Skin sensitizing properties of arylalcanoic acids and their analogues

While participating in a clinical trial of suprofen, a new antiphlogistic agent, a 32-year-old atopic woman developed a severe contact dermatitis reaction of the hands to this substance. To check for cross-reactivity patterns, patch tests were performed with similar arylalcanoic acid derivatives. Positive reactions were obtained for ibuprofen, ketoprofen, fenoprofen, naproxen, alclofenac, and metiazinic acid, which are all antiphlogistic and anti-inflammatory agents for systemic use, and chlorambucil, which is an antineoplastic agent. The antigenic determinant seems to correspond to a very well-defined structure: the carboxyl group (-COOH) has to be separated from the aryl structure by at least one C atom (substituted or not). Furthermore, the aryl group must be substituted with different chemical groups but not in the orthopositions.