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Stratum Corneum Biomarkers of Skin Barrier and Immune Response in Patch Test Reactions to Common Contact Allergens and Irritants

Patch testing is a commonly used diagnostic tool for contact sensitization (CS), however it is associated with false-positive and false-negative outcomes. The patch test baseline series contains several hapten mixes in one patch test preparation. In case of a positive reaction to a mix, patch testing of the individual haptens is performed to identify the causative hapten(s). However, some subjects show a negative reaction in subsequent testing which might indicate a previous false-positive, possibly irritant reaction. As irritant and allergic reaction have different pathophysiology (CS is a type IV hypersensitivity reaction involving T-cells while activated innate immunity and skin barrier damage underlie skin irritation), we investigated whether suitable biomarkers might assist in discrimination between irritant and allergic reaction. In the present study, we determined various biomarkers of skin barrier and immune response in patch test to fragrances. We included 23 persons with previously positive patch test to at least one compound from the baseline fragrance mix I and II. These subjects underwent subsequent patch testing with the single fragrances. All allergens were applied in petrolatum that was also used as a control test site. 72 hrs after patch testing, samples of the stratum corneum (SC), the uppermost epidermal layer, were collected from the test sites by using adhesive tapes. In the SC tapes, 15 cytokines of different signature (Th1, Th-2 and innate markers) were determined by a multiplex immunoassay. Next, filaggrin degradation products (NMF) as an indicator of skin barrier damage were measured. From 23 tested subjects, seven had negative reaction after patch testing to a single fragrance. Of 15 detected cytokines, seven cytokines showed significant difference between a hapten and petrolatum (CCL17, CXCL10, CCL22, CXCL8, CCL2 and IL-22). We compared the sub-group of subjects who did not have a positive reaction to a single fragrance with the group who did show a positive reaction to both, mix and a single fragrance. A significant difference between these sub-groups was found for IL-16 and CXCL10. IL-16 has previously been shown as a biomarker to distinguish irritant from allergic reaction. In addition, a sub-group with negative patch test to a single fragrance showed decrease in NMF further supporting the hypothesis that the positive reaction to the mix was caused by an irritant reaction. This study confirms previous findings that IL-16 might be a suitable biomarker to distinguish irritant from allergic reaction. This might be of relevance in diagnostics of contact dermatitis and interpretation of allergen patch testing.

Patch testing, fragrance mix, haptens, stratum corneum, cytokines, natural moisturizing factor

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