Anti-IL-17 a New Treatment for Contact Dermatititis

Purpose The purpose of this study is to assess the efficacy of anti-IL 17 treatment (secukinumab) in patients with known severe allergic contact dermatitis (ACD).

Background ACD is an immune mediated disease characterized by itching, erythema, vesicles, thickening and scaly skin, affecting a large part of the population in the world. A review study from 2007 by Thyssen et al that summarizes studies from North Europe and North America from 1966-2007 suggests that the prevalence to at least one allergen among these populations was 21.2 % (range 12.5-40.6%)(1). The incidence of ACD is not static and differs in countries(1), but in recent years there has been an increasing incidence of ACD caused by an increasing number of environmental detergents(2, 3). For patients with severe ACD the disease can be associated with difficulties performing daily activities, loss of sleep and reduced life quality (DLQI)(4).

ACD is treated with moisturizing creams, topical steroids and in severe cases systemic steroids, UVB, PUVA, azathioprin or alitretinoin. However, the drugs have severe side effects and some patients with ACD do not respond to the already existing treatments. New treatments are therefore highly needed. A group of these patients suffer from severe eczema often resulting in impared lifestyle and not seldom loss of work(4).

The pathogenesis in ACD is a T-cell mediated delayed type hypersensitivity reaction, consisting of a sensitization and an elicitation phase (5). In the sensitization phase an exogen allergen(hapten) is entering the epidermis through a defect skin barrier. The allergen is presented by the Langerhans cells to CD4+ and CD8+ T-cells in the lymphatic nodes, which activates and increases the numbers of T-cells. The elicitations phase begins when the patient once again is in contact with the allergen. The T-cells react with the allergen and this releases cytokines such as IFN-ɣ followed by skin lesions and inflammation. The IFN-ɣ is an important inflammatory cytokine, which is produced by CD4+ and CD8+ T-cells during ACD in humans and mice(6, 7). However, in the last decades studies have revealed that other inflammatory cytokines, such as IL-17 and IL-22 may be of importance in the immune response to contact allergens(8-11). IL-17 is produced by T-helper (TH)17 cells, innate cells as macrophages and dendrit cells and other cell types(12).

In mice both CD4+ and CD8+ T-cells producing IL-17 have been identified(13). A study by Nakae et al where IL-17 deficient mice were generated and exposed to dinitroflorobenzene and trinitrochlorobenzene, the mutants had a markedly reduced ear swelling compared to wild-type mice, this suggesting that IL-17 plays a role in contact allergy (14).