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IAEA

Erythema - general issues

» What is erythema?

Erythema means reddening of the skin due to inflammation which is usually a result of accumulation of cells of the immune system and chemicals these cells release. There can be many reasons for the occurrence of erythema: exposure to heat, insect bites, infections, allergy, non-ionizing radiation (sunlight, UV) and ionizing radiation (X-ray, nuclear radiation). Exposure of the skin to high doses of ionizing radiation leads to accumulation of lymphocytes in the layers of the skin caused by the effects of cell death and eventually to the development of erythematous skin changes. 

Erythema induced by ionizing radiation is infrequently seen in practice. General practitioners and dermatologists, who are usually the first physicians to examine patients with these skin changes, should be familiar with radiation-induced erythema and a history of a relatively recent radiological procedure is important to recognize. Patients may not be aware that the radiological procedure he/she has had can lead to erythema and therefore, may not provide a history of recent radiological procedures unless specifically asked. In some cases, the dermatologist may not recognize radiation as the cause of the skin changes and proper diagnosis may be delayed, sometimes with serious consequences for the patient.

Skin cancer as a result of radiation exposure is not a major concern but deterministic injury as described above is.

»What are the most likely sites for erythema to occur?

Radiation-induced skin injury may occur on any part of a patient’s body. Its appearance and severity depends on the circumstances surrounding the radiation event and patient specific factors such as smoking, poor nutrition, disorders of immune system (such as with cancer, or treatment of cancer or chronic infections), obesity and the presence of skin folds. Therefore, the preexisting condition of the patient and the skin prior to irradiation is of great importance. Skin that is previously compromised from previous irradiation, chemotherapy, steroid use, or surgery is more prone to radiation injury. Different parts of the skin also demonstrate different levels of sensitivity to radiation.

The skin on the anterior surface of the neck is the most sensitive region. Other sensitive body parts are (in descending order of sensitivity): flexor surfaces (the “front” of the forearms or upper arms for example) of the extremities, the trunk, the back, the extensor surfaces (“back” of the forearm or upper arm for example) of the extremities, the nape of the neck, the scalp, the palms of the hands and the soles of the feet.

» How much radiation dose to the skin is necessary to produce erythema?

Erythematous reactions depend on numerous patient specific parameters that are difficult to predict with high accuracy. For this reason, the minimum dose that might cause a skin change should not be expressed as a single threshold dose, but preferably as a threshold that includes a range of doses. Prompt skin reactions may appear within a few hours after acute exposure to radiation with a skin dose exceeding 2 gray (Gy) for the range of radiation energies encountered in X-ray machines used for interventional procedures. 

In radiation therapy a skin dose of 6 to 8 Gy with 200 kV is required for erythema to occur. Radiation of higher energies requires larger doses to produce the same degree of erythema, since in these cases the maximum dose is received in deeper tissues below the skin. In actual practice the skin dose in interventional procedures varies over the body, and it is the dose to the area with the highest skin dose (peak skin dose – PSD) that determines whether erythema will occur.

» Are some patients at greater risk for radiation injury than others?

Some rare health conditions related to defects in DNA repair genes render patients highly sensitive to radiation. Patients with the heterozygous form of the ataxia telangiectasia gene have been found to be afflicted by unanticipated serious skin injuries. Other genetically established anomalies such as Fanconi disease, Bloom syndrome, xeroderma pigmentosum, familial polyposis, Gardner syndrome, hereditary malignant melanoma and dysplastic nevus syndrome were found to be associated with increased radiation sensitivity.

Diseases such as collagen vascular diseases and diabetes mellitus are also suspected in rendering patients more susceptible to radiation induced skin injury.
The reasons why some patients with collagen vascular disease are more sensitive to radiation are unknown. Moreover, having the disease does not systematically predispose patients to heightened sensitivity. Only a few patients with collagen vascular disease have been identified as having greater radiation sensitivity.

Diabetes compromises the vascular supply and this leads to a greater risk for long-term complications. Whether or not the skin type of an individual is correlated with sensitivity for radiation induced erythema is still a matter of discussion.

» What skin effects are possible at different doses?

Skin, fat below the skin (subcutaneous fat), muscle and hair comprise the superficial tissues that are affected by radiation during medical exposures. The severity of radiation effects depends on the patient (underlying defects in DNA repair, skin integrity before irradiation, health status as noted above) and on exposure specific parameters (dose fractionation, total dose, irradiation field size). Depending on the time of appearance after irradiation, skin injuries may be classified as prompt (hours to days), early (days to weeks), midterm (weeks to months) or long term (months). Excluding patient specific factors, the severity of the injuries depends on radiation dose to the skin.

At skin doses up to approximately 2 Gy, no harmful effects are expected to be observed unless there has been prior irradiation of the skin. In the dose band of 2-5 Gy transient erythema may be a prompt reaction to radiation exposure. Epilation (hair loss) that heals in the midterm may also be observed.

Between 5 and 10 Gy epilation appears as an early reaction. For doses at the upper band limit, permanent partial epilation may be observed in the mid-term. Long term dermal atrophy or induration is also possible.

At doses between 10 and 15 Gy, dry or moist desquamation (skin loss) may develop as an early symptom. Prolonged erythema and permanent epilation in the midterm may be followed by telangiectasia (an abnormal collection of small blood vessles), dermal atrophy or induration in the long term. For doses exceeding 15 Gy, edema (skin swelling) and acute ulceration may appear as prompt reactions. Epilation and moist desquamation occur early after irradiation. In the midterm, if desquamation does not heal, a secondary ulceration may occur.

Dermal necrosis that requires surgical intervention appears at higher doses. In the long term, telangiectasia, dermal atrophy or induration and secondary skin breakdown are probable. Surgical treatment may be required if a persistent wound progresses into a deeper lesion.

Very serious reactions may occur for very high skin doses exceeding 80 Gy. 

» Will multiple interventional procedures increase the risk of erythema?

Yes.

However, ‘splitting’ the delivery of a particular amount of ionizing radiation (also known as fractionation) over multiple sessions can also reduce the possibility erythema occurrence and its severity that would be seen if the entire dose was received at one time. Radiation effects tend to be cumulative, with the possibility of repair in-between two consecutive exposures. If there is a time gap between two interventional procedures, repair processes enable the skin to tolerate higher levels of radiation; the repair processes depend upon the time gap and the number of times the radiological procedure is repeated. However, data from animal studies indicate that increasing the time gap beyond 24 hours has no effect on the total dose for erythema to occur. 

There is a lack of scientific evidence on the exact relationship between dose effects and X-ray irradiation in the diagnostic range. Information on skin repair is primarily available in relation to high energy radiation as is used in radiotherapy. For example, with three fractions administered at 200 kV, the erythema dose is 11 Gy instead of the 6 - 8 Gy from a single dose at the same 200 kV. With 10 fractions, a total dose of 16.5 Gy is necessary, and with 30 fractions, a total dose of 26 Gy is required to induce the same effect. Repair of injury between fractions is responsible for these differences and the increase in tolerance of the skin to the radiation. The single dose to cause skin necrosis is estimated at 25 Gy. While these figures may not be valid for diagnostic X-rays, the principle remains valid.