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The aim of our study was to describe demographic features, causative agents, clinical features, treatments and outcomes of children suffering from acute FPIES at three Italian of Pediatric Allergology Centers. A retrospective study was performed over a 7-year period (2004�C2010). Tolmetin Hospital medical record databases and hospital outpatient electronic charts were screened for the diagnosis of FPIES. Information on the first and subsequent FPIES' episodes was collected. We diagnosed 66 children with FPIES. The number of diagnoses significantly increased between 2008 and 2010 (P?ubiquitin-Proteasome degradation increase in the FPIES diagnosis has been observed in the last few years. We also discussed selected management aspects of this syndrome where different phenotypes can be found. DAPT secretase ""Cite this as: D. G. Powe, A. J. Bonnin and N. S. Jones, Clinical & Experimental Allergy, 2010 (40) 987�C997. Allergy is defined as an immediate hypersensitivity type I immunological disease, which can be IgE or non-IgE driven, and in the latter case may be antibody or cell mediated. Atopy is a term used to describe individuals with a genetic predisposition for developing IgE-mediated allergic disease. But more recently, it has become evident that IgE-mediated disease can occur in non-atopic subjects. While it is now generally accepted that mucosal local IgE has a role in the expression of atopic allergic disease, the concept of ��local allergy�� in non-atopic subjects has been proposed, with the term ��entopy�� given to this condition. Although there is increasing evidence supporting this paradigm, entopy is only applicable to a proportion of non-atopic patients, suggesting that other disease mechanisms exist to explain non-atopic disease. This review considers the evidence for local mucosal allergy in atopic and non-atopic individuals with an emphasis on diseases affecting the upper airways and eye.