title: The association between phthalate exposure and atopic dermatitis with a discussion of phthalate induced secretion of interleukin-1β and thymic stromal lymphopoietin.
abstract: Phthalate diesters are widely used as emollients in plastic and cosmetics as well as in food packaging and perfumes, potentially leading to prolonged and repeated dermal, oral and airborne exposure. We here review published articles that have evaluated the putative role of phthalate diesters in the pathogenesis of atopic dermatitis and discuss possible pathogenic pathways. A literature search resulted in 563 articles in Embase and 263 articles in Pubmed. After identification of relevant articles based on screening of titles, abstracts and reference lists, a total of 39 articles were selected and included. While no clear association has been shown between systemic phthalate levels and atopic dermatitis in human studies, animal data suggests that phthalates may worsen dermatitis and in vitro data suggests that interleukin-4 could be upregulated. Moreover, both loss-of-function mutations in the filaggrin gene and atopic dermatitis have been associated with elevated systemic phthalate levels. There is a need for prospective studies to clarify the possible pathogenic role of phthalate diesters in atopic dermatitis and the associated health risk, especially with the general trend towards barrier restoration with emollients in infants at risk of developing atopic dermatitis. In summary, we conclude that the results from published studies are controversial and inconclusive.
authors.affiliation: a National Allergy Research Centre, Department of Dermato-Allergology , Copenhagen University Hospital Gentofte , Copenhagen , Denmark.
authors.forename: Line E K
authors.initials: LE
authors.lastname: Overgaard
authors.affiliation: b Department of Immunology and Microbiology , University of Copenhagen , Copenhagen , Denmark.
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Bonefeld
authors.affiliation: c Department of Growth and Reproduction, Rigshospitalet , University of Copenhagen , Copenhagen , Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Frederiksen
authors.affiliation: c Department of Growth and Reproduction, Rigshospitalet , University of Copenhagen , Copenhagen , Denmark.
authors.forename: Katharina M
authors.initials: KM
authors.lastname: Main
authors.affiliation: a National Allergy Research Centre, Department of Dermato-Allergology , Copenhagen University Hospital Gentofte , Copenhagen , Denmark.
authors.forename: Jacob P
authors.initials: JP
authors.lastname: Thyssen
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D003876:Dermatitis, Atopic / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*; D004781:Environmental Exposure / Q000009:adverse effects; D000091344:Filaggrin Proteins; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics; D010795:Phthalic Acids / Q000009:adverse effects / Q000378:metabolism*; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D053583:Interleukin-1beta; D007381:Intermediate Filament Proteins; D010795:Phthalic Acids; D015847:Interleukin-4; C032279:phthalic acid; D000094632:Thymic Stromal Lymphopoietin
keywords: Atopic dermatitis; IL-1β; TSLP; endocrine disruptors; filaggrin; phthalate