The relationships between exposure dose and response in induction and elicitation of contact hypersensitivity in humans.

Like all physiological systems, the human immune system exhibits dose-response relationships in its reactions. The strength of sensitization is related to the potency of the immunogen and the dose that reaches the immune system. In skin, as sensitizing dose per unit area (mug cm(-2)) is increased on a log scale, there is a sigmoid dose-response curve for subsequent reactivity. Similarly, the response to elicitation shows a classical sigmoid response to increasing challenge dose, with the dose per unit area again being the determinant. There is a clear inverse correlation between the strength of sensitization and the subsequent dose of antigen to which an individual will respond. This is reflected in the different challenge systems used to diagnose the existence of allergic contact sensitization to a given allergen. The occluded patch test aims to use the highest concentration possible to detect the weakest degrees of allergy, whereas the repeated open application test uses much lower concentrations similar to those encountered in real life, applied repeatedly but without occlusion, to assess clinical relevance. Many authors have attempted to use the lowest concentrations to which rare, highly sensitized individuals can react to define the concentrations which might be free of risk in terms of inducing allergic sensitization. However, it is clear that the dose-response relationships for induction of sensitivity by repeated low-dose exposures must be carefully defined in future studies. This article reviews the dose-response relationships of human contact sensitization.