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.

What's new in atopic eczema? An analysis of systematic reviews published in 2016. Part 2: Epidemiology, aetiology and risk factors

“…Conflicting results were found for an association between exposure to phthalate diester and AE in 5 animal and 12 human studies (3 prenatal and 9 postnatal) . Phthalate diesters are immunomodulatory chemicals in widespread use as plasticizers (added to soften and increase flexibility of plastics) and are also added to some cosmetics and perfumes.…”

Evaluation of the Occurrence of Phthalates in Plastic Materials Used in Food Packaging

“…Several studies (Table 5) revealed that phthalates and the ester derivative are passively ingested from the general environment, foods, drinks, breathing air, and dairy life products, causing various dysfunctions [3,20,30,31,34,[37][38][39][40][41][42][43][44][45][46]. Exposures to DEHP, BBP, DBP, and DEP are associated with dermatitis, conjunctivitis, and allergic symptoms [47]. Other studies have found a relationship of asthma and worsening of pulmonary functions with these phthalates [48].…”

Atopic Eczema: Genetic Associations and Potential Links to Developmental Exposures

“…Mechanistically, it appears that phthalates may induce IL-4 and IL-1 family cytokines, which, when taken together, is in line with the T H 2 pro-inflammatory cytokine response seen in AD/AE. 109 However, as with many other environmental exposures, there are studies that find no relationship between developmental phthalate exposure and the development of allergic disease. It is evident that similar to other chemicals used in plastics, such as the more media-hyped bisphenol A, more clinical cohort studies are needed to solidify any links between in utero phthalate exposures and AD/AE development.…”