Immunological, chemical and clinical aspects of exposure to mixtures of contact allergens

Abstract

SummaryAllergic contact dermatitis is one of the most frequent forms of skin inflammation. Very often, we are exposed to mixtures of allergens with varying potencies, doses/areas, and exposure times. Therefore, improved knowledge about immune responses to combinations of contact allergens is highly relevant. In this article, we provide a general introduction to immune responses to contact allergens, and discuss the literature concerning immune responses to mixtures of allergens. According to the existing evidence, increased responses are induced following sensitization with combinations of allergens as compared with single allergens. The response to a mixture of allergens can be both additive and synergistic, depending on the dose and combination of allergens. Importantly, sensitization with combinations of either fragrance allergens or metal salts can result in increased challenge responses to specific allergens within the mixture. Taken together, the immune responses to mixtures of allergens are complex, and further studies are required to obtain the necessary knowledge to improve consumer safety.Key words: fragrances; hair dyes; metals; mixtures of allergens.Contact allergy is very frequent in the European population, as shown by Diepgen et al., who found that 27% were sensitised to common allergens (1). This may lead to allergic contact dermatitis if exposure exceeds the individual threshold of response.The allergic response is frequently directed towards nickel, cobalt, fragrances, hair dye chemicals, or preservatives. Many of these molecules are categorized as weak to moderate allergens -this term will be used throughout the article for (pre/pro)haptens (2). Surprisingly, even 'weak to moderate' allergens do induce allergic contact dermatitis in many people. This indicates that exposure parameters, such as dose and exposure frequency, are critical. Interestingly, consumers are rarely exposed to one isolated allergen, but are more often exposed to mixtures of allergens, for example in the form of metal alloys, cosmetics, and cleaning agents (3, 4). The impact of being exposed to a mixture of allergens instead of a single allergen has not been well studied. Studies from our group have suggested that exposure to mixtures of allergens has a great impact on the immune responses to single allergens within the mixture. In this review, we will discuss the current knowledge on how exposure to mixtures of contact allergens affects the immune system by (i) altering the chemical properties of single allergens in the mixtures, (ii) changing the inflammatory response, and (iii) affecting T cell activation, proliferation, and differentiation. Furthermore, we will discuss other factors, such as the presence of irritants, a disrupted skin barrier, local skin inflammation, and local skin memory, that could increase the response to allergens. Finally, we will discuss the clinical impact of

Contact allergy to hair cosmetic allergens in Thailand

“…However, previous co‐exposure and independent sensitization to both substances could not be ruled out because concomitant reactions to m ‐aminophenol and hydroquinone were also identified . Moreover, the effects of sensitization with combinations of allergens in hair dyes should be considered . There was some evidence that allergic responses in patients might increase after exposure to combined allergens in hair dyes compared with single exposure to allergens …”

“…Moreover, the effects of sensitization with combinations of allergens in hair dyes should be considered . There was some evidence that allergic responses in patients might increase after exposure to combined allergens in hair dyes compared with single exposure to allergens …”

The role of skin barrier in occupational contact dermatitis

“…Most contact allergens have irritant properties and consequently an intrinsic potential to activate an innate immune response, whereas the strength of the irritant effect determines the strength of the allergic potential . Along these lines, exposure to a mixture of contact allergens also increases the risk of ACD, the so‐called cocktail effect …”

Evaluation of in vitro testing strategies for hazard assessment of the skin sensitization potential of “real‐life” mixtures: The case of henna‐based hair‐colouring products containing p‐phenylenediamine

“…On the basis of wash fastness and degree of permanence in the capillary fibre, synthetic hair dye‐based products available on the market are classified as bleaches (composed of hair‐lightening agents such as hydrogen peroxide), gradual (using metallic ingredients such as salts of lead, bismuth, or silver), temporary (water‐soluble ingredients that are easily washed out in one shampoo rinse), semipermanent (which can withstand washing six to eight times), and permanent (a category that represents ~80% of all colourants that are hardly removable by shampooing, because they penetrate deeply into the hair shaft) . These cosmetics may contain combinations of >100 different substances, for example, dyes, couplers, and fragrances; therefore, they are complex mixtures of a wide range of synthetic compounds, many of them with potential skin sensitization properties . Among these chemicals, the aromatic amine p ‐phenylenediamine (PPD) is a cost‐effective hair dye that is widely used, specifically in semipermanent and permanent products; however, it is frequently associated with contact sensitivity reactions in humans after the use of hair colourants .…”