You have just invented a new wonder drug that has great biologic potential for a previously untreated skin disorder. Your drug is somewhat insoluble in water or oil, but with the help of a clever pharmacologist you develop and then optimize a vehicle for delivery of your drug through human skin and mill the finished product to a fine particle size for an elegant and, hopefully, stable preparation. Once in the marketplace, your product is reported to cause contact dermatitis and patch tests with the finished product are positive. You are asked to provide the individual ingredients for testing, but the report comes back that all individually tested ingredients were negative. The diagnosis is said to be "compound allergy." Your active ingredient, which you knew was not well absorbed without help, was dispersed in petrolatum, and no reactions were observed to explain the problem.
Good careful investigators have reported on the existence of compound allergy1-4; ie, positive patch test results to a whole product with negative patch test results to the individual ingredients. The most commonly asked question is whether a higher concentration
Rietschel RL. The Patch Test as an Exercise in Cutaneous PharmacokineticsDoes Compound Allergy Exist?. Arch Dermatol. 1992;128(5):678-679. doi:10.1001/archderm.1992.01680150108016