Allergens in combination have a synergistic effect on the elicitation response: a study of fragrance-sensitized individuals

Perfume ingredients were chosen as model substances to study the effect of allergens in combination on the elicitation response. Two groups of eczema patients were studied. One consisted of 18 subjects with a contact allergy to two fragrance substances and the other was a control group of 15 subjects allergic to only one of the same two fragrance substances. The test and matched control subject were patch tested in exactly the same way with two allergens applied in serial dilution in separate chambers on one side and combined in one chamber on the other side of the upper back. The assessment of reactions was carried out on day 3 by clinical grading and laser Doppler flowmetry, and the extent of the reaction was measured in millimetres. The data were analysed by logistic dose-response models. It was found that the combination of two allergens in individuals allergic to both substances had a synergistic effect on the elicitation response evaluated by all three methods. The 1 : 1 mixtures of the two allergens elicited responses as if the doses were three to four times higher than those actually used, which is significantly more than expected if an additive effect had been present. In the control group, no increased response was seen to the combined allergens compared with the allergens tested separately. The synergistic effect demonstrated is likely to apply to other contact allergens as well and should be taken into account in designing diagnostic tests and performing safety assessments.