Photodermatoses and Skin Cancer

Abstract

Photodermatoses are a group of skin diseases caused or exacerbated by light. Their classification is traditionally based on the cause of the disorder and on the pathology of cutaneous response. Polymorphic light eruption (PLE) is the commonest photosensitive disorder affecting up to 20% of the population, characterized by an intermittent eruption of non scarring pruritic erythematous papules, vesicles or plaques that develop on ultraviolet (UV) radiation (UVR)-exposed skin (Stratigos et al., 2002). The course of the disease is mainly chronic. The disease is multifactorial: a genetic susceptibility has been identified as well as environmental components. The spectrum of radiation that induces PLE is most commonly UVA and/or UVB wavelengths and, rarely, visible light. Epstein first hypothesized, over 60 years ago, that PLE was an immune-mediated disease. He postulated that PLE was a delayed-type hypersensitivity reaction (DTHR) to UVR induced cutaneous antigens (Epstein, 1986). Only during the past 20 years have studies emerged that support this theory. It is hypothesized that the DTHR associated with PLE is secondary to a partial failure of UVR-induced immunosuppression in patients with PLE. Multiple studies highlighted the greater role of Langerhans cells (LCs) in the sensitization phase and therefore suggested that LC dysfunction may be the underlying cause of PLE. In fact, in patients with PLE, LCs persist in the epidermis after intermittent UVB exposure whereas, in normal subjects, LCs disappear from the epidermis. In contrast, neutrophil infiltration in the skin after UVB exposure is significantly decreased in patients with PLE. Less neutrophilic infiltration may lead to impaired local production of cytokines such as interleukin (IL)-4 and IL-10. Altering the local skin milieu after UVR exposure eventually leads to activation of the skin immune response instead of suppression (Cooper et al., 1992). These observations would lead one to suppose that failure of immunosuppression following UVR exposure might give an advantage with regard to recognition of UV-induced tumour antigens and more effective elimination of such antigenic cells by the immune system. UVR-induced skin cancer (SC) is the most prevalent form of human neoplasm. It is well known that UVB (280– 320 nm) and UVA (320-400 nm) radiation can induce DNA damage leading to melanoma or non melanoma SC by provoking mutations and immunosuppressive effects. The molecular changes induced by UV generate multiple consequent or concomitant mechanisms: DNA damage with thymidine dimer formation, urocanic acid (UCA) isomerization from transUCA to cis-UCA, depletion of some protective cytokines such as IL-1, IL-12 and interferon-γ (IFN-γ), or the increase of tumour necrosis factor-α (TNF-α), IL-6, IL-10 and IL-15, resulting