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Basic mechanisms and pathophysiology of allergic contact dermatitis

Anthony Gaspari, MD
Section Editor
Joseph Fowler, MD
Deputy Editor
Rosamaria Corona, MD, DSc


Allergic contact dermatitis (ACD) is a common inflammatory skin disease presenting with pruritic, eczematous lesions. ACD results from a T cell-mediated, delayed type hypersensitivity (DTH) reaction elicited by the contact of the skin with the offending chemical in individuals who have been previously sensitized to the same chemical. ACD is common in the general population and is the most frequent occupational skin disease. Its etiology may be suggested by the body sites of involvement, history of exposure, and morphology and distribution of the skin lesions.

This topic will discuss the immune mechanisms and pathophysiology of ACD. The clinical manifestations, diagnosis, and management of ACD are discussed separately. (See "Clinical features and diagnosis of allergic contact dermatitis" and "Management of allergic contact dermatitis".)


The understanding of the cellular and molecular pathogenesis of allergic contact dermatitis (ACD) has expanded dramatically. In addition to CD4+ and CD8+ T cells, other cell types such as natural killer T (NKT) cells and T regulatory cells have emerged as critical participants (table 1). In the elicitation phase, Langerhans cells appear to play a role in the development of immune tolerance rather than hypersensitivity reaction (as was once thought). B cells also appear to be important during the initiation of ACD by secreting IgM antibody in response to NKT cell-derived interleukin (IL)-4, leading to complement activation and immune cell chemotaxis. As new mechanisms and molecules emerge as a result of advances in the understanding of ACD, new pharmacologic targets will become apparent.


Hapten binding is the initial step in the development of allergic contact dermatitis (ACD). Contact allergens are low molecular weight (<500 Daltons) chemicals called haptens, which are able to penetrate the stratum corneum barrier of the skin. Haptens are not immunogenic by themselves, but they can be efficiently recognized by the immune system after binding to a skin protein carrier. Haptens may be naturally occurring substances such as urushiol found in the resin of poison ivy, synthetic compounds, dyes, fragrances, drugs, or heavy metal salts.

The binding of haptens to skin proteins (protein haptenation) involves the formation of a covalent bond between the electrophilic components of the hapten and the amino acid nucleophilic side chains of the target proteins within the skin [1]. Examples of chemicals containing electrophilic components are aldehydes, ketones, amides, or halogenated compounds. Metal cations (eg, nickel [NIi]2+, one of the most common ACD-associated haptens; and chromium [Cr]3+) are also well-known electrophiles. Some haptens that are not normally electrophilic (prohaptens) can be converted to protein-reactive species via oxidation or metabolic transformation by epidermal keratinocytes and/or dendritic cells [1]. Additional factors influencing the sensitizing ability of haptens include lipophilicity, tridimensional chemical structure, and protein-binding affinity.


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Literature review current through: Sep 2016. | This topic last updated: May 19, 2015.
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