Contact dermatitis with negative patch tests: the additive effect of allergens in combination

We deduced on theoretical grounds that conventional patch testing would be inadequate for the detection of sensitivity to multiple allergens. Fourteen patients with positive patch tests to two unrelated allergens were studied and the response to those two allergens was measured when tested singly or in combination, using 10 different pair combinations from 15 common allergens. With serial dilutions in chloroform (14 patients) and paraffin (four patients), the response was related to the log-dose of the allergen, and change in skin-fold thickness corresponded well with clinical grading. Single allergens diluted below the threshold for a patch-test response gave a response when given in combination, the threshold for a response to one allergen being lowered by the presence of another. On the linear part of the dose-response curves the response to the mixture of allergens was additive, the combined response being the sum of the individual components. Approaching the plateau region the response to the combination was greater than to the individual allergens but less than the sum of the single responses. The same results were obtained with allergens in paraffin. We conclude that conventional single allergen patch testing by itself is inadequate for the diagnosis of contact dermatitis.