The Risk of Sensibilization and Contact Urticaria upon Topical Application of Fumaric Acid Derivatives

Abstract

Systemic and sometimes topical therapy with fumaric acid (FA) and its derivatives is used in the treatment of psoriasis. Scattered data show that the topical application of these derivatives elicits side effects. Application of FA and some derivatives on the skin was accompanied by perilesional skin irritation, macular papular rashes and urticarial reactions. In order to determine the irritating and sensitizing properties of FA derivatives we used a cytotoxicity, flank irritation, ear swelling and guinea pig maximization test. The results of the cytotoxicity test demonstrated that dimethylfumarate (DMF) was the most toxic derivative. DMF induced also contact-urticarial reactions in contrast to mono-ethylfumarate (MEF). Challenge experiments with FA, MEF and DMF in MEF- and DMF-sensitized guinea pigs demonstrated that both MEF and DMF are moderate contact sensitizers. In DMF-sensitized animals cross-reactions with MEF were found. As DMF and MEF have cytotoxic, contact-urticarial and/or sensitizing properties, topical application should be avoided.

The critical review of methodologies and approaches to assess the inherent skin sensitization potential (skin allergies) of chemicals Part II

“…Dimethyl fumarate is generally used as a systemic antipsoriasis drug (40, 41). It is also a well‐known contact allergen, together with other fumaric acid esters (42, 43). In the case of ‘furniture dermatitis', it was used as a volatile antifungal agent concealed in the finished products such as furniture, textiles, and shoes (44–50).…”

Wire Melt Electrospinning of Thin Polymeric Fibers via Strong Electrostatic Field Gradients

“…The large quantity of solvent (relative to the polymer) required to achieve sufficiently low viscosity for solution electrospinning increases the fabrication costs of nanofibers. Moreover, the solvents used are often toxic and the environmental footprint left from solvent evaporation can be highly unattractive for industrial‐scale production . Also, the presence of residual solvent in the as‐spun product can become a barrier for entry to market in certain applications, such as water filtration, requiring post‐electrospinning modifications to extract the residual solvent.…”

Determination of Dimethyl Fumarate and Other Fumaric and Maleic Acid Diesters in Desiccants and Consumer Products in Japan

“…3) On the other hand, DMF is cytotoxic (epidermoid cell line A431, LD 50 : 5.04 µg/ml), and it induces nonimmunological contact urticaria and allergic contact dermatitis. 4) Since the summer of 2006, many dermatitis * To whom correspondence should be addressed: Division of Environmental Chemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. Tel.…”