fumarates and Drug-Hypersensitivity

In 12 healthy volunteers the topical application of monoethyl fumarate caused a spontaneous persistent erythema. Systemic application induced flush. In urticaria pigmentosa the influence was significant higher than in normal skin. This fact suggests a mast cell degranulation caused by monoethyl fumarate.

Topics: Administration, Oral; Adolescent; Adult; Aged; Cell Degranulation; Drug Hypersensitivity; Female; Fumarates; Humans; Male; Mast Cells; Middle Aged; Patch Tests; Randomized Controlled Trials as Topic; Skin Tests

Di-n-butyl phthalate (DBP), a phthalate ester, has been shown to have an adjuvant effect on fluorescein isothiocyanate (FITC)-induced contact hypersensitivity (CHS) mouse models. Di-n-butyl maleate (DBM), widely used as a plasticizer for industrial application, has been reported to cause dermatitis in humans. DBM is a butyl alcohol ester of di-carboxylic acid that represents a part of the DBP structure, while di-n-butyl fumarate (DBF) is a trans isomer of DBM. We examined whether DBM or DBF exhibits an adjuvant effect like DBP does. When BALB/c mice were epicutaneously sensitized with FITC in the presence of DBM or DBF, the FITC-specific CHS response was enhanced, as we have observed for DBP. As to underlying mechanisms, DBM and DBF facilitated the trafficking of FITC-presenting CD11c(+) dendritic cells (DCs) from skin to draining lymph nodes and increased the cytokine production by draining lymph nodes. In conclusion, DBM and DBF may have an effect that aggravates contact dermatitis through a skin sensitization process.

Topics: Animals; Cytokines; Dermatitis, Contact; Drug Hypersensitivity; Fluorescein-5-isothiocyanate; Fumarates; Gene Expression Regulation; Lymph Nodes; Maleates; Mice; Mice, Inbred BALB C; Molecular Structure