Dermal atrophy, manifesting as skin contraction, telangiectasia, and necrosis may be considered a consequence of decreased vascularization with loss of endothelial cells and reduction in capillary network. For the same reason the wound-healing ability may be severely compromised, which is of considerable clinical importance in the surgical field.

The pathogenesis of damage in irradiated tissue is not completely clear, but it is known that it primarily involves the cell as target and water, as a major constituent of the cell, plays a basic role in these events. The ionization of a molecule of water produces ROS (H+ and OH−) that have short lives and are very reactive [3]. Nowadays it is believed that indirect action of ROS in the context of tissues is the most important cause of injury than the direct action of ionizing radiation (e.g., on chromosomes). This action on the DNA causes tissue injury with endothelial cell damage resulting in inflammatory response, fibrin accumulation in extracellular matrix, and macrophage activation. The activated macrophages release several cytokines and ROS that perpetuate tissue damage. All these mechanisms contribute to the development of tissue ischemia which further stimulates production of ROS and cytokines [4].

Several groups have demonstrated that cytokines that are more prevalent in irradiated tissue are fibrogenic and proangiogenetic factors. In particular IL1 and TGF-β/Smad3 pathways have been implicated as mediators of fibrosis, and angiogenesis is stimulated via vascular endothelial growth factor (VEGF) production. Moreover to respond to proliferation induced by VEGF, endothelial cells die because of the accumulated radiation damage [5].

These changes are a common feature of response to a tissue injury, and inflammatory cells and activated macrophages are required to stimulate epidermal basal cells to proliferate and repair the damage. Conversely irradiated tissues show an intrinsic alteration in local stem cells that follow the principle of Bergonié and Tribondeau, previously described, and that is related to poor wound healing specific of radiodermatitis.