Skin and Mucosa

A biological model proposed to explain radiotherapy-induced dermal and mucosal changes identifies four phases: inflammatory, epithelial, ulcerative, and healing. During the inflammatory phase, free radicals and cytokines, such as interleukin-1β, prostaglandins, and tumor necrosis factor-α (TNF-α), are released in response to irradiation. These inflammatory mediators increase vascular permeability and contribute to tissue damage.¹³

In the epithelial phase, cellular reproduction declines, leading to desquamative pseudomembranous degeneration. The ulcerative phase marks the period when ulcerated tissue is most painful and highly vulnerable to infection. Additionally, an increase in gram-negative bacteria may further amplify the inflammatory response. The final healing phase begins when epithelial regeneration restores tissue integrity.¹³

Radiodermatitis and oral mucositis arise due to the depletion of the basal cell layer, which is responsible for rapid epithelial renewal. Skin reactions to radiotherapy occur in approximately 25% of patients and depend on the radiation dose and the volume of tissue exposed. With conventional dosing, these reactions typically appear within the first three weeks of treatment and may manifest as erythematous, desquamative, or necrotic lesions.¹³

Radiotherapy-induced mucositis primarily affects non-keratinized tissues, including the labial and buccal mucosa, soft palate, pharynx, floor of the mouth, and tongue. It is characterized by edema and erythema, followed by desquamation. As desquamative lesions advance, they develop into painful ulcerations, which may become colonized by Candida species, ultimately leading to acute or chronic candidiasis (Figure 6).¹³

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

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.

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.

Figure 8.

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