The Role of Di(2-Ethylhexyl) Phthalate as an Exacerbating Factor in Chronic Spontaneous Urticaria

Phthalates are one of the most commonly used endocrine disruptors and have been considered a risk factor for respiratory disease including asthma. However, it is not yet known how they are related to urticaria. We investigated the association between phthalate exposure and urticaria in 10 healthy controls and 20 adult patients with active urticaria. The urinary levels of mono-n-butyl phthalate (MnBP), mono-2-ethyl-5-carboxypentyl phthalate (MECPP), mono-(2-ethyl-5-oxohexyl) phthalate, and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) were measured by using high performance liquid chromatography tandem mass spectrometry, and mast cell releasability was determined after phthalate treatment. The levels of phthalate metabolites, especially di-ethylhexyl phthalate (DEHP), are significantly increased in the urine of patients with urticaria compared to the healthy controls. The release of β-hexosaminidase in human mast cells is more significantly increased by MnBP, mono-benzyl phthalate, MEHHP, and MECPP compared to the negative controls; interestingly, the highest secretion of β-hexosaminidase is observed after the lowest stimulation of MECPP. Phthalates, including DEHP, may act as aggravating factors for chronic spontaneous urticaria and can be used as potential therapeutic targets in future studies.