Contact dermatitis: from pathomechanisms to immunotoxicology

Abstract

Contact allergens are small reactive chemicals. They cause allergic contact dermatitis (ACD) by activating the innate and adaptive immune system. Contact allergens are very peculiar because of their built-in autoadjuvanticity that allows them to trigger sterile inflammation following skin penetration. The innate inflammatory response involves the triggering of pattern recognition receptors either by direct chemical interaction with such receptors or by induction of endogenous activators. I discuss here the recent findings regarding prevalence and predisposition, the identification of innate immune and stress response mechanisms relevant for sensitization and the orchestration of the innate and adaptive immune response to contact allergens. Despite still significant gaps of knowledge, recent advances in our understanding of the immunopathogenesis of ACD can now be used for the development of causative treatment strategies and of in vitro alternatives to animal testing for the identification of contact allergens in immunotoxicology.

Advanced tests for skin and respiratory sensitization assessment

“…Recent studies have shown clearly that contact allergens have autoadjuvant effects that lead to the efficient activation of the innate immune system, provoking skin inflammation, even in germ-free mice (Martin et al, 2011;Martin, 2012;Kaplan et al, 2012). In addition, they form t-cell epitopes that lead to ACD.…”

“…Blocking one of those interconnected pathways interrupts the sensitization process and, in some cases, also prevents elicitation of CHS in successfully sensitized mice. this may result in the development of causative treatments for patients with ACD (Martin et al, 2011;Martin, 2012).…”

“…Moreover, the result from a formulation may be different. If there are, for example, three weak contact allergens in a final product or weak contact allergens plus an irritant substance, a threshold may be overcome that allows for successful sensitization by the allergenic mixture (Martin, 2012).…”

Fas Receptor: An Overview

“…13,[57][58][59][60] Activated transcription factors, such as nuclear factor kappa B (NF-κ B), activator protein 1 (AP-1), nuclear factor of activated T-cells (NF-AT) and signal transducer and activator of transcription (STAT) factors, induce inflammation and favor the recruitment of CLA + T cells to the skin through chemokines and cell-adhesion molecules (e.g. vascular-cell adhesion molecule 1 and E-selection).…”

Contact Allergy in Atopic Patients: What We Suspected and What We Know

“…The relationship between AD and ACD remains unclear, although AD is characterized by T-helper (Th) cell 2 phenotype in mainly the acute phase, with additional roles for Th1, Th17, and Th22 cells in chronic disease [10]. ACD is being increasingly recognized as a Th17-and Th22-polarized response in addition to a classic Th1 response [11]. Because of the relatively wide overlap of AD and ACD, it is important to include patch testing in the diagnostic battery of physicians caring for children with AD.…”