Congenital telangiectatic atrophic patch on a healthy child.

BACKGROUND: Rapidly involuting congenital hemangiomas (RICHs) are rare vascular tumors that have a proliferative phase in utero, present fully grown at birth, and have a fast involution phase after birth. Even rarer cases have completed involution in utero and present at birth as an atrophic plaque with redundant skin. CASE REPORT: We present one case of a RICH that underwent involution in utero and revise the diagnostic and management implications.

Repeated systematic surveillance of Kawasaki disease in Ontario from 1995 to 2006.

BACKGROUND: Rising incidences of Kawasaki disease (KD) have been reported worldwide. Reported herein are the results of 4 triennial KD surveillances conducted in Ontario. METHODS: Between 1995 and 2006 all hospitals in Ontario were asked on 4 occasions to identify all patients with discharge diagnoses of KD and report incident cases. RESULTS: The latest surveillance identified 697 new KD patients (100% response rate) for a total of 2378 KD patients through all 4 surveillances. Yearly incidence was 26.2/100,000 for <5 years old, 6.7/100,000 for 5-9 years old and 0.9/100,000 for 10-14 years old. KD incidence significantly increased from 1995 to 2006, although the increase seemed to plateau between the 3rd and 4th surveillance. There was an increase in the proportion of patients diagnosed with incomplete KD and a significant reduction in the rate of coronary artery abnormalities, possibly due to better disease recognition and treatment. Hospitals reporting <20 cases per surveillance were found to be more likely to report cases with incomplete KD. These patients were also less likely to be treated with i.v. immunoglobulin and aspirin but were more likely to be treated with antibiotics, suggesting uncertainties regarding diagnosis and management of KD patients in those centers. CONCLUSIONS: The incidence of KD in Ontario is possibly one of the highest outside of Asia and has been rising since 1995. Although the most recent surveillance demonstrated improved cardiac outcomes, treatment delays or absence thereof continue to be a problem. Effective diagnosis and prompt treatment remain critical aspects of KD management.

Arthritis presenting during the acute phase of Kawasaki disease.

OBJECTIVE: To define the prevalence, pattern, and clinical course of arthritis presenting at the time of diagnosis of Kawasaki disease. STUDY DESIGN: A single-center, retrospective study of 414 consecutive patients diagnosed with Kawasaki disease between January 1997 and December 2002 was performed. Standardized clinical assessments, laboratory and imaging test results, and treatment regimens were reviewed. The clinical, laboratory, treatment response, and coronary outcome data were analyzed for children with and without arthritis. RESULTS: The prevalence of arthritis was 7.5% (31/414). In the 31 children with arthritis, 55% had oligoarticular involvement and 45% had polyarticular involvement. In both of these groups, the large joints were predominantly involved. Some 88% of the children with arthritis responded to standard intravenous immunoglobulin therapy for acute Kawasaki disease and did not require additional medications. The children with arthritis had significantly increased levels of inflammatory markers, but their demographical and clinical features were otherwise similar to those of the children without arthritis, including coronary outcome, with the same proportion (13%) of children from each group having coronary artery lesions (z-score > or = 2.5). CONCLUSIONS: Arthritis is a short-lived phenomenon included in the clinical spectrum of acute Kawasaki disease. Children with arthritis have evidence of increased systemic inflammation but otherwise share the same clinical features, response to treatment, and coronary outcomes as patients without arthritis. Most cases of arthritis resolve without additional therapeutic intervention.

Enterohemorrhagic Escherichia coli O157:H7 disrupts Stat1-mediated gamma interferon signal transduction in epithelial cells.

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a clinically important bacterial enteropathogen that manipulates a variety of host cell signal transduction cascades to establish infection. However, the effect of EHEC O157:H7 on Jak/Stat signaling is unknown. To define the effect of EHEC infection on epithelial gamma interferon (IFN-gamma)-Stat1 signaling, human T84 and HEp-2 epithelial cells were infected with EHEC O157:H7 and then stimulated with recombinant human IFN-gamma. Cells were also infected with different EHEC strains, heat-killed EHEC, enteropathogenic E. coli (EPEC) O127:H6, and the commensal strain E. coli HB101. Nuclear and whole-cell protein extracts were prepared and were assayed by an electrophoretic mobility shift assay (EMSA) and by Western blotting, respectively. Cells were also processed for immunofluorescence to detect the subcellular localization of Stat1. The EMSA revealed inducible, but not constitutive, Stat1 activation upon IFN-gamma treatment of both cell lines. The EMSA also showed that 6 h of EHEC O157:H7 infection, but not 30 min of EHEC O157:H7 infection, prevented subsequent Stat1 DNA binding induced by IFN-gamma, whereas infection with EPEC did not. Immunoblotting showed that infection with EHEC, but not infection with EPEC, eliminated IFN-gamma-induced Stat1 tyrosine phosphorylation in both dose- and time-dependent fashions and disrupted inducible protein expression of the Stat1-dependent gene interferon regulatory factor 1. Immunofluorescence revealed that EHEC infection did not prevent nuclear accumulation of Stat1 after IFN-gamma treatment. Also, Stat1 tyrosine phosphorylation was suppressed by different EHEC isolates, including intimin-, type III secretion- and plasmid-deficient strains, but not by HB101 and heat-killed EHEC. These findings indicate the novel disruption of host cell signaling caused by EHEC infection but not by EPEC infection.

Escherichia coli shiga-like toxins induce apoptosis and cleavage of poly(ADP-ribose) polymerase via in vitro activation of caspases.

Shiga-like toxin-producing Escherichia coli causes hemorrhagic colitis and hemolytic-uremic syndrome in association with the production of Shiga-like toxins, which induce cell death via either necrosis or apoptosis. However, the abilities of different Shiga-like toxins to trigger apoptosis and the sequence of intracellular signaling events mediating the death of epithelial cells have not been completely defined. Fluorescent dye staining with acridine orange and ethidium bromide showed that Shiga-like toxin 1 (Stx1) induced apoptosis of HEp-2 cells in a dose- and time-dependent manner. Stx2 also induced apoptosis in a dose-dependent manner. Apoptosis induced by Stx1 (200 ng/ml) and apoptosis induced by Stx2 (200 ng/ml) were maximal following incubation with cells for 24 h (94.3% +/- 1.8% and 81.7% +/- 5.2% of the cells, respectively). Toxin-treated cells showed characteristic features of apoptosis, including membrane blebbing, DNA fragmentation, chromatin condensation, cell shrinkage, and the formation of apoptotic bodies, as assessed by transmission electron microscopy. Stx2c induced apoptosis weakly even at a high dose (1,000 ng/ml for 24 h; 26.7% +/- 1.3% of the cells), whereas Stx2e did not induce apoptosis of HEp-2 cells. Thin-layer chromatography confirmed that HEp-2 cells express the Stx1-Stx2-Stx2c receptor, globotriaosylceramide (Gb3), but not the Stx2e receptor, globotetraosylceramide (Gb4). Western blot analysis of poly(ADP-ribose) polymerase (PARP), a DNA repair enzyme, demonstrated that incubation with Stx1 and Stx2 induced cleavage, whereas incubation with Stx2e did not result in cleavage of PARP. A pan-caspase inhibitor (Z-VAD-FMK) and a caspase-8-specific inhibitor (Z-IETD-FMK) eliminated, in a dose-dependent fashion, the cleavage of PARP induced by Shiga-like toxins. Caspase-8 activation was confirmed by detection of cleavage of this enzyme by immunoblotting. Cleavage of caspase-9 and the proapoptotic member of the Bcl-2 family BID was also induced by Stx1, as determined by immunoblot analyses. We conclude that different Shiga-like toxins induce different degrees of apoptosis that correlates with toxin binding to the glycolipid receptor Gb3 and that caspases play an integral role in the signal transduction cascade leading to toxin-mediated programmed cell death.