Allergic contact dermatitis: novel mechanisms and therapeutic perspectives

Allergic contact dermatitis is a common eczematous skin disease that occurs in sensitized individuals at the site of contact with small chemicals penetrating the skin barrier. The onset of the disease is mostly due to the rapid recruitment of chemical-specific CD8+ T cells, which induce apoptosis of keratinocytes. Additionally, CD4+ Th1 and Th17 contribute to the extension of the inflammatory reaction by releasing pro-inflammatory cytokines that activate keratinocytes and other skin resident cells. The immune reaction is tightly regulated through multiple mechanisms. In particular, T cell population with regulatory function, such as T regulatory cells 1 and CD4+CD25+ T regulatory cells have a critical role in preventing the development of allergic reactions to innocuous chemicals contacting the skin, and in limiting the magnitude of the inflammatory process in already sensitized individuals. Allergic contact dermatitis is a chronic disease, which lasts, in most cases, for the entire life of the affected individual. Thus, prevention and avoidance of contact with the sensitizer are critical factors in the management of affected patients. The gold standard therapeutic approach for the disease remains the local and/or systemic immunosuppression, aimed to block T cell functions and keratinocyte responsiveness to pro-inflammatory stimuli. However, alternative approaches that aim at preventing T cell accumulation in peripheral tissues are under investigation. Most recently, disclosure of mechanisms regulating allergic contact dermatitis have provided new therapeutic perspectives for the disease, mostly based on immunomodulatory interventions, as in the case of induction of specific oral tolerance to the causative allergen.