Allergic Contact Dermatitis - Pathophysiology

Pathophysiology

ACD arises as a result of two essential stages: an induction phase, which primes and sensitizes the immune system for an allergic response, and an elicitation phase, in which this response is triggered (Kimble et al. 2002). As such, ACD is termed a Type IV delayed hypersensitivity reaction involving a cell-mediated allergic response. Contact allergens are essentially soluble haptens (low in molecular weight) and, as such, have the physico-chemical properties that allow them to cross the stratum corneum of the skin. They can only cause their response as part of a complete antigen, involving their association with epidermal proteins forming hapten-protein conjugates. This, in turn, requires them to be protein-reactive.

The conjugate formed is then recognized as a foreign body by the Langerhans cells (LCs) (and in some cases other Dendritic cells (DCs)), which then internalize the protein; transport it via the lymphatic system to the regional lymph nodes; and present the antigen to T-lymphocytes. This process is controlled by cytokines and chemokines - with tumor necrosis factor alpha (TNF-α) and certain members of the interleukin family (1, 13 and 18) - and their action serves either to promote or to inhibit the mobilization and migration of these LCs. (Kimble et al. 2002) As the LCs are transported to the lymph nodes, they become differentiated and transform into DCs, which are immunostimulatory in nature.

Once within the lymph glands, the differentiated DCs present the allergenic epitope associated with the allergen to T lymphocytes. These T cells then divide and differentiate, clonally multiplying so that if the allergen is experienced again by the individual, these T cells will respond more quickly and more aggressively.

White et al. have suggested that there appears to be a threshold to the mechanisms of allergic sensitisation by ACD-associated allergens (1986). This is thought to be linked to the level at which the toxin induces the up-regulation of the required mandatory cytokines and chemokines. It has also been proposed that the vehicle in which the allergen reaches the skin could take some responsibility in the sensitisation of the epidermis by both assisting the percutaneous penetration and causing some form of trauma and mobilization of cytokines itself.