What is the mechanism leading to allergic contact dermatitis (ACD), a type of hypersensitivity reaction?

From the Guidelines

Allergic contact dermatitis occurs through a complex immunological process involving the binding of haptens to epidermal carrier proteins, sensitization, and subsequent inflammatory reaction upon re-exposure, as described in the guidelines of care for the management of atopic dermatitis 1. The mechanism of allergic contact dermatitis can be broken down into several key events:

• The initial penetration of the skin by a hapten, a small allergenic molecule, which then binds to proteins, creating a complete antigen.
• The processing of these modified proteins by Langerhans cells and dendritic cells, which migrate to regional lymph nodes where they present the antigen to T lymphocytes, triggering the proliferation of memory T cells specific to that allergen.
• The establishment of immunological memory, allowing for a rapid response upon subsequent exposure to the same allergen.
• The recognition of the hapten by previously sensitized memory T cells upon re-exposure, activating the T cells and causing them to release pro-inflammatory cytokines.
• The recruitment of additional inflammatory cells to the site, including macrophages and more T cells, creating an inflammatory cascade.
• The resulting inflammation, which manifests clinically as erythema, vesicles, pruritus, and edema at the site of allergen contact, typically appearing 48-72 hours after exposure and representing a type IV cell-mediated immune response. The most common contact allergens include nickel, neomycin, fragrance, formaldehyde, and other preservatives, lanolin, and rubber chemicals, as identified in the study 1. Diagnosis of allergic contact dermatitis is typically made through patch testing, which involves placing suspected allergens on unaffected skin for 48 hours and assessing for a reaction, as recommended in the guidelines 1. The identification and avoidance of the suspected allergen, with subsequent resolution of the corresponding dermatitis, confirms the diagnosis of allergic contact dermatitis, highlighting the importance of a detailed history, careful evaluation, and correlation of allergy test results to determine clinical relevance 1.

From the Research

Mechanism of Allergic Contact Dermatitis

The mechanism of allergic contact dermatitis (ACD) involves a complex interaction of immune cells and the release of various cytokines and chemokines 2. The process can be broken down into several phases:

• Sensitization phase: This is the initial phase where the skin is exposed to a contact allergen, leading to the activation of antigen-presenting cells and the priming of allergen-specific T cells 2.
• Elicitation phase: This phase occurs when the skin is re-exposed to the same allergen, resulting in the activation of memory T cells and the release of pro-inflammatory cytokines 2.
• Resolution phase: This phase involves the down-regulation of the immune response and the resolution of inflammation, mediated by regulatory T cells and anti-inflammatory cytokines 2.

Key Players in the Immune Response

The immune response in ACD involves a range of immune cells, including:

• Antigen-presenting cells: These cells play a crucial role in the sensitization phase, presenting the allergen to T cells and activating them 2.
• T cells: Both CD4+ and CD8+ T cells are involved in the immune response, with CD4+ T cells playing a key role in the elicitation phase 3, 2.
• Keratinocytes: These cells are not just innocent bystanders, but are actively involved in all phases of ACD, releasing "danger" signals and interacting with immune cells 2.
• Regulatory T cells: These cells play a crucial role in regulating the immune response and preventing excessive inflammation 2.

Clinical Manifestations

The clinical manifestations of ACD can vary, but typically include:

• Localized skin rash
• Itchiness
• Redness
• Swelling
• Lesions 3, 4. In severe cases, ACD can lead to more widespread skin involvement, requiring systemic treatment with corticosteroids 4. However, in some cases, patients may develop allergic contact dermatitis to topical corticosteroids, making treatment more challenging 5, 6.