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Background Atopic dermatitis ( AD) and psoriasis patients are frequently colonized with Staphylococcus aureus ( S. aureus) that produce the staphylococcal exotoxin α-toxin. However, only patients with AD suffer from bacterial superinfections with this pathogen, which implicates immunological differences in AD vs psoriasis in combating these bacteria. S. aureus recognition is partially mediated by intracellular nucleotide-binding oligomerization domain receptors ( NLRs), which link α-toxin to caspase-1 activation through the formation of the NLRP3 inflammasome and to IL-1β secretion. Objective To investigate (i) NLRP3 expression in the context of different T-helper cytokine milieus and (ii) its function in response to sublytic α-toxin stimulation in patients with AD and psoriasis compared with healthy controls. Methods NLRP3 expression and function were investigated in lesional AD and psoriasis skin as well as in primary keratinocytes (HPKs) and monocytes upon stimulation with Th1, Th2, Th17 and Th22 cytokines or staphylococcal α-toxin, respectively, at the mRNA and protein (ELISA, immunohistochemistry and immunofluorescence) level. Results NLRP3 and caspase-1 expressions were reduced in lesional AD skin compared to psoriatic and healthy skin. IL-4, IL-5 and IL-13 downregulated NLRP3 and ASC, whereas interferon-γ upregulated NLRP3 in HPKs. In monocytes, caspase-1 expression was reduced by Th2 cytokines and enhanced by a Th1 milieu. Caspase-1-dependent IL-1β secretion was impaired in monocytes from patients with AD compared to patients with psoriasis and healthy controls by α-toxin stimulation following priming with lipoteichoic acid. Conclusion Impaired NLRP3 expression and function may partially explain how skin colonization and infection with S. aureus can contribute to chronic skin inflammation in AD. [ABSTRACT FROM AUTHOR]

Aims: The presence of micrometastases in the sentinel lymph node (SLN) is an important prognostic parameter for melanoma patients. The aim was to determine the prognostic relevance of histopathological characteristics of micrometastases in the SLN, which has not been adequately addressed thus far. Methods and results: In 169 melanoma patients with positive SLN, histopathological features of the SLN were correlated with overall survival (OS) and relapse-free survival (RFS). Tumour burden, expansion of melanoma cells in the periphery (infiltration of capsule) and towards the centre of the SLN [tumour penetrative depth (TPN)] were of prognostic significance for OS and RFS on univariate analysis. Multivariate analysis revealed three independent significant parameters which predict a poor prognosis: presence of infiltration of the SLN capsule, TPN ≥ 2 mm and size of the largest tumour deposit ≥ 30 cells. Conclusions: Histopathological analysis of SLN allows the identification of patients with a poor prognosis depending on the location of melanoma cells and tumour burden. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Prognostic significance of histopathological parameters in sentinel nodes of melanoma patients," by I. Satzger and colleagues in the 2007 issue.