Suppressive influence of seasonal influenza epidemic on Kawasaki disease onset.

  Kawasaki disease (KD) is an acute systemic vasculitis presenting as an infantile febrile disease. In Japan, the widespread cedar plantation commenced in 1945 has been correlated with the increased incidences of both KD and allergic rhinitis (pollinosis) since the early 1960s. We previously showed that KD was a pollen-induced, delayed-type hypersensitivity that displays biphasic peaks in both summer and winter. KD incidences decrease suddenly around February, particularly after influenza epidemics. Here we investigated the reason for a drastic decrease in KD onsets directly before spring pollen release following rapid increase after autumn pollen release leading to the biphasic pattern. We separately analyzed weekly incidences of KD and influenza in Tokyo (1987-2010) and Kanagawa (1991-2002). Repeated measures for the analysis of variance followed by Bonferroni's multiple comparison tests were performed to compare KD incidence over 3 consecutive weeks, including the weeks when the mean KD prevalence showed the steepest decrease. Next, the week with peak influenza incidence was reset for each year. KD incidence over 3 consecutive weeks, including the new origin week (adjusted week 0), was similarly analyzed. In Tokyo and Kanagawa, KD incidence significantly decreased only after resetting the influenza peak time. These findings suggested that influenza epidemics suppressed KD onset.

Enfermedad de Kawasaki / Malaltia de Kawasaki / Kawasaki´s disease

La malaltia de Kawasaki (MK) és una vasculitis sistèmica aguda d'etiologia desconeguda. El diagnòstic es basa en criteris clínics que inclouen febre, exantema, conjuntivitis, canvis en les extremitats, eritema de la mucosa oral i llavis, i adenopaties cervicals. No obstant això, aquests criteris tenen una sensibilitat i una especificitat baixes i, per tant, altres característiques clíniques i de laboratori poden ser útils per establir el diagnòstic, sobretot en els casos d'MK atípica o incompleta. El pronòstic depèn de l'extensió de l'afectació cardíaca; els aneurismes coronaris, que es de-sen volupen en el 20-25% dels pacients no tractats, poden provocar infart de miocardi o mort sobtada en l'edat adulta. El tractament amb altes dosis d'immunoglobulina intrave-nosa és eficaç per reduir el risc d'aneurismes coronaris en la majoria dels casos i és el tractament d'elecció. En aquesta revisió analitzem la clínica, l'epidemiologia i el tractament d'aquesta malaltia típica de l'edat pediàtrica

La enfermedad de Kawasaki (EK) es una vasculitis sistémica aguda de etiología desconocida. El diagnóstico se basa en criterios clínicos que incluyen fiebre, exantema, conjuntivitis, cambios en las extremidades, eritema de la mucosa oral y labios, y adenopatías cervicales. Sin embargo, estos criterios tienen una sensibilidad y una especificidad bajas y, por tanto, otras características clínicas y de laboratorio pueden ser útiles para establecer el diagnóstico, sobre todo en los casos de MK atípica o incompleta. El pronóstico depende de la extensión de la afectación cardiaca; los aneurismas coronarios, que se desarrollan en el 20-25% de los pacientes no tratados, pueden provocar infarto de miocardio o muerte súbita en la edad adulta. El tratamiento con altas dosis de inmunoglobulina intravenosa es eficaz para reducir el riesgo de aneurismas coronarios en la mayoría de los casos y es el tratamiento de elección. En esta revisión analizamos la clínica, la epidemiología y el tratamiento de esta enfermedad típica de la edad pediátrica (AU)

Kawasaki disease (MK) is an acute systemic vasculitis of unknown etiology. The diagnosis is based on clinical criteria that includes fever, rash, conjunctivitis, changes in the limbs, erythema of the oral mucosa and lips, and cervical lymphadenopathy. However, these criteria have a low sensitivity and specificity and, therefore, other clinical and laboratory features may be helpful in establishing the diagnosis, especially in cases of atypical or incomplete MK. The prognosis depends on the extent of heart involvement; coronary aneurysms, which develop in 20-25% of untreated patients can cause a heart attack or sudden death in adulthood. Treatment with high doses of intravenous immunoglobulin is effective to reduce the risk of coronary aneurysms in most cases and is the treatment of choice. In this review we analyze the symptoms, epidemiology and treatment of this disease, typical of paediatric patients (AU)

Kawasaki disease: an evolving paradigm.

Kawasaki disease (KD) is a self-limited childhood systemic vasculitis that exhibits a specific predilection for the coronary arteries. KD predominantly affects young children between the ages of 6months and 4years. Incidence rates in Asians are up to 20 times higher than Caucasians. The aetiology of KD is not known. One reasonable open hypothesis is that KD is caused by an infectious agent that produces an autoimmune disease only in genetically predisposed individuals. The typical presentation of KD is a young child who has exhibited a high swinging fever for five or more days that persists despite antibiotic and/or antipyretic treatment. The lips are dry and cracked. There is a characteristic strawberry tongue, and a diffuse erythema of oropharyngeal mucosal surfaces. Lymphadenopathy is usually unilateral and confined to the anterior cervical triangle. Coronary aneurysms generally appear during the convalescence phase (beginning during the second week). The absence of any laboratory tests for KD means that the diagnosis is made by the presence of a constellation of clinical features. The aim of echocardiography is to assess the presence of coronary artery dilatation or aneurysm formation. Effective therapies exist for most patients with acute KD, but the exact mechanisms of action are not clear. Treatment with aspirin and intravenous immunoglobulins (IVIG) are first-line therapies. However, options are plentiful for the children who fail this treatment, but these treatments are not as beneficial. Some centres attempt to salvage resistant patients using intravenous pulsed doses of methylprednisolone. Other centres use infliximab or combinations of these approaches.

A combination of cross correlation and trend analyses reveals that Kawasaki disease is a pollen-induced delayed-type hyper-sensitivity disease.

Based on ecological analyses we proposed in 2003 the relation of Kawasaki Disease (KD) onset causing acute febrile systemic vasculitis, and pollen exposure. This study was aimed at investigating the correlation between pollen release and the change in the numbers of KD patients from 1991 to 2002 in Kanagawa, Japan. Short-term changes in the number of KD patients and medium- to long-term trends were analyzed separately. Short-term changes in the number of KD patients showed a significant positive cross correlation (CC) with 9- to 10-month delay following pollen releases, and a smaller but significant CC with 3- to 4-month delay. Further, a temporal relationship revealed by positive CC distribution showed that pollen release preceded KD development, suggesting that pollen release leads to KD development. A trend in patient numbers was fitted by an exponential curve with the time constant of 0.005494. We hypothesized that the trend was caused by the cumulative effects of pollen exposure for elapsed months on patients who may develop KD. By comparing the time constants of fitted exponential curve for each pollen accumulation period with 0.005494, the exposure period was estimated to be 21.4 months, which explains why approximately 50% of patients developed KD within 24 months from birth.

Administration of human immunoglobulin suppresses development of murine systemic vasculitis induced with Candida albicans water-soluble fraction: an animal model of Kawasaki disease.

We investigated the inhibitory effect of human immunoglobulin (h-Ig) on the development of coronary arteritis in a murine model of vasculitis induced with a Candida albicans water-soluble fraction (CAWS). CAWS was intraperitoneally injected to C57BL/6 mice for 5 days. Then h-Ig was administered according to various schedules. The animals were sacrificed in week 5, and the status of vasculitis in the coronary arteries and the aortic root was investigated histologically. The groups in which h-Ig was administered for 5 days from day 3 and from day 5 of the experiment showed a significant reduction in the incidence of panvasculitis. In addition, the scope and severity of the inflammation of the aortic root and the coronary arteries were reduced in both groups. In the group administered h-Ig for 5 days from day 1 and the group administered a high dose of h-Ig once on day 1 or day 3, no suppression of development of vasculitis was observed. The h-Ig acted by suppressing the generation and progression of vasculitis in this CAWS-induced murine vasculitis model.

Leukotriene B4 and Kawasaki disease.

The role of LTB4 in Kawasaki disease as a chemo-attractant and immunomodulator is reviewed through our own experience and reports by other investigators. In our experiment using 19 patients, we measured calcium ionophore-stimulated LTB4 synthesis in PMNs obtained in three different stages of the illness (acute, convalescent and recovered phases). LTB4 synthesis was significantly increased in the convalescent phase of the illness. Other investigators showed increased serum-LTB4 concentration in acute as well as convalescent phases, suggesting that LTB4 participated in the inflammatory process of Kawasaki disease as an inflammatory mediator and immunomodulator. However, no difference was found in LTB4 synthetic activity in PMNs in any phases of the illness between the patients with and without coronary lesions, which indicated that LTB4 was not a parameter of coronary aneurysm formation. Therapeutic use of high-dose gamma-globulin showed a tendency to decreased LTB4 synthesis in PMNs, although it is not conclusive.