Repeated Exposure to Hydroperoxides of Linalool Induces Immunologically Verified Allergic Contact Dermatitis

Background: Fragrance allergens are a leading cause of contact allergy (CA). Linalool, common in cosmetics and household products, forms sensitising hydroperoxides (Lin-OOH) upon air exposure. Lin-OOH is linked to a high prevalence (3.9%–11.7%) of positive patch test results, but often gives rise to doubtful or irritant reactions. Objectives: To reassess patch test concentrations of Lin-OOH, determine elicitation threshold under repeated exposure, and explore associated immunological responses. Methods: Patch testing was followed by a twice daily, 21 days repeated open application test (ROAT) using a Lin-OOH-containing simulated perfume at three different concentrations (blinded to the participants and the investigators). Twelve sensitised individuals with CA to Lin-OOH and 20 healthy controls were included. Skin biopsies from a subset were analysed via RT-qPCR. Results: Lin-OOH 1.0% was the most reliable patch test concentration to confirm CA in our patient cohort. Positive ROAT reactions occurred in 4/12 (33%) patients at 0.163% Lin-OOH (1630 ppm), 2/12 (17%) at 0.054% (538 ppm) and 1/12 (8%) at 0.018% (179 ppm); none in controls. Gene expression analysis showed upregulation of IL1 family members (IL1β and IL1RN), type 2 immune response (IL4 and GATA3) and chemokines (CCL22). Conclusions: Lin-OOH elicited dose-dependent reactions in sensitised individuals during both patch testing and simulated use (ROAT). Molecular profiling of biopsy samples confirmed activation of immune pathways consistent with CA to fragrances following patch testing.