Contact allergy (overview) L23.9

Antigen-specific, T-cell-mediated, delayed type IV immune reaction (Gell and Coombs) that can occur after repeated exposure to contact allergens (see also Allergy, type IV reaction) in appropriately predisposed individuals. The predisposition may be based on genetic or non-genetic factors (see contact allergy, genetics). Other non-specific factors such as infections may also be involved in the initiation of the contact allergic reaction.

The most common contact allergens are metal allergens(nickel) followed by cosmetics, creams, sunscreens, and topically applied medications. Typical for a contact allergic reaction are scatter reactions, which can often occur in the immediate vicinity of the contact site but also far away as a systemic scatter reaction.

Rarer are so-called contact allergies of the immediate type (detection by atopy patch test), a type IV reaction triggered by type I allergens - here the most common triggers are plant and animal products.

Remarkably, a lower frequency of contact allergies is detectable in psoriatic patients (Claßen et al.2017).

Allergic contact dermatitis (contact eczema) is the prototype of a cell-mediated immune reaction of the late type (DTH = delayed-type hypersensitivity, type IV reaction according to Coobms and Gell). Basically, according to our ideas, this reaction proceeds in 2 phases:

Sensitization phase:

• In the sensitization phase, keratinocytes and dermal mast cells are stimulated to produce large amounts of interleukin-1 and TNF-alpha shortly after application. These are responsible for the maturation of Langerhans cells into immunostimulating dendritic cells (DCs). Antigen-loaded dermal dendritic cells (DDCs) enter the draining lymph nodes. There, they present the MHC antigen complex to naïve T cells (see antigen presentation below) that carry the T cell receptor matching the antigen (or hapten protein complex). This triggers a Th1/Tc1 and Th17/Tc17-predominant T cell response.
• Haptens activate the ERK1/2 mitogen-activated protein kinase (see MAP kinase signaling pathway below) in human dendritic cells by binding to thiol groups. Similarly, they induce enhanced expression of interleukin 1-beta mRNA. Hapten-activated keratinocytes express more TNF-alfa, IL-1ß, GM-CSF, chemokines, adhesion molecules (LFA-1 and ICAM-1 see below Integrins).
  • Langerhans cells activate the T cell interaction of the MHC I (major histocompatibility complex) or MHC II presenting hapten with the hapten-specific T cell receptor.
  • Alternatively, activation occurs via costimulatory molecules, e.g. B7-1, B7-2, ICAM-1. Both signals together lead to activation and clonal expansion of hapten-specific CD4 and CD8 cells, which are able to migrate into the skin by their pattern of adhesion molecules and chemokine receptors (specific homing).

Secondary antigen contact (trigger phase):

• Re-contact with the same allergen leads to activation of antigen-specific memory cells. These develop into effector cells that initiate an inflammatory reaction (clinical: erythema, edema, itching, vesiculation, scaling; immunological: cytokine release, recruitment of further inflammatory cells). Immunological process: Specific memory T cells, which are activated after renewed contact with the antigen and transform into effector cells, are initiators of the inflammatory reaction, but not its executors. CD4+ and CD8+ T cells are mainly involved in the triggering phase of AKD. The number of CD8 T cells increases in the skin 6-18 hours after contact with the hapten and is accompanied by an increase in IFN-gamma. Nonspecific inflammatory cells (e.g. neutrophil granulocytes, mast cells, macrophages) act as executors.
• New contact with haptens leads directly and concentration-dependently to:
  • Increased expression of surface molecules and production of cytokines by epidermal cells as well as endothelia. In this process, a certain non-specific irritative activity of the hapten is a prerequisite for the triggering of an allergic contact allergy.
  • Recruitment of antigen-specific T cells to the site of Ag contact by inflammatory signals to release chemokines and cytokines from keratinocytes.
  • Activation of endothelial cells, as presentation of antigen to T cells can only occur extravascularly, and expression of adhesion molecules, e.g. E-, L-, P-selectin; ICAM-1, LFA-1, CD18.

Cutaneous inflammatory response:

• After hapten-specific activation, cytotoxic T lymphocytes (CTL) lyse the hapten-modified (and thus attackable) keratinocytes. This results in the release of inflammatory mediators, recruitment of mononuclear cells, and amplification of the immune response. In addition, both TH1 and TH2 cells produce cytokines and mediators (e.g. INF gamma, TNF-alpha, IL-12), which also lead to an amplification of the response locally. Substance P and CGR peptides (calcitonin gene related peptide) also act in terms of an enhanced inflammatory response. This is in contrast to the effects of IL-4 and IL-10, which are produced by CD4+ TH2 cells and are involved in a negative regulation of AKD. This also applies to some neuropeptides, such as alpha-MSH and the vasoactive intestinal peptide (VIP).
  • Antigen-specific T cells can stimulate resident mast cells to produce TNF-alpha as well as MIP-2/IL-8. TNF-alpha induces expression of adhesion molecules that enable neutrophil granulocytes to bind to vascular endothelia. MIP-2/IL-8 establishes a chemotactic gradient responsible for transvascular diapedesis and pinpoint migration to the tissue locus contacted by haptens.

Contact allergy is a common disease. 15-20% of the general population is sensitized to one of the common contact allergens. Manifestly about 8% of adults and 5-6% of children get sick once in a lifetime. Sex-specific differences are not found.

Recent data on the frequency of allergic diseases in children show 12-month prevalence data for allergic rhinitis of 9.1%, atopic eczema of 6.0%, and bronchial asthma of 4.1% (Worm M et al).

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