Acute Stage Of Kawasaki Disease Research Articles

Immunohistologic demonstration of platelet-derived growth factor(PDGF) in skin biopsies from acute stage of Kawasaki disease

The involvement of endothelial cells and vascular smooth muscle cells in the initiation, formation and development of aneurysmal dilatation of coronary arteries in Kswasaki disease(KD) have been emphasized. It has been thought that specific growth factors may have an effect on anintimal thickening and vascular dysfunction. Plateletderived growth factor(PDGF) is reported to be involved in various clinical situations such as wound healing,atherogenesis,embryogenesis, and infectious diseases. In this regard, we explored the localization of PDGF in KD. Sections of skin biopsies from 8 KD patients were investigated using the mouse anti-human PDGF monoclonalantibody. Samples obtained in the acute stage were stained with ABC technique. As a result, PDGF was detected in the dermis and epidermis. The prominent staining for PDGF was found in the endothelial lining of dilated qapillaries and in the cytoplasm of macrophages~ Positive staining for PDGF was particularly associated with macrophage infiltrates. In conclus{on, it is postulated that PDGF may play an importantrole in the initiation and/or healing process of vasculitis, and skin lesion in KD. { 28

Histopathological findings of right endomyocardial biopsy specimen after γ-globulin administration in acute stage of Kawasaki disease

Background: Recent studies demonstrate that chronic anal fissure can be the consequence of a local ischemic process. Thus hypothesizing that at the perianal level the interaction of immune component with endothelium could constitute a mechanism determining ischemia and hypertonia, the presence or absence of circulating anti-endothelial cell antibodies (AECAs) was determined in the serum of patients with anal fissure. Methods: The study was carried out on 30 patients: 10 with posterior chronic anal fissure (group 1), 10 with grades III and IV hemorrhoids (group 2), and 10 without previous or active anorectal disease, or both (group 3). An indirect immunofluorescence assay on sections of rat kidney tissue was used to identify AECA in the peripheral blood. Results: The assay result was positive for AECAs in 12 patients, all with anorectal disease when compared to the control group (P = .001). The basal anal tone was higher in the AECA-positive patients than in the AECA-negative patients (P = .001). Conclusions: Only the patients with anal fissure or hemorrhoids were AECA positive. All healthy controls tested negative for AECA. Although the number of subjects studied is small, the presence of auto-antibodies directed against the endothelial cells in the serum of these patients supports the hypothesis that the endothelium is involved in the anal disease.(Surgery 1999; 126:535-40.)

Salicylate treatment in Kawasaki disease: high dose or low dose?

Salicylate is the basic therapy for Kawasaki disease, however its optimal dose is controversial. We investigated the therapeutic efficacy of high dose (100 mg/kg per day, n = 30) versus low dose (30 mg/kg per day, n = 30) salicylate. Duration of fever, SGPT, serum salicylate, plasma thromboxane B2 (TxB2) and 6-keto-prostaglandin F1 alpha (PGF1 alpha) levels were compared before enrollment and on days 4, 7 and 14 of treatment. In the high dose group, duration of fever was significantly shorter than that of the low dose group (3.2 +/- 0.3 versus 5.4 +/- 0.8 days, P less than 0.05), however, SGPT levels were significantly elevated (157 +/- 34 versus 48 +/- 11 IU/1, P less than 0.05). No differences in the incidence of coronary artery lesions were observed (5/30 versus 7/30). Plasma TxB2 production was completely blocked in both groups, and plasma 6-keto-PGF1 alpha levels in the high dose group on day 14 was lower than that in the low dose group (39 +/- 8 versus 159 +/- 65 pg/ml, P less than 0.05). SGPT and plasma 6-keto-PGF1 alpha correlated with serum salicylate concentration. These data suggest that high dose salicylate therapy may be disadvantageous as anti-thrombotic therapy, and supports the notion that low dose therapy is safe in the acute stage of Kawasaki disease.

Increased Expression of FcεR2/CD23 on Peripheral Blood B Lymphocytes and Serum IgE Levels in Kawasaki Disease

We analyzed the expression of Fc epsilon R2/CD23 on the peripheral blood B lymphocytes of 10 patients with Kawasaki disease (KD) using a fluorescence-activated cell sorter. The absolute count of CD23-positive B lymphocytes and the ratio of CD23-positive B lymphocytes to B lymphocytes were high during the acute stage of KD in comparison to those during the convalescent stage and in control subjects. In addition, both the increased number of CD23-positive B lymphocytes and the increased serum IgE levels appeared during the latter part of the acute stage. These results suggest that the increased number of CD23-positive B lymphocytes during the latter part of the acute stage in KD reflect the activation of B lymphocytes and have an important role in IgE-mediated immunity.

Expression of [formula omitted] on peripheral blood macrophages/monocytes in Kawasaki disease

We analyzed the expression of FcϵR2 CD23 on peripheral blood macrophages/monocytes in 12 patients with Kawasaki disease (KD) using a fluorescence-activated cell sorter. The absolute counts of CD14+ macrophages/monocytes and CD23+ macrophages/monocytes were high, and were positively correlated during the acute stage of KD. These results indicate that the increased number of macrophages/monocytes during acute KD have the FcϵR2 CD23 antigen present on the surface of the cells, suggesting that peripheral blood macrophages/monocytes have been activated.

Class II major histocompatibility antigen expression on coronary arterial endothelium in a patient with Kawasaki disease

To investigate the class II major histocompatibility antigen expression on coronary arterial endothelium of Kawasaki disease and immunophenotypes of the infiltrating cells in the coronary vascular lesions, myocardial sections from a patient who died during the acute stage of Kawasaki disease were studied using an immunoperoxidase technique. The mononuclear cells in the lesions mainly consisted of macrophages and T cells, whereas B cells and NK K cells were not seen. The majority of T cells reacted with Leu-3a antibodies, and only a few reacted with Leu-2a antibodies. Cells bearing the interleukin-2 receptor, indicative of activated T cells, were also found in the lesions. To determine the distribution of class II antigen, we used anti-HLA-DR antibodies. The massive expression of HLA-DR antigen on mononuclear cells was found in the lesions. In addition, the HLA-DR activation antigen was expressed on the coronary arterial endothelium at the infiltrates in which macrophages and T cells coexisted. In contrast, coronary arterial endothelium did not express HLA-DR antigens in the myocardial tissues of controls (n = 4). HLA-DR + endothelial cells may play an important role in the development of Kawasaki vasculitis.

A study on the optimal dose of aspirin therapy in Kawasaki disease. Clinical evaluation and arachidonic acid metabolism.

Aspirin is the basic treatment for Kawasaki disease, however its optimal dose is controversial. We investigated the therapeutic efficacy of high-dose (100 mg/kg/day, n = 30) versus low-dose (30 mg/kg/day, n = 30) aspirin. Duration of fever, transaminase, plasma thromboxane B2 (TxB2) and 6-keto-prostaglandin F1 alpha (PGF1 alpha) levels were compared before enrollment and on days 4, 7 and 14. In the high-dose group, duration of fever was significantly shorter than that of low-dose group (3.2 +/- 1.8 versus 5.4 +/- 4.3 days, p less than 0.05), however, serum glutamic pyruvic transaminase levels were elevated (157.4 +/- 187.7 versus 48.0 +/- 58.2I.U./liter, p less than 0.005). No differences in the incidence of coronary artery lesions were observed (5 of 30 versus 7 of 30). Plasma TxB2 production was completely blocked in both groups, plasma 6-keto-PGF1 alpha levels in the high-dose group on day 14 was lower than that in the low-dose group (39 +/- 26 versus 160 +/- 207 pg/ml, p less than 0.05). This latter observation suggest that high-dose therapy may be disadvantageous as anti-thrombotic treatment, and supports the notion that low dose therapy is safe in the acute stage of Kawasaki disease.

Plasma prostaglandin E 2 level in Kawasaki disease

Plasma levels of prostaglandin E 2 and prostaglandin F 2α were determined in 15 patients in the acute and recovery stages of Kawasaki disease, 10 patients with anaphylactoid purpura, 16 with bacterial and viral infections and 10 healthy children. Plasma levels of prostaglandin E 2 were markedly increased in the acute stage of Kawasaki disease, and these levels were decreased in the recovery stage. The prostaglandin F 2α/prostaglandin E 2 ratio in the acute stage of Kawasaki disease was markedly decreased. Plasma levels of prostaglandin E 2 in patients with anaphylactoid purpura, bacterial and viral infections were within the normal range. In Kawasaki disease which is associated with systemic vasculitis with a severe inflammatory reaction, prostaglandin E 2 is considered to be more selectively produced and released than prostaglandin F 2α, suggesting that prostaglandin E 2 plays an important role in the immunological and inflammatory reaction.

Hepatomegaly and splenomegaly in Kawasaki disease.

Pathologic studies of the liver were performed on 30 autopsied cases of Kawasaki disease. The cases were classified into four groups (stages I-IV), and stage IV was further divided into two subgroups according to the duration of the illness at the time of death. Liver weights were markedly increased in stage II (12-25 days) and in stage III (28-36 days) but returned to normal in stage IVb (7 months to 6 years). Likewise, spleen weights were also markedly increased in stages II and III. Stage I (0-9 days) and stage II were characterized by acute inflammation in portal area, and degree of inflammatory changes decreased gradually. There was significant correlation between hepatomegaly and the degree of inflammation in portal areas, but not with definite heart failure or the use of drugs. These data suggest that the pathogenesis of hepatomegaly in acute-stage Kawasaki disease involves the inflammation in portal areas and/or latent heart failure.