Skin and Mucosa

A biological model proposed to address the changes associated with radiotherapy-induced dermal and mucosal changes suggests an inflammatory, an epithelial, an ulcerative, and a healing phase.13 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

The epithelial phase is characterized by reduced cellular reproduction leading to desquamative pseudomembraneous degeneration. The ulcerative phase heralds the period in which the ulcerated tissue is most painful and susceptible to infection. The number of gram-negative bacteria may increase, further stimulating the inflammatory process.13 The final or healing phase occurs when epithelial regeneration is able to reestablish tissue integrity.13

Radiodermatitis and oral mucositis develop secondary to the depletion of the rapidly dividing basal cell layer of the epithelium.13 Skin reactions to radiotherapy are estimated to affect about 25% of patients and depend on the dose delivered and the volume of the tissue irradiated. With conventional dosing, skin reactions typically appear within the first 3 weeks of radiotherapy and, depending on severity, 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, floor of the mouth, and the tongue.13 It is associated with edema and erythema of the affected tissues followed by desquamation and, as a function of the absorbed dose, desquamative lesions progress to painful ulcerations, which may become colonized by Candida organisms and lead to acute or chronic candidiasis (Figure 6).13

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

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

Figure 7.
Acute radiotherapy-induced ulceration
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.13 An estimated 60% of patients undergoing conventional radiotherapy for head and neck cancer develop severe mucositis and require pain control and nutritional supplementation.13 With more intense radiotherapy the incidence of mucositis may exceed 90%.13 Complete healing in most patients occurs within four weeks after the completion of radiotherapy.13

Long-term effects associated with irradiated oral mucosa include tissues atrophy, telangiectasias, and increased risk of chronic ulceration (Figure 8).13 Cytokines and late-responding endothelial cells in the connective tissue underlie progressive fibrosis and thrombosis of small vessels in both the dermis and submucosa.13 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
Long-term effects associated with irradiated oral mucosa include tissues atrophy and telangiectasias.
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