Skin and Mucosa

A biological model proposed to address the changes associated with radiotherapy-induced dermal and mucosal changes suggests an inflammatory, epithelial, ulcerative, and healing phase. During the inflammatory phase, free radicals and cytokines, e.g., interleukin-1β, prostaglandins, and tumor necrosis factor-α (TNF-α), are released in response to irradiation. These chemical mediators of inflammation increase vascular permeability and cause tissue damage.¹³

During the epithelial phase, cellular reproduction reduces, which leads to desquamative pseudomembranous degeneration. The ulcerative phase heralds the period when the ulcerated tissue is most painful and susceptible to infection. In addition, the number of gram-negative bacteria may increase, further stimulating the inflammatory process. The final or healing phase occurs when epithelial regeneration can reestablish tissue integrity.¹³

Radiodermatitis and oral mucositis develop secondary to the depletion of the epithelium's rapidly dividing basal cell layer. Skin reactions to radiotherapy are estimated to affect about 25% of patients and depend on the dose delivered and the tissue volume irradiated. Skin reactions appear within the first three weeks of radiotherapy with conventional doses. These reactions may be erythematous, desquamative, or necrotic.¹³

Radiotherapy-induced mucositis generally appears on non-keratinized tissues such as the labial and buccal mucosa, soft palate, pharynx, the floor of the mouth, and the tongue. It is associated with edema and erythema of the affected tissues, followed by desquamation. Desquamative lesions progress to painful ulcerations and may become colonized by Candida organisms. The progression will result in acute or chronic candidiasis. (Figure 6).¹³

Figure 6. Acute radiotherapy-induced mucositis and candida infection.

During conventional radiotherapy protocols (i.e., 2 Gy/day, 5 days/week, for 5–7 weeks), cellular repopulation of the epithelium can counteract the destructive effects of radiotherapy dosing of up to 1.8 Gy/day is unlikely. After the first week of therapy, there will be hyperemia and epithelial atrophy followed by edema and erythema due to hyperemia. Painful desquamative pseudomembranous lesions and ulcerations mark the second and third weeks of therapy (Figure 7).¹³

Figure 7.

Acute radiotherapy-induced ulceration during the 2nd and 3rd week of therapy, also note the thick, viscous and frothy character of saliva.

Pharyngeal mucositis may impair the patient’s ability to swallow and speak. An estimated 60% of patients undergoing conventional radiotherapy for head and neck cancer develop severe mucositis and require pain control and nutritional supplementation. With more intense radiotherapy, the incidence of mucositis may exceed 90%. However, complete healing in most patients occurs within four weeks after the completion of radiotherapy.¹³

Long-term effects associated with irradiated oral mucosa include tissue atrophy, telangiectasias, and increased risk of chronic ulceration (Figure 8). Cytokines and late-responding endothelial cells in the connective tissue underlie progressive fibrosis and thrombosis of small vessels in the dermis and submucosa. Radiodermatitis may result in hyperpigmentation, permanent loss of hair, and increased risk of skin cancers, typically basal cell carcinomas.¹³

Figure 8.

Long-term effects associated with irradiated oral mucosa include tissues atrophy and telangiectasias.

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