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 Table of Contents 
REVIEW ARTICLE
Year : 2022  |  Volume : 45  |  Issue : 1  |  Page : 2-15  

Medical management of ionizing radiation-induced skin injury


1 CBRN Protection and Decontamination Research Group, Division of CBRN Defence, Institute of Nuclear Medicine and Allied Sciences, Delhi, India
2 Department of Pharmacy, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysore, Karnataka, India
3 Department of Textile and Fibre Engineering, Indian Institute of Technology, Delhi, India
4 Department of Chemistry, Miranda House, University of Delhi, Delhi, India
5 Vice Chancellor, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India
6 Department of Chemistry, Shivaji College, University of Delhi, Delhi, India

Date of Submission12-Feb-2021
Date of Decision24-Dec-2021
Date of Acceptance28-Dec-2021
Date of Web Publication28-Jun-2022

Correspondence Address:
Rajeev Goel
CBRN Protection and Decontamination Research Group, Division of CBRN Defence, Institute of Nuclear Medicine and Allied Sciences, Delhi - 110 054
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/rpe.rpe_4_21

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  Abstract 


Skin radiation exposure occurs during planned or unplanned radiation events, such as radiotherapy or nuclear radiation accidents, respectively, resulting into acute and chronic effects depending upon the extent of the radiation exposure or contamination. Radioactive nuclide-induced contaminations severely affect the human skin as skin is the largest organ of the body. Skin radioactive contamination may result into radiation-induced burns that may significantly cause morbidity without any medical intervention. In such scenario, it is necessary to provide priority to severe and life-threatening injuries. The current review provides a holistic picture about the mode of occurrence of radiation injuries, types of radiation burns, local skin effects and pathophysiology, prognosis, diagnosis and treatment, and challenges in the management of radiation wounds. Further, the review also includes the dressings used for irradiated wounds and comparison of amniotic and silver dressings, which possess potential bactericidal and wound-healing properties.

Keywords: Contamination, cutaneous radiation injury, dressings, wounds.


How to cite this article:
Ojha H, Choudhary V, Sharma D, Nair A, Sharma N, Pathak M, Shivkumar H, Sharma RK, Kaushik V, Singhal R, Goel R. Medical management of ionizing radiation-induced skin injury. Radiat Prot Environ 2022;45:2-15

How to cite this URL:
Ojha H, Choudhary V, Sharma D, Nair A, Sharma N, Pathak M, Shivkumar H, Sharma RK, Kaushik V, Singhal R, Goel R. Medical management of ionizing radiation-induced skin injury. Radiat Prot Environ [serial online] 2022 [cited 2022 Aug 13];45:2-15. Available from: https://www.rpe.org.in/text.asp?2022/45/1/2/348729




  Introduction Top


Skin is a superficial and the largest organ in the human body. CBRN attacks are now a stern reality and pose serious challenges for both developed and developing nations. It is anticipated that terrorists may cause radiation injury by triggering radiological dissemination device, deploying radioactivity in public areas, attacking the storage of nuclear materials, and setting off a nuclear weapon or atomic bomb.[1] Besides this, hazards during radiation therapy; occupational hazards; mishandling of medical or industrial radioactive sources; mishaps while shipping radioactive materials; nuclear reactor accidents, etc. can also lead to multiple casualties.[1],[2] Globally, the radiation emergency assistance center training site estimated around 428 accidents and 126 deaths.[1] Skin is the organ that is primarily affected by radiation emitters and can get easily incorporated into human skin and underlying tissues.

Ionizing radiation (IR) including gamma rays and medical X-rays may cause serious damage to body tissues due to their strong penetrating power.[2],[3] Generally, radiation burn is a common symptom that is observed during therapeutic practices using IR and requires an initial assessment, timely intervention, and treatment of the patient.[2] Radiation injuries due to therapeutic radiation are more common than an intentional attack or due to an accidental nuclear accident. Thorough knowledge of the pathophysiology of radiation burn, public health awareness, and control measures can help minimize radiation-induced skin damage. IR produces free radicals which react with biological macromolecules such as DNA and RNA that cause molecular modifications, incorrect chromosomal segregation, and mitotic death induced by radiation.[4],[5]

In the past, the antimicrobial properties of silver were explored to make water suitable for drinking.[6] Metallic silver can be utilized medically for burn treatment, textile fabrics, dental materials, sunscreen lotions, water treatment, etc. Silver dressings can be used topically for the radiation wounds and burns due to their potential antibacterial and wound-healing properties.[7]


  Ionizing Radiation Injuries Top


Radioactivity can affect any living system by exposure via either electromagnetic radiations or subatomic particles. Electromagnetic radiation is a radiant energy which has no mass and travels like a wave through space and material. Day-to-day examples of electromagnetic radiation include sunlight, microwaves used in cooking, use of X-rays for therapeutic and diagnostic purposes, and radio waves used for transmission of television and other related signals. A radiation can travel through both the materials and space through which it traverses. Any radiation can be ionizing depending upon its energy packets. Energy packets refer to the amount of energy a radiation can deposit locally in the medium through which it traverses its path. A typical ionizing event witnesses 33 eV deposition of the energy, and a chemical bond like C = C requires 4.9 eV of energy for bond disruption.[8] Thus, one can assume the strength of the IR and its related biological damage. All electromagnetic radiations are not harmful, and those with high-energy packets cause biological damage. Thus, the deleterious effects of IRs depend on its frequency or its capability to deposit a large amount of energy in the local environment. The examples of ionizing electromagnetic radiations are X-ray and gamma rays.

Particulate radiation, including alpha, beta, positron, neutron, cosmic rays, electrons, and other heavy charged particles[8] unlike electromagnetic radiation, does not travel as a wave rather as particles. These particulate radiations are produced when high-speed charged particles hit a target material. In the case of neutrons, when some radioactive material undergoes fission reaction, there is an additional possibility of observing neutrons.

Biological damage occurs due to the penetration power of IRs. In case of skin as a medium, alpha particles have insignificant penetration, while beta particles can penetrate up to a few millimeters deep in the skin. Alpha-emitting particles may pose radiological hazard only if taken into the body via inhalation or ingestion, or if these enter the system through contamination. Since beta radiation can pass up to few millimeters into the skin surface, these are of prime importance and majorly involved in radiation-induced burns on the skin. Compared to particulate radiation, both the X-rays and gamma rays have more penetrating power and can cause serious radiation burns if exposed locally via high beam. Therefore, beta particles, gamma rays, and X-rays are commonly involved in skin burns as a result of radiation exposure.[9] Radiation injuries include any morphological or functional changes occurring in healthy tissues. IRs produce charged particles called ions with the removal of a negatively charged electron from an atom.

IR can interact with a biological system in two ways, viz., radiation exposure and radiation contamination. In case of radiation exposure, long-term exposure of small amount could lead to genomic instability or cancer, whereas large amount of exposure to radiation could trigger radiation sickness such as acute radiation syndrome and skin burns.[8] There is a difference between radiation exposure and contamination. Radiation contamination occurs when the radioactive material in the form of a liquid droplet or dust particle is inhaled, ingested, or deposited on the body surface such as skin, hair, or other open and exposed parts of the body. Radiation exposure occurs when the whole part of the body absorbs penetrating IR from an external radioactive source.[8] Shielding of the skin from radioactive material or radiation is required. Materials such as lead, steel, or concrete can shield humans from positrons. Neutrons are emitted from a few radioactive materials. These can travel very long distances in air. They are not interactive and cause damage to tissues, depending on their energy. Hydrogen, water, and paraffin are excellent shields for neutrons. Gamma rays and X-rays are pure IR but with lower ionization capacity than particulate radiation. Shielding from gamma rays or X-rays requires lead, steel, or concrete.

IR damages the tissues unevenly depending on the extent of radiation dose absorbed, type of radiation, rate of exposure, level of emitted energy, surface exposed to radiation, the capacity of penetration, the capacity of reflection, and the part or area of the body exposed. Symptoms tend to appear, ranging from local (e.g., burns) to systemic (e.g., acute radiation sickness).[10] Diagnostic measures include a detailed history of exposure, symptoms, or signs, and in rare cases, radiation detection equipment was utilized to recognize the specific radionuclide involved in the contamination. After such accidents, management measures should be focused on minimizing exposure-associated traumatic injuries, decontamination, and supportive measures. Patients experiencing severe acute radiation sickness may require reverse isolation and bone marrow support. Uptake of inhibitors or chelating agents is recommended for the patients internally contaminated with certain radionuclides. The duration between exposure and onset of symptoms or signs, symptoms severity, and the lymphocyte count in the first 24–72 h can provide information on prognosis.[1]

The Chernobyl nuclear power plant accident victims were adversely affected by β-radiation emission (strontium-90) resulting in “beta burns.”[11] Accidents in nuclear power plants may lead to either the whole-body or localized exposure and accumulation of radioactive matter in the body, eventually causing contamination. Based on the degree of infiltration and the amount of dose absorbed in the various parts of the body, the symptoms begin to appear.[12]

Various modes of radiation exposure are presented in [Figure 1]. Acute skin reactions due to radiation usually begin with local erythema due to capillary dilatation in the dermis with concomitant edema. With an increase in radiation dose, epilation, desquamation, and radiation pigmentation ensue. The changes in the inflammation process occur subsequently that contribute to worse and it is referred to as radiodermatitis. Moist desquamation manifests in the worst cases of radiation exposure or contamination.[2]
Figure 1: Graphical abstract

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Exposure and contamination

There are two possible ways through IR may affect any biological system, viz., radiation exposure and radiation contamination. To understand the classification of radiation-induced damage, it is vital to understand the difference between exposure and contamination. When the human skin or any surface comes in contact with radioactive materials, it is referred to as radioactive contamination. However, fully or partially exposure from a radiation source kept at a distance, is termed as radiation exposure. In radiation exposure, the exposed person cannot contaminate others, equipment, or surfaces.[13],[14] There is perceptible occupational hazard associated both in the form of radiation exposure and/or radiation contamination during handling, transportation, and storage of radioactive materials.

Radiation contamination is further of two types that is internal contamination or external contamination. Radioactive material in the form of dust, liquid, or powder may come in contact with a person's clothes, skin or hair etc. and can remain adhered to them. This type of contamination is called as external contamination. However, internal contamination occurs when a radioactive material is internalized through inhalation, ingestion, or absorption of radioactive materials. The chances of internal contamination increase in case of traumatic injuries as the radioactive materials can pass into the biological system through damaged or broken skin. Isotopes of technetium and iodine are used in very small amount for diagnosis of certain pathological conditions, however, mishandling or human error resulting in over dosing could prove fatal and may cause accidental large-dose contamination.[15]


  Burns and Wounds Top


The skin forms an effective physical barrier against any kind of external stimuli, which may lead to a pathological condition. Skin is the largest organ of the human body, and it is the most vulnerable to radiation-induced stress such as radiation injury. It is due to the highly proliferative and extremely radiosensitive skin cells, for example, basal keratinocytes, melanocytes, and hair follicle stem cells.[16],[17] Such radiation-induced damage ensues the release of free radicals causing double-strand breaks in nuclear DNA and causes damage to rapidly proliferating cells.[16],[17],[18] About 95% of the patients are prone to radiation skin reactions while undergoing radiation treatment for cancer.[17],[19] Besides, radiation-induced skin injury may also occur due to an industrial incident or terrorist-sponsored accident or nuclear radiation accidents.[20]

In addition to these pathologies, the traumatic injuries such as burns manifest either after nonlethal or sublethal exposure of radiation or radioactive contamination by deposition of radionuclide into the skin. In these scenarios, it has been observed that, without medical management, the mortality rate may rise up to 12%–75%.[21] Mishandling of radioisotopes can also result in severe radiation burns where late effects include dermal atrophy and telangiectasia.[22],[23] [Table 1] and [Table 2] provides information about various local skin reactions, occurrence dose, time of onset, and their treatment.
Table 1: The early symptoms, dose, time of onset of local skin reactions, and their treatment

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Table 2: The late symptoms, dose, time of onset of local skin reactions, and their treatment

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Local tissue injuries

There are different terms that are used to explain the pathologies involved in the radiation-induced wounds, viz., radiation dermatitis, local radiation injury, and cutaneous radiation injury. Although these seem different, all of them are used collectively to describe skin injury from radiological contamination or exposure. These injuries may occur concomitantly on the entire body due to even partial radiation exposure or contamination.[13] These injuries may be large enough to cause damage other body organs; however, radiation dermatitis is usually limited to radiotherapy (RT) skin effects.

Acute radiation dermatitis

Radiation exposure, whether planned or unplanned, may result in acute skin effects, and acute phase with definite changes was observed within 90 days. Acute radiation dermatitis is characterized initially by erythema. Erythema may manifest hours after radiation exposure and subside within hours to days.[18] Acute dermatitis phase normally reaches its peak from 7 to 14 days, with prominent erythema with marked pink hue mediated by cytokines after the exposure. During the course, repopulation of epidermal keratinocytes and reactivation of immune system can reverse the acute phase symptoms.

Chronic radiation dermatitis

Radiation dermatitis may occur with acute erythema and desquamation. Skin appears to be relatively normal after radiation exposure for quite a time. Chronic skin effects may owe from aberrant or malfunctioning in proinflammatory and profibrotic cytokines. Postinflammatory hypopigmentation and hyperpigmentation, xerosis, and hyperkeratosis are common symptoms that occur during radiation dermatitis after the resolution of acute radiation dermatitis phase. Persistent telangiectasia occurs after an increased dose with acute grade III injury and moist desquamation. Persistent poikilodermatous alterations are manifested by hyperpigmentation and hypopigmentation, atrophy, and telangiectasia, indicating a significant cutaneous injury. Permanent loss of skin appendages and nails may occur along with alopecia and less sweating. Necrosis is commonly observed with high-dose RT, manifesting as a late consequential injury, and is characterized by failure to heal, dermal ischemia, and acute dermatitis.[18]

Fibrosis

It is mainly evident in radiated skin and subcutaneous tissue. Reactive oxygen species presence results in altered production of abnormal myofibroblasts with abnormal production of collagen.[24] Symptoms include thickened fibrotic skin at the irradiated site and constraint in movement. Treatment with pentoxifylline and α-tocopherol has been shown to be effective. However, this dual drug combination given for long basis has been shown to worsen the fibrotic areas.[24]

Lymphedema

It is a common after-effect of RT and is often defined as build-up of fluid in the body's tissue. It is a long-term condition which is not completely curable but medically can be managed. It mostly affects the arms, hands, and fingers but can also affect the torso, head, neck, etc. Mechanisms of occurrence of lymphedema includes depletion of capillary lymphatics and apoptosis of endothelial cells of the lymphatic system.[24] The treatment including modalities includes blocking of TGF-beta 1, a chemical modulator that promotes lymphatic regeneration.[25] Treatment along with hyperbaric oxygen therapy (HBOT) is often attempted with patients suffering from lymphedema, but mixed responses have been observed.[26]

Radiation wounds

Irrespective of the cause, a wound is generally defined as a disruption or injury to the normal organization and function ensuing from a simple or harsh break in the skin and may extend to its underlying tissues, for example, subcutaneous tissue, tendons, nerves, muscles, and bone.[27]

Depending on the kind of healing process involved, wounds are classified into acute or chronic. Acute wounds heal entirely in the anticipated time period ranging from 8 to 12 weeks with minimum scarring.[27] These wounds include mechanical injuries such as penetrating wounds by gunshots, knives, surgical wounds by incisions, burns, chemical injuries occurring from corrosive chemicals, electricity, radiation, and thermal sources.

On the other hand, chronic wounds occur due to tissue injuries and heal at a slower pace. Normally, these wounds require 12 weeks to heal and can recur frequently. More often, they are profoundly contaminated and involve serious tissue damage and loss, which, in turn, may affect its vital and underlying tissues such as bones, nerves, and joints. Chronic wounds often do not heal and require substantial time period to heal, due to repetitive damage to the injured site, pre-existing or causal physiological conditions such as diabetes, inadequate treatment, continuous microbial load, and host-related factors.[27]

Acute wounds are characterized by a low level of bacteria, lower number of inflammatory cytokines, low levels of reactive oxygen species and protease, and integral functional matrix. The cells in acute wounds are highly mitogenic and are mitotically competent, whereas chronic wounds are characterized by the high level of MRSA, high inflammatory cytokines, high levels of reactive oxygen species and proteases, and degraded functional matrix. The cells of chronic wounds possess higher mitogenic activity and exhibit senescence.[28]

Radiation wounds can be either acute or chronic. Chronic wounds may occur months or years posttreatment. Chronic wounds are the consequence of compromised healing of wounds and eventually lead to fibrosis, nonhealing ulcers, lymphedema, and radionecrosis.[24] The acute radiation syndrome manifests into nausea, abdominal pain, vomiting, loss of appetite, and bleeding. Chronic exposure to radiation can cause seizures, headache, severe fever, and ataxia and can lead to death.


  Pathophysiology Top


Irradiation through radioactive materials at lower doses may alter the property of cellular proliferation, whereas at high doses, especially in case of internal contamination, it can result in cell death. Highly proliferative cells, viz., basal keratinocytes, melanocytes, and hair follicle stem cells, are extremely radiosensitive.[16],[17] Such radiation-induced damage entails damage to these rapidly proliferating cells and release of free radicals causing double-strand breaks in nuclear DNA. The damage induced by IR is triggered by free radicals formation by the intracellular water radiolysis. Cellular components damage results in tissue hypoplasia, atrophy, and eventually fibrosis.[29]

Additional exposure contributes to the recruitment of inflammatory cells and direct tissue damage, thus hampering the stages of wound healing. Repetitive exposure to radiation produces a sequence of tissue insults to the skin, which deprives the skin and causes difficulty in repairing the existing damage.[19] At a low dose, clustering of nuclear chromatin, enlargement of the nucleus, and apoptosis manifest. High doses result in nuclear mutilation or loss of nuclear membrane, distortion of mitochondria, degradation of the endoplasmic reticulum, and cellular necrosis. Persistent and everlasting impairment in the repair process eventually influences the integrity of the “healed” radiation-induced wound.[19]

Comprehensive knowledge and understanding of the pathophysiology of the injury are essential for treatment. Thermal and radiation burns differ in their pathological mechanisms, progression, and clinical features. Thorough understanding of the pathogenesis of radiation burns will help in the implementation of preventive measures. Cellular DNA is the main target for radiation effect. The radiation burns are usually evident with X-rays or gamma rays used for teletherapy and interventional radiology, whereas severe radiation burns are predominantly evident with the radioisotopes such as cobalt-60 and iridium-192 used for brachytherapy.[2]

The result of radiation exposure depends on factors related to host and radiation. The host-related factors include age; associated concurrent conditions such as developmental or genetic abnormalities, diabetes, and obesity; and internal cellular radiosensitivity. Radiation-related factors include the kind of radiation, energy, ionization or penetration power, overall dose, fractionation, and the time of treatment.[2]


  Initial Assessment and Diagnosis Top


Although burns are caused by innumerable sources, their acute effects remain relatively similar with the exception of chronic effects which are dependent on the extent and depth of the burn. Radiation burns cause acute effects such as erythema, edema, moist desquamation, and dry desquamation. The initial assessment of any burns in the patients should follow the “ABC” rule, which identifies problems in the airway, breathing, or circulation.[30] General measures and first aid treatment include isolating the person from the source, applying ample amount of cold water to the affected area, avoiding the removal of clothing if the burns are extensive, and consulting a burn specialist quickly, especially in case of extensive burns.[30] It is essential to make an accurate assessment of the extent of a burn to calculate fluid volume therapy and to forecast morbidity. Burn assessment should include patient's general condition and environment, type and cause of the burn, location and extent of the burn, depth of the burn, and effects on the individual patient, e.g., mobility, anxiety, and depression.[30] The extent of burn injury is denoted as total body surface area and can be calculated by using the rule of nines, the Lund and Browder formula, or the Palmar method.[31]

Assessment of skin condition and oral mucosa is significant after radiation exposure. Erythema might occur or might not, although its position should be noted since it gives an idea and will help in the determination of areas contaminated and uniformity of exposure. Extensive early erythema occurring in 6 h after exposure is indicative of the development of the cutaneous syndrome. In radiation incidents involving explosions, differentiation should be made between thermal and flash burns and erythema caused by high doses of radiation.[10] Irradiated patients lacking burns or trauma may entail treatment for vomiting and nausea, pain, diarrhea, electrolyte, and fluid losses. 5HT-3 receptor antagonists can be used for the treatment of vomiting. Usually, headache is common and severe at high doses of radiation and can be treated with conventional drugs, but caution to be exercised with the use of aspirin since it may result in bleeding.[10] Treatment is not quite essential for patients with doses of <1 Gy. Mass-casualty incident victims with radiation doses >10 Gy and with serious and combined injuries, that is, burns, and wounds should have supportive care.[32] Further, the victim should be transferred to an unaffected hospital where additional treatment can be provided.

The medical management of victims following nuclear or radiation accident is dependent on the following factors:[10]

  1. The number of victims: Assessment, diagnosis, and initial therapy may be limited if the number of patients is overwhelming
  2. Thermal or conventional injuries: Initial triage, consideration, and treatment must be of prime importance, and treatment of conventional injuries should be the target with the total body or large volume partial body irradiation
  3. The time period after the exposure(s) occurred: Patients presenting soon after irradiation (few minutes to 48 h) will have signs, symptoms, and laboratory results differing from the late presenting patients. Late presenting patients have noted that, after days or weeks, they often suffer from complications such as infections, mucositis, or painful skin lesions.


Information of estimated total dose for each individual, dose rate whether acute, fractionated or protracted, and tissue volume involved or injury to local area is essential to initiate treatment and prognosis. The severity of symptoms, signs, laboratory tests, and complete history of events helps in revealing the possibility, extent, and verification of exposure along with the magnitude of exposure.

Lymphocytes are extremely susceptible to irradiation; this can be confirmed by the decline in the absolute lymphocyte count immediately following exposure to IR.[10] Assessment of absorbed radiation dose is based on the information that about 80%–100% individuals with total body exposure of >3.5 Gy will initially vomit after exposure.[13] Emesis soon after radiation exposure has been accepted as a general indicator of an absorbed acute dose of radiation. Higher the dose, more the exposure, and almost immediately, the victims tend to vomit. Data from accident and therapy patients reveal that an increased body temperature after irradiation is related to radiation dose absorbed.[33] Serum amylase data may be beneficial in providing a better picture and early verification of radiation exposure.[10]

Referral with health and medical physicist, public health officials, or concerned radiation safety officials is advised in the aftermath of radiation incidents. These professionals may assist in essential and immediate steps to prevent injury. In addition, assertion and information of the radiation incident, dosimetry assistance, and recognition of involved internal radionuclide and its treatment can be obtained.[10]

Various diagnostic and assessment methods to recognize the site of damaged tissue, vasculature condition, depth of the injury, and effects on the underlying tissues and structures include laser Doppler perfusion imaging, thermography, nuclear magnetic resonance imaging, ultrasound, serial digital photography, and near-infrared spectroscopy. Serial full blood count test can be conducted to identify total or large-volume partial-body exposure.[10] Of these, clinical examination is widely used, and it accounts for accuracy in 60%–80% cases. Laser Doppler imaging (LDI) is a noncontact, laser-based technique used to measure microvascular flow and is usually performed after a period of 48–72 h following burn. Insufficiency inflow is paralleled with burn depth. LDI precisely predicts the depth of the burn wound in 97% of cases.[10]

Medical assessment of external contamination

Collection and analysis of swab samples of the nose, the ear, and the mouth would help in the assessment of the prospect of internal contamination and identification of the radionuclide.[1],[87] Likewise, analysis of swabs for wounds should be done for nose, ear, and mouth samples. This aids in the assessment of possible internal contamination and radionuclide identification. Samples may be obtained using either saline or moistened swabs to wipe inside the nostril, ear, and mouth. Analysis with an instrument such as Geiger-Muller survey meter helps in the detection of even small amounts of contamination and also differentiates alpha, beta, and gamma particle radiation.

Further, it also helps in quick assessment of contamination in an individual alongwith the identification of the location of contamination.[1] Apart from Geiger-Muller survey meter, gamma or liquid scintillation and multichannel analyzer too can be used for analysis. Similarly, wound samples are also analyzed. Only sample collection varies with respect to wounds.[1] Clothing removal itself decreases contamination on the person by 90%[1],[87] General washing techniques are efficient for elimination of radioactive contamination. If the skin is intact, the wounds can also be washed with tepid soap water for the removal of contaminants. Waterproof dressings should be employed for the protection of noncontaminated wounds, thereby reducing the uptake of radioactive material during decontamination. Gaps in the skin cause enhanced absorption of radioactive matter. Contaminated site of the skin should be decontaminated, and if it persists, it should be covered with a glove and gauze or plastic to encourage sweating. Contaminated hair should be removed by scissors or electric clippers.[1],[87]

Medical assessment of internal contamination

Internal contamination takes place by ingestion or inhalation of radioactive matter. It may also occur by incorporation through wounds. Radionuclide absorption in the body depends on the type of radionuclide, its chemical and physical properties, and its route of entry.[1],[87] In case of suspected internal contamination, urine and faecal samples need to be collected for the next 24h,[1],[87] to evaluate the presence of radionuclides. Catharsis, gastric lavage can be used to assess incorporation and take necessary action. Management measures of internal contamination include reducing the absorption and internal deposition, enhancing elimination, and beginning treatment as soon as a significant dose has been determined in the body. In cases of suspected radiation injury, a complete blood count (CBC) analysis with differential lymphocyte count repeated every 6 h for 48 h needs to be collected. The analysis can be performed by first venipuncturing the uncontaminated skin area and collection of sample. The sample is then transferred into a purple top collection tube containing EDTA and the puncture site is covered. This helps in establishing a baseline, and further change over time can be assessed. The decrease in lymphocyte count indicates an early radiation dose. Blood chromosomal analysis is another most accurate method for the estimation of radiation dose. The analysis can be performed by venipuncture in uncontaminated skin area and then transfer of the sample into lithium heparin/EDTA tube and then covering the puncture site. However, this test requires special laboratories, and the results may take several days. Routine urine analysis also helps in determining normal kidney function and baseline for urinary constituents. Care should be exercised to avoid contamination while collecting a sample. Samples should be labeled with the date and time of collection.[1]


  Treatment Top


The possibility of the occurrence of nuclear disasters, radiological events, industrial or terrorist-related incidents cannot be undermined. In case of radiological events, the skin is extremely vulnerable and any skin injury, external or internal contamination, burns, and wounds in these circumstances dramatically increase the risk of human life and any negligence in treatment in the aftermath of radiological event may ultimately cause death.

Initial acute treatment

The initial step is to focus on stabilization of the medically unstable or immediate life-threatening emergencies. Then, issues related to exposure need to be considered. Acute pain may be managed by the administration of acetaminophen and opioids. Nonsteroidal anti-inflammatory agents should be avoided since the patient may be at risk of gastrointestinal bleeding due to mucosal damage, if the estimated dose is >5–6 Gy. Recording of the timing of symptoms and a CBC immediately after the incident help reveal the approximate dose of radiation received by the patient.[13]

The initial protection measures are quite similar for both radiation-contaminated and chemically-contaminated patients. Initially, ensure that the field is safe for entry of responders or caretakers. Priority should be given to unstable medical victims once the area is marked safe. In case any source of further potentially dangerous radiation materials that could cause exposure or contamination is observed, it should be immediately detached. In addition, the victim should be removed from the contaminated area, along with the removal of contaminated clothing. Standard medical history for all injuries and illnesses and history of the radiation incident should be obtained. Support from health physicists should be taken to assist in mocking the incident and dose estimation. A detailed survey regarding radiological contamination of open wounds, the face, and intact skin should be done. Laboratory tests such as initial Complete blood count (CBC) with White blood cell (WBC) and other differentials should be conducted. This can be followed by conducted further blood tests serially every 8 hours until there is a steady decrease the concentration of the radionuclides. If the head and neck region is involved in irradiation or contamination, serum amylase test has to be done for 3 days followed by initial C-reactive protein daily for 3 days. Urinalysis and feces assay could help determine radionuclide, if internal contamination has occurred. Further treatment needs to be followed depending on the medical conditions appropriately.[1]

Systemic treatment

Treatment strategies should lay emphasis on prevention of injury, reduction of infection at the damaged area, impediment of vasculature damage, minimization of pain and promoting wound healing. Therapeutic measures include termination of smoking and intake of nutritional supplements such as Vitamins A, C, and E, using pentoxifylline to lower blood viscosity, thus improving its flow and surgical debridement of devitalized tissue. Silver sulfadiazine and steroids can be used for moist reactions.[10] Recombinant human interleukin 4 (rhIL-4) could be used for bacterial infection in the in vivo radiation burn models.[34] HBOT includes administration of inspired 100% oxygen higher than atmospheric pressure (2–3 absolute atmospheres). This mode of treatment has been used for 30 years for chronic and late radiation injuries[35] and necrotizing soft tissue diseases.[36] HBOT creates the oxygen gradient steeper; thereby, the body identifies the injured tissue and facilitates angiogenesis.[47] Further, it promotes fibroblast growth, neovascularization, collagen formation, epithelialization, reduces tissue oedema and leukocyte bactericidal activity. All these collectively contribute to enhanced and quick healing of the wound in ischemic tissue.[37]

Local skincare and prophylactic measures

Skincare is of prime importance during radiation reactions. Skincare regimens, intervention by a physician at the apt time, and creating awareness among patients and family help to reduce the radiation effects. Despite the availability of many clinically validated products and drugs, there is still no universally accepted treatment for dermatitis. [Table 3] presents topical and systemic drugs for cutaneous radiation injury. Gentle washing of the skin with water and soap should be allowed and practiced daily in patients receiving RT.[20] Hydrophilic preparations act as lubricants and thus can be applied for dryness and scaliness. Colloidal oatmeal baths and steroids are useful for itching.[16] Exposure to sunlight must be evaded.[35] These general interventions might be useful for radiodermatitis. Steroidal ointments such as corticosteroid and beclomethasone creams, hyaluronidase-based creams, Aloe vera gel, sucralfate, and lanoline-free hydrophilic products are used locally on the skin. Applying coconut oil on the skin without friction helps minimize itching and irritation.[2] Using Amifostine[38] and Wobe-Mugos oral hydrolytic enzymes have been reported to reduce radiation dermatitis.[39]
Table 3: Topical and systemic drugs for cutaneous radiation injury

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Erythema and dry desquamation

Mild erythema without symptom does not require treatment; instead, it requires the area to be soft with the application of aqueous cream, whereas erythema with mild irritation requires the application of aqueous cream. Moderate-to-severe erythema should be treated with low-dose steroids only in the case if the aqueous cream fails to resolve. In a randomized trial, topical sucralfate versus placebo, no significant differences in erythema were observed.[40] Likewise, dry and flaky desquamation, peeling of skin require similar treatment as of erythema.

Moist desquamation

It is characterized by intra-epidermal blisters and loss of stratum corneum. It is classified as with and without exudates from an administration point of view. Presence of infection can be established by taking a bacteriological swab.[2] Gentian violet, silver sulfadiazine, and amniotic membrane extracts (Placentrex ointment) can be used for moist desquamation without exudates or infection, whereas if exudates are present without infection, a barrier must be formed rapidly to avoid infection.[2] A hydrocolloid wound dressing, DuoDerm composed of natural and synthetic polymers is used for the treatment of exudative and noninfective wounds.[41] Hydrocolloid offers low pH, which is useful for the treatment of Pseudomonas infections.[42] Application of silver leaf nylon dressings reported lesser radiation reactions and less pain.[43] In a randomized controlled trial, Cavillon No-Sting Barrier film reported decreased intervals of moist desquamation against 10% glycerin cream.[43]

Topically applied pentoxifylline and honey were found to be beneficial for radiation burns following breast conservation surgery.[44] Both were used alone and in combination for burn treatment, and the results showed a significant reduction in cutaneous surface area of the burn. Pentoxifylline boosts microcirculation by significantly enhancing the flexibility of erythrocytes. Honey, a traditional wound-healing agent, possesses tremendous pain-relieving effect.[44] Solcoseryl, a protein-free calf blood extract, is employed for radiation-induced moist desquamation.[41] Ginkgo biloba herb is used for the treatment of poor concentration, memory loss, cerebral insufficiency, and glaucoma. The mechanism of action includes increasing blood flow, platelet-activating factor antagonist, modulation of neurotransmitter and activity of receptor, and prevention of damage to membrane triggered by free radicals. A case–control study of rats whole body exposed to radiation reported that pretreatment with G. biloba extract reported a reduction in oxidative damage induced by radiation owing to its antioxidant properties and free radical scavenging.[45] Becaplermin had been used successfully in treating previously irradiated problem wound.[10]

Surgical treatment

It is one of the best available wound care treatments. Care must be exercised during resection since incorrect and inadequate resection results in pathological changes. Excessive exposure to important structures should be avoided as it may cause bone and cartilage necrosis. Further, problems include secondary hemorrhage, progressive necrosis, and progressive infection. An ideal criterion is to remove altered tissue with good and minute blood supply. Other surgical methods should be avoided in the inflamed tissue. In later stages, operations can be executed, and the skin can be supposed to heal and give good stable coverage.[35] Care must be taken to maintain the excellent condition of the patient, such as normal hemoglobin and nutrition for better wound healing.

Musculocutaneous or well-vascularized flap coverage provides several benefits. They permit movement in kinetic parts, cover laid open structures such as large vessels, tendons, nerves, and pleura bones, and offer a cover by which potential reconstructive surgeries can be achieved.[35]

Currently, the standard cure for deep radiation burn involves initial surgery, followed by a full-thickness skin graft or rotation flaps. rhIL-4 has been reported to efficiently reduce the bacterial infection in the in vivo radiation burn models.[34] Intervention time should neither be too early before the appearance of the clinical image nor too late. A skin substitute, Integra® is used for covering wounds, and it further helps in the granulation tissue formation in preparation of skin graft.[47]


  Wound Dressings Top


The diverse nature of wounds has prompted in the development of numerous types of dressings that act at different stages of wound healing. Till date, there is no single dressing which can provide optimal-healing characteristics for all types of wounds nor for the stages of wound healing.[48]

The moist wound-healing concept has been considered as an archetype for wound healing, and it is now extensively accepted. Presence of adequate amount of moisture in the wound-healing environment has been revealed to increase the rate of epithelialization.[48] Dressings provide a moist environment that increases re-epithelialization. Mechanism of action includes the release of enzymes to destroy necrotic tissue, phagocytosis of debris and bacteria by inflammatory cells, and migration of keratinocyte and fibroblast to the wound.[16] This type of interactive moist healing is used to guard areas that are often exposed to distress.[46] [Figure 2] depicts the ideal properties of a wound dressing.
Figure 2: An outline of the characteristics of an ideal dressing for the wound

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However, there is no such wound dressing that exhibits all the mentioned properties of the ideal wound dressing, but technology is evolving and has advanced beyond the usage of traditional wound dressings such as gauze, lint, and cotton wool. In today's world, there are numerous wound care products available aimed at augmenting the healing. [Table 4] summarizes in brief the various approaches used for the treatment of irradiated wounds.
Table 4: Various approaches for the treatment of irradiated wounds

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Amniotic dressing versus silver dressing: A comparison

Currently, amniotic membrane and silver are used clinically due to their broad and potential activities. Amnion, the innermost extra-embryonic membrane, is mainly used to stimulate the healing of wounds in the skin and eyes as well as ulcers.[49] Few authors have established that amnion possesses antibacterial, wound-healing, and immunomodulatory activities. On the other hand, dressings with silver preparations such as nanocrystalline materials are commercially available. These dressings exert their effect by providing a sustained release of silver ions for delivery into the wound, thereby killing the bacteria. Silver ions through chemical means adhere to dressing material and elicit antibacterial effects on exudates being drawn out of the wound by the action of the dressing.[50]

The amnion membrane has numerous clinical applications. It is mainly used to stimulate the healing of wounds in the skin, eyes, and ulcers. It has also been used in vaginal reconstructive surgery, repair of abdominal hernia, prevention of surgical adhesions, and pericardium closure.[49] Silver dressings too are extensively used in wound care with different chemical forms of silver. Silver possesses antimicrobial properties, which is effective for wound care and is generally regarded as safe. Wound dressing with silver preparations, including nano, have been commercially used.[50] [Table 5] presents a detailed comparison of amniotic and silver dressing, including their source, mechanism of action, toxicity, advantages, and disadvantages.
Table 5: Comparison of amniotic dressings versus silver dressings

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Challenges in radiation wound managements

Despite the various wound dressings and available surgical procedures, the treatment of severe radiation burns remains unresolved. The Chernobyl nuclear power plant accident (1986) had accounted for 4%–50% of skin involvement from emissions of strontium-90 (beta particle) and cesium-137 (gamma particle).[51] Acute effects, viz., blistering, and erythema were seen within a year following accident, whereas late radiation skin effects appeared 14 years following the accident and included epidermal atrophy, telangiectasia, fibrosis, and pigment changes.[51] Hence, radiological effects are often unpredictable. Synergistic action between radiation effects and physical injury is more dangerous than single injuries, and this may induce complications and mortality.[52] In the aftermath of accidents, importance and therapy should be given on conventional injuries, including medical and surgical care and management of the injured site. This includes management of acute radiation sickness, replacement of fluids and platelets, wound cleansing, debridement, and other surgical procedures. The victims should be separated based on the amount of exposure as high and low. Estimation of the radiation dose absorbed by each victim based on dosimetry, laboratory findings, or clinical assessment helps in the triage. Patients exposed to low doses of radiation may need prophylactic antimicrobial therapy and surgical procedures, if necessary, or administration of antimicrobials if the infection persists.[52] Patients exposed to high doses of radiation needs vigorous therapy, selective decontamination, and protective isolation, and this should be started soon after irradiation. Therefore, effective therapeutic strategies and the knowledge of the mechanisms responsible for acute and chronic skin effects from localized or whole-body irradiation are needed. Early therapeutic intervention helps to prevent multiorgan involvement and subsequently multiorgan failure. Clinical dosimetry should be considered for the estimation of the severity of radiation exposure based on clinical signs and symptoms in the victims.[53]


  Conclusions Top


There is a constant risk of nuclear or radiological agents' exposure and contamination accidentally or deliberately by terrorists in the form of weapons of mass destruction (dirty bomb). These agents are lethal, resulting in radiation burns and wounds which cause significant morbidity and mortality. Besides this, additional injuries such as burns and wounds also occur which on delayed treatment results in infection with disease and ultimately to death. Unfortunately, there is no gold standard for radiation-induced skin injury. Initial diagnosis and assessment must be of prime importance after radiation exposure, and active involvement of physician handling radiation, radiation safety officer, public health officials, burn specialists, radiation medicine specialists, and collaboration among interprofessional during radiation accidents will help in prevention and treatment of the damage. Due to its complex pathology and intricacy in clinical management, better understanding and more attempts are required to improve the treatment for radiation-induced burns and wounds. Silver and amnion materials owing to its antibacterial and wound-healing properties are potential candidates for the treatment of radiation-induced burns and wounds.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Tables

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Introduction
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