Australian Clinical Guidelines for Radiological Emergencies - September 2012

Cutaneous Radiation Injury

Page last updated: 07 December 2012

Cutaneous radiation injury (CRI) occurs when the skin absorbs an appreciable amount of ionising radiation. It may occur in isolation, but in accidental exposures it is often found in conjunction with some degree of Acute Radiation Syndrome (ARS). In a terrorist incident or nuclear explosion, CRI would be found in combination with thermal burns and other injuries.

Consider local radiation injury in the differential diagnosis if the patient presents with a skin lesion without a history of chemical or thermal burn, insect bite, or history of 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. Local injuries to the skin evolve very slowly over time and symptoms may not manifest for days to weeks after exposure.

CRI is never just "skin-deep". The underlying connective tissue, muscle and even bone can be affected without any obvious sign in the early stages. Initial evaluation of the injury is complicated by the many variables that can affect CRI, including the type, energy and total energy deposition of the radiation, the total area exposed and the depth of penetration. ARS, concomitant injuries and underlying medical conditions are added complicating factors.

CRI is notoriously difficult to treat, and suspected cases should be referred for specialist assessment by radiation oncologists wherever possible. Treatment is largely symptomatic, though skin stem cells and colony-stimulating factors are available. Lifelong follow-up is required for severe cases, since damage to deeper tissues may become manifest many years or even decades after the original injury.

Mode of injury

CRI can occur by any modality of radiation, though damage from alpha sources is rare because of the protective effect of the keratin layer. Beta radiation, low-energy X-rays and slow neutrons will penetrate a few centimetres and so deposit most or all of their energy into the skin and connective tissues. For high-energy X-rays, gamma rays and fast neutrons, energy deposition in the skin will only be a small percentage of the total tissue dose. It follows that for any given external dose in Grays, the skin will suffer proportionately more damage from beta particles, low-energy X-rays and slow neutrons. It also follows that an external dose of gamma rays or neutrons sufficient to cause CRI will have severe effects on the underlying tissue.

External contamination is rarely active enough to cause acute CRI. Prompt decontamination (removal of clothing and washing of exposed skin and hair) is generally all that is required. If the contaminant was particularly active the patient should be advised of the risk of skin cancer in later years.

External exposure may be localised (partial body) or general (whole body). Local exposure is usually from a beam source or a misplaced radiotherapy or industrial source; these exposures are often unnoticed at the time and may present with established or recurrent ulcers. Whole-body exposure may occur in criticality accidents or as the result of a nuclear detonation, and such cases may be complicated by thermal or blast injuries.

Mechanism of injury

As for all other radiation injuries, cellular damage occurs as a result of energy transfer. DNA strands are broken, proteins are disrupted and free radicals are formed. Pro-inflammatory genes and cytokines are up regulated, anti-oxidant capacity is reduced and a cascade of cell damage follows.

Extensive damage leads to cell necrosis, tissue breakdown and visible signs such as epilation, blisters, sloughing and ulcers. Lesser damage may cause little in the way of acute signs, but can contribute to apoptosis (early cell death) with subsequent atrophy, fibrosis and/or late ulceration.

The most sensitive cells are the dividing cells in the basal layer of the dermis, but all levels can be affected.

Presentation

The threshold for deterministic skin effects is approximately 6 Gy, though there is some variation in sensitivity among individuals. The majority of cutaneous radiation injuries are not diagnosed at the time of irradiation, but weeks or months later, after symptoms and signs have developed.

Erythema immediately following an exposure indicates that the patient has suffered a thermal or chemical burn in addition to radiation exposure, which constitutes a combined injury. Pure radiation damage causing erythema within 2 hours indicates a severe injury (>60 Gy). Extremely high doses of radiation (>100Gy) may produce a tingling or burning sensation in the skin.

Table 15.1 shows the typical response and time of onset of skin reactions to gamma irradiation. Exposure to beta or neutron irradiation results in an earlier and more severe skin response per Gray, but there may be less damage to underlying tissues.

Table 15.1 - Skin response to gamma irradiation
SignsDose range (Grays)Time of onset (days)
Erythema3 - 1014 - 21
Epilation>314 - 18
Dry desquamation8 - 1225 - 30
Moist desquamation15 - 2020 - 28
Blister formation15 - 2515 - 25
Ulceration >2014 - 21
Necrosis>25>21
Reference: IAEA SRS-02 - Diagnosis and Treatment of Radiation Injuries, Vienna 1998

Assessment

Although CRI, like other forms of acute radiation damage, is dose-dependent, cutaneous signs are difficult to incorporate into dosimetry because of the individual variability and the relatively late manifestation of injury. Assessment is largely clinical. The extent of inflammation (in the early stages) and tissue fibrosis/atrophy (in the later stages) may be mapped by ultrasound, thermography, CT/MRI, and/or radio-isotope scans.

CRI is assessed against eight criteria (comprising symptoms and signs) and divided into four degrees which have some relation to the body's capacity for self-repair.

Table 15.2 - Assessment of acute CRI
Symptoms / signs(1)Degree 1Degree 2Degree 3Degree 4
erythema (2)minimal, transientmoderate; isolated patches;
<10% BSA
marked; isolated or confluent patches; 10-40% BSAsevere
>40% BSA
sensationpruritisslight, intermittent painmoderate and persistent painsevere and persistent pain
swelling/oedemapresent but asymptomaticsymptomatic, with tensionsecondary dysfunctiontotal dysfunction
blisteringrare, sterile fluidrare, haemorrhagebullae, sterile fluidbullae, haemorrhage
desquamationabsentpatchy, drypatchy, moistconfluent, moist
necrosisepidermal onlydermalsubcutaneousmuscle or bone
hair lossthinningpatchy, visiblecomplete, reversiblecomplete, irreversible
onycholysisabsentpartialvariablecomplete
(1) Symptoms and signs usually appear in this order
(2) Erythema should be mapped and documented frequently

Reference: Fliedner et al: Medical Management of Radiation Accidents - Manual on the Acute Radiation Syndrome, London, 2001

As with ARS, there are five chronological stages of CRI: prodrome (first wave of erythema), latent period, manifest illness (including the second wave of erythema), recovery and late effects. The duration of each stage varies with the total exposure. In cases of non-uniform exposure (such as local injuries or criticality accidents) two or more stages may be present simultaneously in different parts of the body.

Treatment

As with any extensive skin injury, general supportive measures are essential. The skin is a vitally-important organ, with roles in controlling hydration, infection, temperature regulation and nutrition. It follows that patients with moderate or extensive skin injuries are susceptible to dehydration, recurrent and systemic infection, hypothermia and nutritional deficiencies. In addition to that, radiation damage causes a cascade of inflammatory effects that can have deleterious effects on the surrounding tissue and other organs.

If acute radiation exposure has been identified, immediate treatment with cool water may reduce the development of inflammation. For severe cases, anti-histamines, non-steroidal anti-inflammatory drugs (excluding aspirin) and gluco-corticosteroids are useful (although care must be taken not to impair clotting or the immune system any further).

KGF (keratinocyte growth factor) may help to stimulate regeneration of damaged skin but will not have any macroscopic effect for some weeks, and must be used in addition to all other modalities, not instead of them.

Pain is a prominent feature of CRI and is difficult to treat. Mild cases may obtain adequate analgesia with NSAIDS and mild opiates such as codeine, but severe cases will require a strong opiate, plus corticosteroids and/or neuroleptics such as promethazine and haloperidol. In the most severe cases surgical sympathectomy may be required.

Fluid replacement will be needed for extensive or deep cutaneous injuries, but the total fluid requirement in the first 24 hours will be less than that for the equivalent thermal burn. After the first 24 hours, fluid replacement should be tailored to the patient's condition. Severe CRI, with extensive skin loss, may require up to 10 litres/day fluid replacement.

Temperature regulation is impaired. In the first few days the inflammatory reaction causes a rise in body temperature. After that, evaporative losses from denuded skin are likely to cause hypothermia, and a fever is a sign of infection.

Infection is a major complication where the skin's integrity has been compromised, and is more likely when the body's haematopoietic system has also been affected. The body's own commensal bacteria are a major source of infection, and efforts should be made to reduce the bacterial load of the skin and the gut, with antiseptic washes and non-absorbable antimicrobials.

Severely affected skin (degree 4) will not heal, and consideration should be given to debridement. It is difficult to apply the surgical “48 hour rule" in skin injuries, because it is almost impossible to delineate the boundary between viable and non-viable skin the first few days. Imaging techniques, as described above, may assist in planning skin and tissue debridement. Autologous skin grafts are the preferred replacement wherever possible, but in extensive CRI there may be insufficient unaffected skin to use as donor sites. Graft take-up rates may be adversely affected by damage to underlying tissue.

Current research into post-exposure anti-inflammatory and anti-oxidant treatments may prove of use. Mesenchymal stem cells may be able to regenerate denuded skin, but are not yet widely available.

Should stem cells or bone marrow transplant be considered for the treatment of severe ARS, bear in mind that irradiated skin is much more sensitive to graft-versus-host disease (GvHD) than normal skin, and skin changes will be seen at very mild levels of systemic GvHD.

Follow-up

CRI requires life-long follow-up.

Even where skin has been repaired or grafted, there will be some damage to the adjacent and/or underlying tissues that may become manifest many years or even decades after the original injury. Pigment changes, keratosis and telangiectasia are very common. Recurrent ulceration, vasculitis and deep tissue fibrosis are common sequelae, and may be accompanied by chronic pain. Skin cancer (particularly basal cell carcinoma) is also common.

Prevention

In some cases, such as planned radiotherapy, it may be feasible to use prophylactic measures to reduce cutaneous and mucous membrane damage. There are only two preparations currently available in Australia:
      1. amifostine, an organic thiophosphate pro-drug, which must be given 15-30 minutes prior to radiotherapy, and often requires the use of a 5HT3-antagonist such as ondansetron; and
      2. palifermin, a keratinocyte growth factor.

* Sunburn may be considered as a very mild form of CRI. Because the causative radiation is primarily in the UV range, which does not penetrate below the dermis, effects are localised to the skin and rarely exceed Degree 1 in the Fliedner, et al classification.