Allergic contact dermatitis: epidemiology, molecular mechanisms, in vitro methods and regulatory aspects

Abstract

Contact allergies are complex diseases, and one of the important challenges for public health and immunology. The German ‘Federal Institute for Risk Assessment’ hosted an ‘International Workshop on Contact Dermatitis’. The scope of the workshop was to discuss new discoveries and developments in the field of contact dermatitis. This included the epidemiology and molecular biology of contact allergy, as well as the development of new in vitro methods. Furthermore, it considered regulatory aspects aiming to reduce exposure to contact sensitisers. An estimated 15–20% of the general population suffers from contact allergy. Workplace exposure, age, sex, use of consumer products and genetic predispositions were identified as the most important risk factors. Research highlights included: advances in understanding of immune responses to contact sensitisers, the importance of autoxidation or enzyme-mediated oxidation for the activation of chemicals, the mechanisms through which hapten-protein conjugates are formed and the development of novel in vitro strategies for the identification of skin-sensitising chemicals. Dendritic cell cultures and structure-activity relationships are being developed to identify potential contact allergens. However, the local lymph node assay (LLNA) presently remains the validated method of choice for hazard identification and characterisation. At the workshop the use of the LLNA for regulatory purposes and for quantitative risk assessment was also discussed.

In Vivo Expansion of Endogenous Regulatory T Cell Populations Induces Long-Term Suppression of Contact Hypersensitivity

“…The prevalence of allergic contact dermatitis is ascending worldwide, with 15-20% of the general population exhibiting this allergic disorder, rendering it a significant challenge to public health systems (2). Prevention of exposure to contact sensitizers and topical corticosteroid application remain the main treatment strategies currently used.…”

Piper nigrum Fruit Extract Prevents TMA-Induced Allergic Contact Dermatitis by Regulating Th2 Cytokine Production

“…During this step, a variety of immune cells including Langerhans cells, dermal dendritic cells, T lymphocytes, and keratinocytes are involved in the immune response and eventually cause skin inflammation (Honda et al, 2013). Globally, 15-20% of the general public suffers from the symptoms of ACD including pruritus and pain (Peiser et al, 2012). Although the pharmacological agents cortisol, prednisolone, and dexamethasone are used for the treatment of allergies, inflammation, and autoimmune disorders, the side effects of these drugs have driven attempts to develop more effective immune modulating agents (Berthelot et al, 2013).…”

“…Allergic contact dermatitis (ACD) arises from a delayed type IV hypersensitivity response and is one of the most common skin diseases, affecting 15-20% of the general population worldwide (Peiser et al, 2012). Compounds lower than 500 daltons have been observed to penetrate through the stratum corneum barrier of epidermal skin, where they become haptens (Martin, 2004).…”

An economic approach to non-animal toxicity testing for skin sensitisation

“…Determining the societal gains and losses from releasing a hazardous or a non-hazardous substance requires estimating expected marketing benefits, and balancing them with expected direct and indirect health damage costs caused by ACD. The latter is assumed to be a function of the skin sensitisation prevalence of a substance (Schnuch et al, 2011;Peiser et al, 2012;Schnuch et al, 2012) within the EU. As a proof-of-concept case, the Bayesian VOI model is applied to the preservative Methylisothiazolinone which is used for the formation of Kathon CG, known which is an ingredient for cosmetic products with high skin sensitisation prevalence (Uter et al, 2013).…”

“…contact (UNECE, 2011), from which about 15% to 20% of the population suffers at least once in a lifetime with increasing prevalence (Thyssen et al, 2007;Peiser et al, 2012). Responding to the urgent need to minimise animal testing, several non-animal testing methods and integrated testing strategies have been developed (Mehling et al, 2012;Reisinger et al, 2015;Urbisch et al, 2015a).…”