Early Reacting Tissues: Skin

Abstract

1. Skin consists of an early reacting epidermis (with appendages) and late — reacting dermal connective tissue. 2. The Epidermis: Early Reactions: (a) The basal layer includes: [i] radiosensitive true stem-cells (10%) and [ii] a larger number of radioresistant transit cells which after 1–3 divisions move into the suprabasal layers and differentiate into prickle, granular and cornified cells and are eventually shed. (b) The radiosensitive stemcells are the target cell for early reactions. Their death stops the influx of transit cells which continue to divide and differentiate at the same preirradiation rate until the limited division potential is exhausted when epidermal depletion occurs. (c) Clinically, transient erythema occurs within 24 h followed by a latent period of 8-10 days and then a sequence of reactions that can be graded as: mild erythema, brisk erythema, wet desquamation and necrosis. (d) Repopulation starts after 2-4 weeks with formation of microcolonies which, enlarge into visible macrocolonies and both may be used to measure stem-cell survival. Regeneration occurs from surviving stem-cells within: [i] the irradiated area, [ii] hair follicles and sebaceous glands, and [iii] the boundary unirradiated zone. (e) For areas <10 cm, healing is better in smaller areas (contribution of the boundary zone), but this does not apply to larger areas. Clinically the same degree of a reaction may be acceptable if implicating a limited area but unacceptable in larger areas. (f) UV light indiscriminately kills stem and transit cells. Hence the latency is shorter and the evolution of reactions quicker. 3. Skin Appendages: (a) The stem-cells in the germinal matrix of hair follicles and the nail root and the basal epithelium of sebaceous and sweat glands are responsible for growth. (b) Within 1–3 days after irradiation death of germinal cells results in hair dysplasia (short thin hair). The proportion of dysplastic hair is dose-dependent and may be used to score damage. Epilation occurs during the third week and regrowth may occur after 1-3 months (c) Sebaceous glands are as sensitive as hair but sweat glands are less radiosensitive. Regenerated skin may be dry and hairless. 4. The Dennis: Late Reactions: (a) Fibroblasts and vascular endothelial cells (the target cells of late effects) are slowly proliferating but become active after injury. (b) Dermal fibrosis, telangiectasis and late dermal necrosis are the main late effects. They develop slowly for several years. (c) Surgical trauma following preoperative irradiation may precipitate death of target cells when they attempt to divide. Postoperative irradiation may also suppress their proliferation and delay wound healing. 5. Non-Epidermal Elements: (a) Melanoblasts are slowly dividing. Their injury leads to depigmentation as a late effect. But hyperpigmentation may occur near the boundary zone. (b) Langerhans cells belong to the lymphoid immune system and serve a surveillance function. 6. Dose-Time Factors for Early and Late Damage: (a) Early and late effects are unrelated (different target cells). (b) Repopulation of epidermal cells occurs during conventional daily fractionation. Hence, prolongation of the overall time reduces acute reactions. However, no detectable proliferation of dermal elements takes place within about 60 days and hence late effects are independent of the treatment time. (c) Due to a better repair capacity (low a/), late reactions are more dependent on the fraction size than early effects.