthermore, a recent Chapel Hill Consensus Statement on Kawasaki disease in the classification of vasculitis is given, along with a figure on the relationship and classification of childhood vasculitis by autopsy material.

Head and neck manifestations of Kawasaki disease

Kawasaki disease, also known as acute infantile febrile mucocutaneous lymph node syndrome, is a self-limited vasculitic disease of infants and young children. The cause of the disease remains uncertain. Within the constellation of signs and symptoms, there are numerous otolaryngologic manifestations. The following represents the largest series of patients in the otolaryngology literature, involving 155 confirmed cases of Kawasaki disease as treated at our institution during the last 10 years. The demographic data, clinical pictures of the typical and atypical forms of the illness, as well as the laboratory values, therapy and complications are discussed.

Ultrastructural Characteristics of Myocardial and Coronary Microvascular Lesions in Kawasaki Disease

Kawasaki disease (KD) is an acute febrile mucocutaneous lymph node syndrome with multisystemic vasculitis affecting mainly infants and children. Although several studies on cardiovascular lesions in KD have been done at the light microscopic level, the ultrastructural characteristics and incidences of these lesions have not been well defined. In order to investigate the myocardial and coronary microvascular sequelae in KD, we performed an ultrastructural study on endomyocardial biopsy specimens obtained during follow-up from 54 patients who had typical clinical manifestations of KD, of whom 47 had associated coronary aneurysms as demonstrated by coronary arteriography (CAG) or two-dimensional echocardiography in the acute or healed stage. The average age of onset was 2.2 years old and the duration of illness was from 2 months to 23 years. Follow-up CAG showed that the coronary aneurysms persisted in 33 of the 47 patients (8 with associated stenosis) and resolved in the remaining 14 patients. Ultrastructurally, the myocardial changes revealed hypertrophy, various degrees of degeneration, proliferation and abnormality of mitochondria, infiltration of a small number of lymphocytes, and fibrosis. The coronary microvascular lesion was characterized by microvascular dilatation, endothelial cell injury, platelet aggregation with thrombosis, and stenotic lumen with thickened walls in the small arterioles. It persisted after convalescent stage even up to 23 years and closely correlated with the myocardial sequelae. Moreover, significantly increased incidences of myocardial and coronary microvascular lesions were found in patients with coronary artery lesion. These findings suggest the coronary microvascular lesion as a possible underlying factor of persistent sequelae in KD.

Kawasaki Disease With Particular Emphasis on Arterial Lesions

Kawasaki disease (KD, or acute febrile mucocutaneous lymph node syndrome (MCLS)) was first described as a clinical entity in 1967 by Dr. Tomisaku Kawasaki of the Japan Red Cross Medical Center. Originally, it was thought to have a favorable prognosis, but as epidemiological surveys, augmented by pathological studies, have shown, it has come to be recognized as an often fatal disorder. In this report, the clinical symptoms, historical background, present status of research and epidemiological problems of KD are first described, and then we present a pathological and morphological outline of KD, focusing on pathological changes in the blood vessels, and the relationships of these changes to 1) the morphogenesis of arteritis, 2) the mechanism of coronary artery aneurysm formation and its sequelae, and 3) juvenile arteriosclerosis.

Pathological observations concerning the cardiovascular lesions in Kawasaki disease

In about 1967, a new clinical entity in infants and children was described in Japan. It was an acute febrile illness associated with engorgement of the conjunctivas, labial erythema, and swelling of the deep cervical lymph nodes without suppuration. This disease is usually called the acute febrile mucocutaneous lymph node syndrome or, more simply, Kawasaki disease.

KAWASAKI SYNDROME

Kawasaki syndrome is an acute multisystem inflammatory disease of young children first described by Tomasaku Kawasaki in the Japanese literature in 1967. He reported 50 cases of this entity under the rubric of acute febrile mucocutaneous lymph node syndrome, a designation that has more recently been superseded by the eponym Kawasaki syndrome. The disorder was further delineated and brought to the attention of American pediatricians in 1974. Recognition of the syndrome followed rapidly, and Melish, Hicks and Larson published the first series of American cases from Hawaii in 1976. Subsequently, Kawasaki syndrome has been documented worldwide. Although the disorder is known to be a systemic vasculitis with predilection for the coronary arteries, the etiology has remained obscure despite intense investigative efforts.

Kawasaki Disease and an Unusual Primary Infection with Epstein-Barr Virus

To the Editor.— Kawasaki disease (acute febrile mucocutaneous lymph node syndrome, MCLS)1 has been increasingly encountered throughout Japan. Furthermore, this syndrome has also been identified in other countries.2 We previously suggested that this particular disease may be closely associated with an abnormal immune response to Epstein-Barr virus (EBV).3 To obtain more information, further investigations were carried out on another group of 45 Japanese patients (27 boys and 18 girls; mean age of 2.3 years) that satisfied the criteria for a definite diagnosis of MCLS.3

Tubuloreticular structures and parallel tubular arrays in the lymphocytes of children with aplastic anemia and acute febrile mucocutaneous lymph node syndrome: Electron microscopic observations

AbstractTubuloreticular structure was found in 3 and 30% of the lymphoid cells from two consecutive cases of MCLS and in 10 and 15% of the lymphoid cells from two consecutive cases of aplastic anemia. Parallel tubular array was found in 8 and 24% of the lymphoid cells from the cases of MCLS and in 3% of the lymphoid cells from the cases of aplastic anemia. The possibility of the viral etiology of the both diseases was discussed.eases was discussed.

Kawasaki syndrome--a new disease?

Kawasaki recognized in 1967 the acute febrile mucocutaneous lymph node syndrome (MCLS) as a well defined entity among a variety of hitherto unidentified atypical exanthems. The etiology is uncertain. There are close relations to infantile polyarteritis nodosa (IPN) which is probably the severe variant of Kawasaki's disease. Histologically it is a generalized necrotizing vasculitis, most probably caused by circulating immune complexes. The disease is supposed to be initiated by various infections in patients with certain predispositions. Considerations about etiology and pathogenesis as well as relations to IPN are mainly discussed theoretically. Therefore it is recommended to investigate the Kawasaki syndrome following a devised protocol.

Studies on Aspirin Administration in Acute Febrile Mucocutaneous Lymph Node Syndrome (MCLS), Based on the Antithrombotic Effects of Aspirin

Studies on Aspirin Administration in Acute Febrile Mucocutaneous Lymph Node Syndrome (MCLS), Based on the Antithrombotic Effects of Aspirin

The Hematological Studies on Acute Febrile Mucocutaneous Lymph Node Syndrome (MCLS) with Special Reference of the Platelets—The Thrombus Formation and Etiology in MCLS—

The Hematological Studies on Acute Febrile Mucocutaneous Lymph Node Syndrome (MCLS) with Special Reference of the Platelets—The Thrombus Formation and Etiology in MCLS—

Left ventricular function in patients with coronary arteritis due to acute febrile mucocutaneous lymph node syndrome or related diseases

Reports of a mucocutaneous lymph node syndrome that frequently affects the coronary arteries have been increasing in Japan and other countries including the United States. Twelve patients with a documented history of mucocutaneous lymph node syndrome or a related coronary arteritis were studied with right and left heart catheterization, cardiac output measurements, left cineventriculography and selective coronary arteriography. These patients were separated into two groups on the basis of coronary arteriographic findings. Group 1 comprised six patients with normal coronary arteriograms; group 2 included the remaining six patients with coronary arterial aneurysm or occlusion. Left ventricular function differed in the two groups. It remained essentially normal in group 1 whereas decreased ejection fraction, increased end-diastolic volume, elevated end-diastolic pressure or mitral regurgitation were evident in four of the six patients in group 2. Two ventriculographic abnormalities were identified: (1) regional contraction abnormality secondary to myocardial infarction, and (2) generalized hypokinesia without electrocardiographic evidence of infarction, probably caused by myocarditis resulting from arteritis. Two patients with severe coronary arterial obstruction and myocardial infarction underwent successful aortocoronary bypass grafting. Postoperatively both had patency of all grafts and one had improved left ventricular function. These experiences have first shown the feasibility and significance of surgical management for selected patients with coronary arterial lesions due to coronary arteritis caused by the mucocutaneous lymph node syndrome or related diseases.

Cardiac death in mucocutaneous lymph node syndrome

A 12 year old boy had 4 symptom-free years after hospitalization for acute febrile mucocutaneous lymph node syndrome before he died suddenly from extensive myocardial infarction. Current evidence suggests that many patients with this syndrome have coronary artery disease and that those with significant cardiac findings should be studied with coronary angiography. Serial studies are recommended because of the danger of sudden death.

Ultrastructure of the myocardium in acute febrile mucocutaneous lymph node syndrome.

A fine structure of the myocardium was examined in the acute febrile mucocutaneous lymph node syndrome, which was recently prevailing in Japan. The right ventricular myocardial cells in ten cases were observed through endomyocardial biopsies. On light microscopy, accumulation of histiocytes was demonstrated in some cases. Electron microscopic examinations revealed myofibrillar changes, increased glycogen contents and other degenerative changes. On the myocardium of a case in which a biopsy was performed during the active phase of the disease, these changes were prominent. However, these changes were also observed for some months to some degree.

Elevated levels of immunoglobulin E in the acute febrile mucocutaneous lymph node syndrome.

Mucocutaneous lymph node syndrome (MCLS) is a newly recognized disease characterized by fever persisting for more than 5 days, an erythematous skin eruption, conjunctival congestion, dry red fissured lips, reddened tongue, palms, and soles, nonpurulent lymphadenopathy, and sometines diarrhea, arthralgia, and aseptic meningitis. Additional features may include carditis, pericarditis, aneurysmal dilation and thrombosis of coronary arteries, and sudden death. There is a striking similarity of fatal cases to infantile polyarteritis nodosa, a disease recently reported to be associated with elevated levels of serium IgE. Indeed, it is likely that MCLS represents a disease which can progress to polyarteritis nodosa in infants and young children. The paired acute and convalescent serum IgE levels of 20 subjects with acute nonfatal MCLS were studied along with 20 near-age unaffected controls from the same communities in Japan. The results indicate that most if not all subjects with MCLS in the study had an elevation of total serum IgE during the acute phase of the disease (geometric mean 157 IU/ml compared with the control value of 38 IU/ml, P = 0.005). The level appeared to reach a peak 1-2 weeks after onset and declined over the ensuing 1-2 months.

Previously Reported Unrecognized MLNS

In the September 1974 issue of Pediatrics, Kawasaki et al.1 described the clinical manifestations of acute febrile mucocutaneous lymph node syndrome (MLNS), and Yanagisawa et al.2 described a patient with MLNS who died of aneurysmal dilatation and bilateral obstruction of the coronary arteries. In an editorial in the same issue, Fetterman and Hashida3 suggested that the syndrome had not been recognized in the continental United States. Such a case may have been described but not recognized as a case of MLNS.

Cardiac Involvement and Prognosis in Acute Mucocutaneous Lymph Node Syndrome

Cardiac involvement and prognosis were studied in the acute febrile mucocutaneous lymph node syndrome which recently has been found among Japanese infants and younger children. The reason for its particular predilection for the main coronary arteries and the pathologic process are discussed in relation to the pathogenesis and nutrient of the main coronary arteries.

Coronary aneurysms in infants and young children with acute febrile mucocutaneous lymph node syndrome

In 1967, Kawasaki, in Japan, first described a new syndrome affecting infants and young children-an acute, febrile illness with mucocutaneous involvement associated with swelling of cervical lymph nodes. The prognosis is usually good but recently it has become evident that 1-2 percent of the patients die suddenly from acute heart failure. Infantile polyarteritis (nodosa-like arteritis) accompained by coronary aneurysm and thrombosis has been noted in postmortem examinations. Twenty patients surviving the illness were examined by coronary angiography; 12 of the 20 had abnormal coronary angiograms; seven patients had coronary aneurysms. Complete regression of the coronary aneurysms was proved in two patients at subsequent angiography. One patient developed mitral regurgitation as a result of papillary muscle dysfunction. One had a coronary aneurysm without symptoms two years after the onset of illness.

Myocardial Infarction Due to Coronary Thromboarteritis, Following Acute Febrile Mucocutaneous Lymph Node Syndrome (MLNS) in an Infant

A previously healthy 6-month-old male infant was admitted to our clinic for persistent high fever and an erythematous skin rash. Hyperemia of conjunctivae, redness of oral mucosa, and swelling of several cervical lymph nodes were also observed. Soon after admission he developed jaundice which continued for one week. Results of laboratory examinations revealed leukocytosis, elevated ESR, mild proteinuria, leukocytes in urinary sediment, hyperbilirubinemia, increased serum alpha-2-globulin and positive CRP. Serum ASO titer was less than 100 Todd units and complement fixation reactions for various viruses were not significant. Cultures of blood, urine, stool and throat were negative. He was treated with antibiotics and steroids and improved gradually, but then developed signs and symptoms of congestive heart failure. An ECG showed a pattern of extensive myocardial infarction. He died of congestive heart failure at the age of 21 months. Autopsy findings revealed focal aneurysmal dilatation and obstruction of the bilateral coronary arteries. The myocardial infarction involved the septum of the anterolateral wall of the left ventricle. The coronary arteries, distal aorta, iliac arteries and pulmonary arteries were also involved, but very slightly. The symptoms, laboratory findings and the course of this patient were compatible with those of acute febrile mucocutaneous lymph node syndrome (MLNS), MLNS has been accepted as a new syndrome by most Japanese pediatricians in recent years. Its etiology is still unknown. Some of the patients with this syndrome had died suddenly of coronary thromboarteritis after recovering from the acute illness. Although autopsy findings of the fatal cases have been similar to those describing infantile polyarteritis nodosa, the relationship between MLNS and infantile polyarteritis is controversial.