Assessment of contact allergen cross-reactivity by retesting

At former allergic contact dermatitis reaction sites retesting causes augmented hyper-reactivity, characterized by an accelerated onset within a few hours. This expression of 'local skin memory' has been ascribed to locally persisting allergen-specific effector/memory T cells. To verify this hypothesis, we investigated whether accelerated retest reactivity also occurs with cross-reactive allergens. Guinea pigs were immunized with either or both 2,4-dinitrochlorobenzene (DNCB) and 2-hydroxyethyl methacrylate (HEMA), and primary skin tests to these and cross-reactive methacrylic compounds were performed 12-21 days later. Subsequently, new skin tests were conducted 3 weeks later both at the former test ('retest') and contralateral, non-pretreated test ('control') sites, and skin test readings started 2 h later. Retest reactivity was evaluated by comparing retest and contralateral control reactions. Both contact sensitizers, HEMA and DNCB, induced strong retest reactivity, peaking at 4-6 h. Fully allergen-specific retest reactivity was observed when primary skin tests had been postponed until 21 days after immunization, most probably reflecting loss of accumulation of irrelevant allergen-primed T cells at that time. As hypothesized, retesting with various methacrylate congeners at primary HEMA, but not DNCB, skin test sites showed early hyperreactivity strengths in line with those observed earlier in conventional cross-reactivity studies. These results, therefore, support the view that local skin memory exhibits allergen specificity through residual allergen-primed T cells. Because the retesting procedure is readily applicable in clinical practice, it provides a tool not only for confirmation of doubtful contact allergic skin reactions, but also for distinguishing between true cross-reactivity and coincident multiple sensitization in man.