Yuki Yokouchi

Neutrophilic involvement in the damage to coronary arteries in acute stage of Kawasaki disease

Abstract  Background : There has been no morphological evidence that polymorphonuclear leukocytes (PMNL) infiltrate the coronary arterial lesions of acute Kawasaki disease (KD) patients, although clinical data indicate the activation of PMNL.

Histopathological features of murine systemic vasculitis caused by Candida albicans extract--an animal model of Kawasaki disease.

AbstractObjective and Design: We examined the histopathological features of systemic vasculitis caused in mice by injection of a Candida albicans (C. albicans) extract and investigated the principal genetic roles in the development of vasculitis. Materials and Methods: C. albicans extract was injected intraperitoneally for five consecutive days in the 1st and 5th weeks to CD-1, C57BL/6N, C3H/HeN, BALB/cAnN, DBA/2N and CBA/JN mice. At week 8, mice were killed, and histological examination was performed by light microscopy. Results: Arteritis had developed in 66% of CD-1 mice. The extramural coronary arteries and aortic root close to the orifice of coronary arteries were most frequently involved. Histologically, the characteristic feature of the arteritis was proliferative and granulomatous inflammation accompanied by numerous macrophages, lymphocytes, plasma cells and neutrophils. Fibrocellular intimal thickening with destruction of the internal elastic lamina and media was also observed. Five mouse strains after injection of C. albicans extract were clearly classified into a resistant group (CBA/JN, DBA/2N and BALB/cAnN mice) and a sensitive group (C3H/HeN and C57BL/6N mice). The inbred mouse strains which showed the same histocompatibility-2 (H-2) haplotype exhibited a different susceptibility to development of vasculitis. Conclusion: This arteritis murine model shows unique histological features that have not been observed in other animal vasculitis models and it most closely resembles Kawasaki disease in humans. The genetic control of susceptibility to induction of vasculitis by the C. albicans extract is dependent to the mouse strains, but is not linked to the H-2 loci.

Pathogenesis of Kawasaki disease

Kawasaki disease (KD) most frequently affects infants and young children under 5 years of age. This disease is considered a kind of systemic vasculitis syndrome, and primarily invades the medium‐sized muscular arteries, including coronary arteries. Diagnosis of KD is based on characteristic clinical signs and symptoms, which are classified as principal clinical findings and other clinical and laboratory findings. Even though the aetiology of KD is unknown, epidemiological data suggest that some kinds of infectious agents are involved in the onset of KD. In addition, the data indicate that host genetics underlie the diseases pathogenesis. Histologically, coronary arteritis begins 6–8 days after the onset of KD, and leads immediately to inflammation of all layers of the artery. The inflammation spreads completely around the artery; as a result, structural components of the artery undergo intense damage; the artery then begins to dilate. Inflammatory cell infiltration continues until about the 25th day of the disease, after which the inflammatory cells gradually decrease in number. KD arteritis is characterized by granulomatous inflammation that consists of severe accumulation of monocytes/macrophages. Aberrant activation of monocytes/macrophages is thought to be involved in the formation of vascular lesions. The lesions in all the arteries are relatively synchronous as they evolve from acute to chronic injury. There is no fibrinoid necrosis nor any mixture of acute inflammatory lesions and scarring lesions, which are characteristics in polyarteritis nodosa in KD.

Histopathological characteristics of myocarditis in acute-phase Kawasaki disease

Harada M, Yokouchi Y, Oharaseki T, Matsui K, Tobayama H, Tanaka N, Akimoto K, Takahashi K, Kishiro M, Shimizu T & Takahashi K 
(2012) Histopathology
Histopathological characteristics of myocarditis in acute‐phase Kawasaki disease

Update on etio and immunopathogenesis of Kawasaki disease.

Purpose of reviewThis review first discusses the pathogenesis of Kawasaki disease based on the results of recently performed studies aimed at identifying Kawasaki disease-susceptibility genes and the results of analyses of the immune system. Following that, we discuss the findings generated using a murine Kawasaki disease arteritis model and speculate regarding the mechanism of Kawasaki disease onset based on immune function aberrations seen in that model. Recent findingsRecent advances in gene analysis studies of Kawasaki disease are contributing not only to prediction of disease susceptibility but also to improving our understanding of the pathogenesis of Kawasaki disease and development of new improved therapies. In addition, Th17/Treg imbalance is observed in patients with acute-phase Kawasaki disease. Th17/Treg imbalance may be an important factor causing disturbed immunological function. IL-17 induced by Th17 cells have proinflammatory properties and act on inflammatory cells, thereby inducing expression of cytokines and chemokines and resulting in tissue inflammation. SummaryKawasaki disease vasculitis may be triggered by aberrant activation of inflammatory cytokines mediated by IL-17 that is produced by Th17 cells that have been activated by some infectious agent(s).

Allergic fungal sinusitis caused by Bipolaris spicifera and Schizophyllum commune

There have been very few reports in Japan of patients with allergic fungal sinusitis (AFS). We describe two cases caused by Bipolaris spicifera and Schizophyllum commune. The patients were a 70-year-old male (Case 1) and a 55-year-old female (Case 2). Both presented with nasal obstruction and purulent nasal discharge. CT scans revealed each to have a soft tissue mass extending from the ethmoid sinus to the sphenoid sinus. In addition, pathological studies on the contents of the paranasal sinuses of both patients revealed the presence of fungal elements in the allergic mucin. Microbiological studies resulted in the recovery of Bipolaris spicifera from Case 1 and Schizophyllum commune from Case 2. To date there have been no reports of AFS due to these two fungi in Japan. It is very important in the diagnosis of AFS to demonstrate the presence of fungal elements in the allergic mucin. Squash cytology of the paranasal sinus contents was especially useful for proving the presence of fungi.

Kawasaki Disease as a Systemic Vasculitis in Childhood

Kawasaki disease is a disease of unknown etiology that most frequently affects infants and children under 5 years of age. Inflammation occurs in medium-sized muscular arteries throughout the body including the coronary artery, being classified as a systemic vasculitis syndrome. Histopathological investigations of Kawasaki disease have mainly focused on the coronary artery because it is directly associated with the cause of death. However, to identify the cause and pathology of Kawasaki disease, it is necessary to investigate lesions of whole organs. Thus, we attempted to review lesions in organs other than the heart and hypotheses of pathogenesis recently attracting attention.

Mizoribine provides effective treatment of sequential histological change of arteritis and reduction of inflammatory cytokines and chemokines in an animal model of Kawasaki disease

The incidence of panvasculitis in the coronary arteries and aortic root was 100% in the control group. The incidence of panvasculitis in the MZR group decreased to 50%. Moreover, the scope and severity of the inflammation of those sites were significantly reduced in the MZR group as well as the IgG group. On the other hand, increased cytokines and chemokines, such as IL-1α, TNF-α, KC, MIP-1α, GM-CSF, and IL-13, in the nontreatment group were significantly suppressed by treatment with MZR, but the MCP-1 level increased. In addition, IL-1α, TNF-α, IL-10, IL-13, and MIP-1α were suppressed by treatment in the IgG group.BackgroundIntravenous immunoglobulin (IVIg) treatment results in an effective response from patients with acute-phase Kawasaki disease (KD), but 16.5% of them remain nonresponsive to IVIg. To address this therapeutic challenge, we tried a new therapeutic drug, mizoribine (MZR), in a mouse model of KD, which we have established using injections of Candida albicans water-soluble fractions (CAWS).MethodsCAWS (4 mg/mouse) were injected intraperitoneally into C57BL/6N mice for 5 consecutive days. MZR or IgG was administered for 5 days. After 4 weeks, the mice were sacrificed and autopsied, the hearts were fixed in 10% neutral formalin, and plasma was taken to measure cytokines and chemokines using the Bio-Plex system.ResultsThe incidence of panvasculitis in the coronary arteries and aortic root was 100% in the control group. The incidence of panvasculitis in the MZR group decreased to 50%. Moreover, the scope and severity of the inflammation of those sites were significantly reduced in the MZR group as well as the IgG group. On the other hand, increased cytokines and chemokines, such as IL-1α TNF-α, KC, MIP-1α, GM-CSF, and IL-13, in the nontreatment group were significantly suppressed by treatment with MZR, but the MCP-1 level increased. In addition, IL-1α, TNF-α, IL-10, IL-13, and MIP-1α were suppressed by treatment in the IgG group.ConclusionMZR treatment suppressed not only the incidence, range, and degree of vasculitis, but also inflammatory cytokines and chemokines in the plasma of the KD vasculitis model mice, suggesting that MZR may be useful for treatment of KD.

Histopathological study of lymph node lesions in the acute phase of Kawasaki disease

Aims:  To review the histopathological features of cervical LNs, and to clarify the changes in extracervical LNs, in acute Kawasaki disease (KD).

Primary cardiac synovial sarcoma: a case report and literature review.

Primary cardiac synovial sarcoma is a rare disease. A 51‐year‐old man visited our hospital with the chief complaint of palpitations and shortness of breath while exercising. Copious bloody pericardial effusion and a multicystic intrapericardial tumor were detected. A primary cardiac malignant tumor was suspected, an open‐chest tumor resection was performed with the objectives of diagnosis and treatment. Histologically, the tumor cells were uniformly spindle‐shaped with an ovoid or oval nucleus, they had proliferated in fascicular fashion. In addition myxoid degeneration, a hemangiopericytomatous vascular pattern and pseudorosette formation were seen in some areas of the tumor. Based on the histopathological and immunohistochemical findings and reverse transcription polymerase chain reaction detection of SS18‐SSX1 fusion transcripts, a monophasic fibrous type synovial sarcoma was diagnosed. Postoperative radiation therapy was administered and there had been no recurrence 9 months after the surgery.