Radiation injury

Injury to the skin and underlying tissues from acute exposure to a large external dose of radiation is referred to as cutaneous radiation injury (CRI). Acute radiation syndrome (ARS) 1 will usually be accompanied by some skin damage; however, CRI can occur without symptoms of ARS. This is especially true with acute exposures to beta radiation or low-energy x-rays, because beta radiation and low-energy x-rays are less penetrating and less likely to damage internal organs than gamma radiation is. CRI can occur with radiation doses as low as 2 Gray (Gy) or 200 rads 2 and the severity of CRI symptoms will increase with increasing doses. Most cases of CRI have occurred when people inadvertently came in contact with unsecured radiation sources from food irradiators, radiotherapy equipment, or well depth gauges. In addition, cases of CRI have occurred in people who were overexposed to x-radiation from fluoroscopy units.

Early signs and symptoms of CRI are itching, tingling, or a transient erythema or edema without a history of exposure to heat or caustic chemicals. Exposure to radiation can damage the basal cell layer of the skin and result in inflammation, erythema, and dry or moist desquamation. In addition, radiation damage to hair follicles can cause epilation. Transient and inconsistent erythema (associated with itching) can occur within a few hours of exposure and be followed by a latent, symptom-free phase lasting from a few days to several weeks. After the latent phase, intense reddening, blistering, and ulceration of the irradiated site are visible. Depending on the radiation dose, a third and even fourth wave of erythema are possible over the ensuing months or possibly years.

In most cases, healing occurs by regenerative means; however, large radiation doses to the skin can cause permanent hair loss, damaged sebaceous and sweat glands, atrophy, fibrosis, decreased or increased skin pigmentation, and ulceration or necrosis of the exposed tissue.

With CRI, it is important to keep the following things in mind:

• The visible skin effects depend on the magnitude of the dose as well as the depth of penetration of the radiation.

• Unlike the skin lesions caused by chemical or thermal damage, the lesions caused by radiation exposures do not appear for hours to days following exposure, and burns and other skin effects tend to appear in cycles.

• The key treatment issues with CRI are infection and pain management.

Stages and Grades of CRI

CRI will progress over time in stages and can be categorized by grade, with characteristics of the stages varying by grade of injury, as shown in Table 1. Appendix A gives a detailed description of the various skin responses to radiation, and Appendix B provides color photographs of examples of some of these responses.

Prodromal stage (within hours of exposure)—This stage is characterized by early erythema (first wave of erythema), heat sensations, and itching that define the exposure area. The duration of this stage is from 1 to 2 days.

Latent stage (1–2 days postexposure)—No injury is evident. Depending on the body part, the larger the dose, the shorter this period will last. The skin of the face, chest, and neck will have a shorter latent stage than will the skin of the palms of the hands or the soles of the feet.

Manifest illness stage (days to weeks postexposure)—The basal layer is repopulated through proliferation of surviving clonogenic cells. This stage begins with main erythema (second wave), a sense of heat, and slight edema, which are often accompanied by increased pigmentation. The symptoms that follow vary from dry desquamation or ulceration to necrosis, depending on the severity of the CRI (see Table 1).

Third wave of erythema (10–16 weeks postexposure, especially after beta exposure)—The exposed person experiences late erythema, injury to blood vessels, edema, and increasing pain. A distinct bluish color of the skin can be observed. Epilation may subside, but new ulcers, dermal necrosis, and dermal atrophy (and thinning of the dermis layer) are possible.

Late effects (months to years postexposure; threshold dose ~10 Gy or 1000 rads)—Symptoms can vary from slight dermal atrophy (or thinning of dermis layer) to constant ulcer recurrence, dermal necrosis, and deformity. Possible effects include occlusion of small blood vessels with subsequent disturbances in the blood supply (telangiectasia); destruction of the lymphatic network; regional lymphostasis; and increasing invasive fibrosis, keratosis, vasculitis, and subcutaneous sclerosis of the connective tissue. Pigmentary changes and pain are often present. Skin cancer is possible in subsequent years.

Recovery (months to years)

Table 1: Grades of cutaneous radiation injury

Patient Management

Diagnosis

The signs and symptoms of CRI are as follows:

Intensely painful burn-like skin injuries (including itching, tingling, erythema, or edema) without a history of exposure to heat or caustic chemicals Note : Erythema will not be seen for hours to days following exposure, and its appearance is cyclic. Epilation A tendency to bleed Possible signs and symptoms of ARS

As mentioned previously, local injuries to the skin from acute radiation exposure evolve slowly over time, and symptoms may not manifest for days to weeks after exposure. Consider CRI in the differential diagnosis if the patient presents with a skin lesion without a history of chemical or thermal burn, insect bite, or skin disease or allergy. If the patient gives a history of possible radiation exposure (such as from a radiography source, x-ray device, or accelerator) or a history of finding and handling an unknown metallic object, note the presence of any of the following: erythema, blistering, dry or wet desquamation, epilation, ulceration.

Regarding lesions associated with CRI be aware that,

days to weeks may pass before lesions appear; unless patients are symptomatic, they will not require emergency care; and lesions can be debilitating and life threatening after several weeks.

Medical follow-up is essential, and victims should be cautioned to avoid trauma to the involved areas.

Initial Treatment

Localized injuries should be treated symptomatically as they occur, and radiation injury experts should be consulted for detailed information. Such information can be obtained from the Radiation Emergency Assistance Center/Training Site (REAC/TS) at www.orau.gov/reacts/ or (865) 576-1005.

As with ARS, if the patient also has other trauma, wounds should be closed, burns covered, fractures reduced, surgical stabilization performed, and definitive treatment given within the first 48 hours after injury. After 48 hours, surgical interventions should be delayed until hematopoietic recovery has occurred.

A baseline CBC and differential should be taken and repeated in 24 hours. Because cutaneous radiation injury is cyclic, areas of early erythema should be noted and recorded. These areas should also be sketched and photographed, if possible, ensuring that the date and time are recorded. The following should be initiated as indicated:

Supportive care in a clean environment (a burn unit if one is available) Prevention and treatment of infections Use of the following: Medications to reduce inflammation, inhibit protealysis, relieve pain, stimulate regeneration, and improve circulation Anticoagulant agents for widespread and deep injury

Pain management Psychological support

Recommendations for Treatment by Stage

The following recommendations for treatment by stage of the illness were obtained by summarizing recommendations from Ricks et al. (226) and Gusev et al. (231), but they do not represent official recommendations of CDC.

Prodromal Stage —Use antihistamines and topical antipruriginous preparations, which act against itch and also might prevent or attenuate initiation of the cycle that leads to the manifestation stage. Anti-inflammatory medications such as corticosteroids and topical creams, as well as slight sedatives, may prove useful.

Latent Stage —Continue anti-inflammatory medications and sedatives. At midstage, use proteolysis inhibitors, such as Gordox®.

Manifestation Stage —Use repeated swabs, antibiotic prophylaxis, and anti-inflammatory medications, such as Lioxasol®, to reduce bacterial, fungal, and viral infections

Apply topical ointments containing corticosteroids along with locally acting antibiotics and vitamins. Stimulate regeneration of DNA by using Lioxasol® and later, when regeneration has started, biogenic drugs, such as Actovegin® and Solcoseril®. Stimulate blood supply in third or fourth week using Pentoxifylline® (contraindicated for patients with atherosclerotic heart disease). Puncture blisters if they are sterile, but do not remove them as long as they are intact. Stay alert for wound infection. Antibiotic therapy should be considered according to the individual patient's condition. Treat pain according to the individual patient's condition. Pain relief is very difficult and is the most demanding part of the therapeutic process. Debride areas of necrosis thoroughly but cautiously.

Treatment of Late Effects

After immediate treatment of radiation injury, an often long and painful process of healing will ensue. The most important concerns are the following:

Pain management Fibrosis or late ulcers Note : Use of medication to stimulate vascularization, inhibit infection, and reduce fibrosis may be effective. Examples include Pentoxifylline®, vitamin E, and interferon gamma. Otherwise, surgery may be required. Necrosis Plastic/reconstructive surgery Note : Surgical treatment is common. It is most effective if performed early in the treatment process. Full-thickness graft and microsurgery techniques usually provide the best results. Psychological effects, such as posttraumatic stress disorder Possibility of increased risk of skin cancer later in life