Radiation Ulcers

Wilhelm Konrad Roentgen discovered x-rays in 1895. The realization that radiation can cause tissue injury followed shortly thereafter. Many different forms of radiation have since been discovered, and applications have been developed for medical, industrial, and military use.

The common pathway of radiation injury to tissue, regardless of the source of the radiation, is interaction of the radiation energy with DNA that causes structural damage to the DNA. Depending on the precise area of injury in the cell, the damage may be repaired, cause cell death, or cause delayed effects. This damage can lead to both acute and chronic tissue effects.

Ionizing radiation may come from high-energy photons that can be the product of natural decay of radioactive material, such as gamma rays, or the product of artificial bombardment of electrons onto Tungsten, such as x-rays. Gamma rays and x-rays can be manipulated to control the amount of energy and the depth of penetration. The energy delivered to the tissues is measured in electron volts. Orthovoltage radiation is used in therapeutic radiation, and includes radiation at 80-400 keV. Supervoltage radiation delivers energy in excess of 1 million V.

Radiation can also be produced by high energy particles that are a product of radioactive decay. Alpha particles are helium nuclei emitted by various elements, including radium. Alpha particles penetrate poorly but can be taken up in local tissues. Beta particles are electrons. They penetrate the skin superficially and can be useful in treating relatively superficial skin conditions, such as mycosis fungoides.

Brachytherapy is radiation therapy delivered with a short distance between the radiation source and the target. Many radioactive isotopes are used, such as iodine-125, gold-198, and cesium-137. Needles filled with radioactive seeds, mechanical appliances, permanent seeds, and other modalities can be used.

Radiation delivery is measured by the amount of radiation absorbed by a gram of tissue. One rad is equal to 100 ergs of energy absorbed per gram of tissue. The most common unit of measurement is the gray, which is equal to 100 rad.

Frequency

The true incidence of radiation injury to normal tissue is unknown. An acceptable short-term complication rate from radiation therapy is in the range of 5-15%. The long-term complication rate is unknown and, of course, affected by long-term survival rate. As cancer therapy becomes increasingly effective, patients are living long enough to have the adverse late effects of their radiation treatment.

In patients who underwent cardiac fluoroscopy for percutaneous coronary intervention, Wei et al, in a retrospective study, found the resulting incidence of radiation ulcers to be 0.42% (nine out of 2124 patients). ^[3]

The acute effect of ionizing radiation is direct cell damage to DNA. This damage may cause immediate cell death, prevent proliferating cells from dividing, or induce apoptosis. The late effect is fibrosis. ^[4] The mechanism of fibrosis production is unclear, but it may involve proinflammatory and profibrotic cytokines, such as tumor necrosis factor-alpha. The fibrosis is progressive.

Tissues affected by acute high-dose radiation, as in industrial accidents, manifest progressive obliterative endarteritis culminating in tissue necrosis. ^[5] Long-term radiation injury results in fibrosis of the dermal and subcutaneous tissues. Elastin fibers are fragmented. The skin loses its rete pegs. The number of blood vessels may be normal; however, fibrosis around them impairs their ability to contract. Electron microscopy may show dehiscence of endothelial cells and microthrombi. ^[6]

Radiation damage to cells can also lead to future malignancies. These may arise in chronic wounds due to radiation damage. They can also be the cause of nonhealing wounds.

On a cellular level, radiation-induced damage can be direct or indirect. Direct damage results from the hits to, or radiation absorption by, the cells. In contrast, indirect damage occurs when the radiation causes cellular water to release free radicals, which in turn combine to make cytotoxic peroxides. ^[7] Direct effects of radiation can affect cellular DNA, which, when altered, may lead to cellular destruction or aberrant cellular replication and malignancy.

These direct and indirect cellular alterations also occur at the level of the fibroblast. In the development of soft tissue wounds and ulcerations in irradiated fields, extensive research implicates fibroblast dysfunction and depletion as culprits because of decreased collagen deposition in soft tissues. Although most investigators agree that vascular injury also inhibits wound healing, Rudolph et al question this notion. ^[8] They suggest that oxygen tension is not altered in irradiated tissues compared with nonirradiated fields and that the onus of impaired wound healing falls on this fibroblast dysfunction. ^[9] Some laboratory evidence indicates that local treatment of radiated wounds with transforming growth factor (TGF)-beta and fibroblast growth factor (FGF) improves tensile strength in acute radiated wound models. ^[10]

The 3 types of radiation injury are acute, subacute, and chronic.

Acute injury refers to radiation exposure that often occurs in a setting such as an industrial accident. It is usually caused by orthovoltage radiation in the range of 5000-10,000 rads. The effects on the skin and exposed soft tissues are like those of a thermal burn, with alterations and destruction of the basal cells of the epidermis, though these effects are slower and more progressive than those due to thermal burns. Erythema results and may be recurrent. Along with erythema, the patient has pain, edema, itching, and eventual desquamation of the skin. This desquamation can progress to soft tissue necrosis and obliterative endarteritis. Superimposed infection also may complicate the clinical course.

Subacute injury differs from the acute form in that it is caused by recurrent exposures to radiation over time, as with therapeutic radiation. This type of radiation tends to be of lower energy than that observed in occupational or environmental exposures. It also causes cutaneous erythema and edema, but the erythema tends to be transient and necrosis is usually absent. Another characteristic finding after multiple radiation treatments is hyperpigmentation and a woody induration of the soft tissues. In terms of vascular effects, studies have demonstrated the following changes in irradiated vessels: decreased smooth muscle; increased collagen levels with fibrosis and thickening of the walls; hyaline degeneration and breakdown of elastic lamina; dehiscence of endothelial cells; and fibrinoid necrosis and microthrombi in the lumina leading to ineffective delivery of oxygen, other vital nutrients, and antibiotics.

Chronic injury results from long-term exposures and typically results from repeated occupational exposures (eg, in radiology technicians). The injuries are similar to those noted above but tend to be more pronounced. This is particularly true of vascular damage. Fibrosis and thrombosis progress to an obliterative endarteritis and its attendant ischemia.

Given the progressive nature of radiation damage, a soft-tissue ulceration may develop at any time after radiation exposure. This ulceration may be large, or it may initially manifest as a draining sinus.

In patients who have undergone breast cancer surgery, Ma et al classified chronic radiation-induced ulcers of the chest wall as follows ^[11] :

• Mild - Less than 10 cm ², ulceration to the subcutaneous layer, ulcer base containing relatively healthy granulation tissue, and no disorders of upper limb movement
• Moderate - Over 10 cm ², ulcer base containing partially exposed bone and no healthy granulation tissue, and partial sensory and motor disorders of the upper limb
• Severe - Over 100 cm ², ulcer base revealing obvious collarbone and/or rib osteonecrosis, and total loss of upper limb function

Indications for treatment of radiation ulcers include control of infection and prevention of sepsis, pain control, management of the malignant potential, and closure of wounds.

Radiation ulceration may affect skin, underlying soft tissues, and bone. The effects of injury may be seen beyond the area of treatment. Before reconstructive surgery is undertaken, the physician must thoroughly evaluate the probable extent of injury and the effect of the chosen reconstructive method.

Radiation injury of deep tissues may be underestimated. Radiated tissue heals poorly by secondary intention. Therefore, reconstructive methods that lead to primary wound healing are strongly preferred. Exposure of vital structures should be avoided unless the reconstructive plan allows for their immediate coverage.