Current concepts in contact dermatitis

Two important concepts that improve our understanding of the mechanisms involved in allergic contact dermatitis have been reviewed recently.1,2 They help explain why allergic contact dermatitis (ACD) commonly develops in patients with chronic dermatitic conditions. The two concepts are dose of allergen per unit area of skin exposed and ‘danger signals’, i.e. irritant contact dermatitis (ICD) facilitates allergic contact sensitization. Friedmann and colleagues3–7 have studied extensively the dose response of the sensitizing capacity of dinitrochlorobenzene (DNCB). It has been shown that the following factors are also important in determining whether sensitization occurs: the vehicle,8 the number and duration of exposures,9 underlying skin irritation,10,11 and occlusion.12 It is harder to sensitize atopic individuals3 because of the inherent differences in their immune systems from nonatopics. However, the dose per unit area of skin exposed is the most critical factor for any given allergen in determining sensitization.4 A weak allergen, such as lanolin,13 used over a wide area may cause sensitization compared with a strong allergen, such as epoxy resin, used over a small area. However, a strong allergen used at a low level can be used over a wide area with only a small risk of sensitization. The use of Kathon or methylchloroisothiazolone/methylisothiazolone (MCI/MI) in cosmetics and toiletries is a good example of how important the dose per unit area is in determining skin sensitization. When MCI/MI, an irritant and potent allergen, was introduced in the 1980s there followed an epidemic of ACD in the ensuing years.14 The MCI/MI story has now unfolded such that the cosmetic and toiletry manufacturing companies are able to use this biocide at acceptable levels, which produces a low level of sensitization.15 If the concentration in cosmetics and toiletries is increased the incidence of allergic contact dermatitis rises.16 Of course, the type of exposure is an important factor in determining sensitization in consumer products and exposure will be greater for leave‐on products than for rinse‐off. A product containing a strong allergen at a very low dose over a wide area will make the risk of sensitization less likely. In dermatology patients, the exposure to medicaments is greater than for cosmetics because they are applied to wide areas of the body with multiple applications per day over many months, if not years. In the case of leg ulcer patients, occlusive dressings are also applied. Patients with chronic eczematous processes have increased stratum corneum permeability and this will enhance penetration of potential allergens and again increase the exposure compared with normal skin. There are also the ‘danger signals’ from the ongoing dermatitis to consider. It is therefore no surprise that patients commonly become sensitized to products (medicaments, cosmetics and toiletries) in contact with their skin. The intrinsic properties of the allergen are important in determining whether a particular chemical is a sensitizer. Usually the allergen has a low molecular weight (< 1000),17 has the appropriate physico‐chemical properties, i.e. it is lipophilic18 and will react with proteins to form haptens or be easily metabolized from prohaptens to reactive forms.19 Concomitant inflammation will facilitate this process20 (see below). Fortunately, by and large the medicament allergens are weak sensitizers13 but the dose per unit area will be high and with many of the other determining factors being in place, medicament allergy is not an uncommon occurrence. Patch‐testing clinicians tend to use a percentage concentration of the allergen in the patch tests, i.e. the weight per volume allergen applied rather than the total amount. Friedmann and colleagues have shown that it is the total dose to the area exposed that is important.4–7 Their experimental data with DNCB has been shown to be true in the field, as the MCI/MI data demonstrates.1 The dose per unit area concept should now lead to a rethinking of the way that patch tests are dosed.