Radiation dermatitis, also known as Radiodermatitis or radiation burns, are the cutaneous and subcutaneous manifestations of the effects of ionizing radiations as a result of radiation therapy, with or without chemotherapy. The common sources of radio waves include ionizing radiation, ultraviolet radiation, thermal radiation and radiofrequency energy among others. Patients exposed to X-rays and fluoroscopic techniques during routine medical examinations are also at an increased risk of developing radiation dermatitis. Cavity magnetrons, which emit microwaves, when not used properly, pose a threat of radiation induced skin damage as well. Radio frequency waves above the allowed limits tend to become resonant (frequencies ranging from 80MHz to 1GHz), which pose a threat of radiation dermatitis as well. Microwaves are also capable of causing radiation burns in rare cases. Radioactive fallouts and nuclear explosions (in factories and laboratories) also cause a significant amount of damage due to radiation burns.

The radio waves react with the superficial layers of the skin, sometimes penetrating deeper to the tissue and cellular levels leading to DNA damage. Prolonged exposure to these waves leaves little time for the cell cycle to repopulate the damaged areas, which could lead to severe damage and necrosis. The most common reaction in response to these radio waves is erythema (redness of the skin), which, depending on the severity of the radiation, is followed by dry desquamation, or moist desquamation (removal / shedding of the upper and outermost layer of the skin), that may or may not lead to ulceration and ultimately necrosis.

The basic pathophysiology of radiodermatitis involves a combination of radiation induced skin injury and a consequent inflammatory response at the entry and exit site of the rays. These radio waves destroy the mitotic divisibility of the stem cells under the basal layer of the skin (the deepest of the five layers of the epidermis, the outermost covering of the skin in mammals, known as stratum basale), which stops their growth and repopulation and hampers the integrity of the skin.

Radiation induced skin damage manifests within 1 to 4 weeks of the start of the therapy and continues for weeks to months, and if not taken care of properly, may prolong for years. The latter is applicable mostly to health professionals, radiologists, and vascular interventionalists, who are constantly exposed to radiation and are hence at the greatest risk of developing the most severe form of the condition.

Radiation dermatitis is mostly accompanied by prolonged pain and discomfort surrounding the affected areas. Patients with such a condition are more prone to development of radiation induced cancers like squamous and basal cell carcinoma.

Resolution of the acute phase of radiation dermatitis sometimes leads to a passive condition called radiation acne, which resemble papules at the affected sites. Another allergic reaction, called radiation recall reaction, occurs when a chemotherapeutic agent is administered at a previously irradiated site. Restated radiation dermatitis refers to inflammation of previously irradiated parts of the skin, depending on the severity of the same.

Management of patients with radiation dermatitis depends mostly on checking and controlling the dosage of radiation along with any accessory chemotherapeutic agents that might be necessary for treatment, as most patients of radiation dermatitis are patients of squamous cell carcinoma of the head and neck. Another factor which is to be noted in the management of this condition is the site of radiation. Surfaces that are radiosensitive (eg: the breast tissues), or places that require high intensity beams for optimum effect (like places with folds in skin) should be avoided. Suitable supportive therapy should be employed to take care of the affected areas and prevent them from secondary infections.

Etiology:

Radiation dermatitis occurs in 95% of the cases where people receive radiotherapy, with or without chemotherapy. For most cases, the consequences are mild to moderate, but around 20 to 25% of the patients face severe consequences, depending on the intensity, duration, angle of incidence and fractionation (fraction of dosage spread over time), area of skin exposed and machine defects among others.

Hyper fractionation (a condition where small doses of radiation are administered a number of times in a day, at least twice, for maximum effect) and altered fractionation with parallel boost of dosage (increasing the fractionated dosage gradually for optimum results) often result in severe conditions like ulceration and necrosis. The normal dosage for people with epithelial tumors ranges from 60 to 80Gy, and for people with lymphomas, the dosage ranges between 20 to 40Gy, with fractionated dosage being 1.8 to 2Gy in strength. However, when this is altered and increased to beyond 20Gy, which is the maximum limit for fractionated dosage strength in adults with severe forms of cancer (total dosage exceeding 60Gy), with these patients needing parallel chemotherapeutic boosters, there is an increased risk of severe radiation dermatitis.

The various risk factors for patients developing radiation dermatitis can be summarized as follows,

• Nutritional deficiencies and developmental problems in patients lead to deformities in skin and make them more prone to radiation induced injuries than their healthy counterparts. Nutritional deficiencies also alter wound healing capabilities of an individual, which slows down recovery as well.
• Sensitivity of skin to radiation (mostly neck, extremities, chest, abdomen, face, hair scalp, breast tissue) and implants and reconstructions also affect the severity of the condition.
• Types of radiation, depending on photons and electrons, have different impacts on the skin. Electrons penetrate less as compared to photons, and have to be administered in high doses, whereas photons penetrate deeper and release energy. Both can have adverse consequences. Hence, continuing a moderate dosage is advisable. Intensity Modulated Radiation Therapy (IMRT) has been shown to lower risks of radiation burns.
• The volume of tissue treated also matters, as it affects the intensity and duration of dosage.
• Chemotherapeutic agents like Doxorubicin, Bleomycin, 5-Fluorocil, etc., can cause severe damage to skin when combined with increased dosage of radiation.
• Existing co-morbidities like anemia, diabetes and immunosuppression (eg: HIV), genetic disorders, connective tissue disorders (eg: lupus, scleroderma, and mixed connective tissue disorder), also contribute to the severity of the condition.
• Old age worsens the repair process needed to combat the vasculo-connective and epidermal damages rendered as a result of radiations.
• Smoking and tobacco usage reduces the oxygen carrying ability of blood, increasing the amount of carbon dioxide in it, which can cause a reduction in macrophage activity, induce platelet stickiness and reduce epithelialization (ability of skin cells and vasculature to grow and regenerate themselves).
• Obesity is another noted risk factor simply because of the fact that a larger surface area is exposed to these rays and hence poses more threat than their non-obese counterparts.

Pathophysiology:

Radiation causes skin irritation, which marks the inception of a complex pattern of tissue injury and inflammatory cell recruitment. Initially, the epidermal and the dermal vasculature are affected, and subsequent damage takes place among the keratinocytes (most abundant type of skin cells found in the epidermal layer). The keratinocyte DNA gets damaged, occasionally irreversibly, which makes it difficult for these cells to undergo the full cell cycle, making repopulation and repair of skin inconvenient and burdensome. Cell death normally occurs after 1 to 5 cycles of radiation therapy.

The p53 pathway, a tumor suppressor pathway, which is pivotal in controlling the replicating cells aiding in the regulation of cell cycle, replication of DNA and induction of apoptosis (programmed cell death) is found to be faltered in radiation affected individuals. It is believed that the activity of the p53 protein, crucial for the cell cycle to progress through its various checkpoints, is hampered by the DNA damage caused due to radiation. This further leads to activation of p21, a protein that contributes to prevention of segregation of the sister chromatids into daughter chromosomes along the spindle fibers of the mitotic apparatus. This hinders the growth and repopulation of keratinocytes and leads to skin damage.

Hydrolysis of water inside cells, leading to formation of free radicals, is another contributor to acute radiation dermatitis. Secretion of pro-inflammatory cytokines (Interleukins 1 and 6, Transforming growth factor β and Tumor Necrosis Factor among others), increased secretion of Epidermal Growth Factor Receptor (EGFR) to replenish for the loss of keratinocytes, and increased neutrophilic secretions in severe cases, form the inflammatory make-up of radiation dermatitis.

The nature of radiation also plays a major part in determining the severity of the condition. Beta (β) rays are the ‘safest’ when it comes to assessing the fate of radiation dermatitis in patients. They are shallow in terms of penetration and mostly get manifested within the epidermis and dermis, within 24-48 hours of exposure. Erythema and irregular skin pigmentation accompanied by dry desquamation marks the most common symptoms in this case. However, severe burns can cause wet desquamation and ulceration, leading to necrotizing dermatitis. This is very rare.

Gamma (γ) rays, on the other hand, penetrate deeper into the skin and have more severe effects, ultimately leading to a more chronic form of the condition which remains underlying in most cases, without surfacing till the very end.

There are two forms of the condition – the acute phase and the chronic phase.

The acute phase refers to the immediate manifestation of erythema with or without desquamation, within 24 hours of irradiation, with various grades of severity, all visible within 30 days of exposure. Doses in excess of 2Gy, extending as much as 24Gy (the most severe of them, leading to ulceration and necrosis) are capable of causing such conditions, resulting mainly from structural tissue damage and irreversible breakage of cellular DNA. This can last up to weeks after irradiation but ultimately resolve in most cases, unless very severe. Hyperemia and epilation, followed by dry desquamation are common features within a few weeks (when dosage exceeds 6Gy) and for doses from 7 to 17Gy and above, moist desquamation and ischemic dermal necrosis are observed.

The chronic phase refers to a more prolonged ‘sub-cutaneous’ phase of the condition where rays penetrating deeper into the epidermis and dermis due to prolonged exposure to radiation, cause dermatitis of varying severity, mostly characterized by dry and hard patches of skin (plaques), mostly wheatish or whitish in nature, disappearance of follicular structures, increase in collagen and damage to elastic fibers of the dermis, with telangiectasia (appearance of prominently dilated blood vessels near the surface of the affected area) and occasionally with hyperkeratosis (a condition referring to the thickening of the outer layer of epidermis). It is more commonly an occupational hazard with more healthcare professionals involved in radiologic processes getting affected in the longer run due to prolonged exposure in dealing with patients.

 

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