The mechanisms of action of phototherapy in the treatment of the most common dermatoses

Abstract

Phototherapy denotes the use of ultraviolet (UV) light in the management of several dermatoses. Most phototherapy regimens utilize ultraviolet radiation of different wavelenghts. Currently, irradiations with broadband UVB (290-320 nm), narrowband UVB (311-313 nm), 308 nm excimer laser, UVA 1 (340-400 nm), UVA with psoralen (PUVA), and extracorporeal photochemotherapy (photopheresis) are being used. The interplay of the various photobiologic pathways is far from being completely understood. Disordes that may benefit from such approach are numerous, with psoriasis, atopic dermatitis, cutaneous T-cell lymphomas, morphea, and vitiligo as main indications. The immunomodulatory effects of UVB radiation primarily affect the epidermis and superficial dermis, while UVA radiation affects mid and deep dermal components, especially blood vessels. UVB radiation is absorbed by endogenous chromophores, such as nuclear DNA, which initiates a cascade of events. Absorption of UV light by nucleotides causes the formation of DNA photoproducts and suppresses DNA synthesis. In addition UV light stimulates synthesis of prostaglandins and cytokines that play important roles in immune suppression. It may reduce the number of Langerhans cells, cutaneous T lymphocytes and mast cells in the dermis. UV radiation can also affect extranuclear molecular targets located in the cytoplasm and cell membrane. Immune suppression, alteration in cytokine expression, and cell cycle arrest may all contribute to the suppression of disease activity. PUVA is a form of chemophototherapy which uses UVA light to activate chemicals known as psoralens, hence psoralen ultraviolet A. The conjunction of psoralens with epidermal DNA inhibits DNA replication and causes cell cycle arrest. Psoralen photosensitization also causes an alteration in the expression of cytokines and cytokine receptors. Psoralens interact with RNA, proteins and other cellular components and indirectly modify proteins and lipids via singlet oxygen-mediated reactions or by generating of free radicals. Infiltrating lymphocytes are strongly suppressed by PUVA, with variable effects on different T-cell subsets. Psoralens and UV radiation also stimulate melanogenesis. Extracorporeal photopheresis is technique used in treatment of erythrodermic cutaneous lymphomas. It is very potent in induction of lymphocyte apoptosis. Despite the introduction of numerous effective systemic medications and biologic agents in dermatology, phototherapy remains a reliable, and often preferred option for several dermatoses.