ToxCard: Radiation-Induced Skin Injury

Authors: Ahmed Mashal (Emergency Medicine Resident, Atrium Health’s Carolinas Medical Center); Ann-Jeannette Geib, MD (Emergency Medicine Attending, Medical Toxicologist, Atrium Health’s Carolinas Medical Center) // Reviewed by: Christopher Counts, MD (Medical Toxicology Fellow, Rutgers New Jersey Medical School, Newark, NJ); Cynthia Santos, MD (Emergency Medicine Attending, Medical Toxicologist, Rutgers New Jersey Medical School); Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)

Case: 

A 60-year-old woman with a history of tonsillar carcinoma presented to the hospital with an extensive skin lesion. She had previously undergone carbon ion radiotherapy, receiving a cumulative dose of 75 GyE in 20 fractions over two courses from December 2020 to January 2021. Symptoms of radiation-induced skin injury began on the eighth day after initiating radiotherapy, and by January 18, 2021, the lesion had progressed to Grade IV radiation dermatitis. Her vital signs were within normal limits. Physical examination revealed a wound on the right neck; it was 11 x 12 cm with 75% black eschar and 25% red granulation tissue. The patient also reported significant pain and had a Hospital Anxiety and Depression Scale (HADS) score indicating severe anxiety and depression.¹  

Questions: 

1. What is the most likely diagnosis for the skin condition observed in this patient?
2. What is the primary mechanism underlying radiation-induced skin injury? 
3. What are the typical clinical features of radiation-induced skin injury?
4. What treatment could be used in managing radiation induced skin injury?

Background:

Here, radiation-induced skin injury (RSI) will refer to skin injuries resulting from medical radiation therapy, excluding those arising from radiation dispersal devices (“dirty bombs”), nuclear accidents, or occupational exposures.

What Is Radiation-induced Skin Injury?

• RSI occurs when ionizing radiation damages skin tissues. This condition can range from mild erythema to severe necrosis.² Ionizing radiation used in medical treatment can be broadly categorized into external beam radiation therapy (EBRT) and brachytherapy. EBRT delivers high-energy beams such as X-rays or gamma rays from outside the body to target tumors. Brachytherapy involves placing a radioactive source directly inside or adjacent to the tumor, offering localized high-dose radiation. The exact method chosen is based on tumor type, location, and patient-specific factors.^3,4
• RSI, or radiation dermatitis, arises from the complex effects of ionizing radiation on skin tissues. 
  • The primary mechanism is DNA damage in basal epidermal cells, which impairs cell renewal. 
  • Additionally, senescent keratinocytes release pro-inflammatory signals, activating immune cells and recruiting neutrophils, which exacerbate tissue injury.⁵
  • Reactive oxygen species (ROS) generated by radiation amplify cellular damage, targeting lipids, proteins, and DNA.⁶ 
  • In chronic cases, fibrosis develops as TGF-β drives fibroblast-to-myofibroblast transformation, resulting in excessive extracellular matrix deposition.⁷ Additionally, vascular damage reduces blood flow, worsening hypoxia and tissue breakdown.⁸ 
• These processes manifest as erythema, desquamation, ulceration, and fibrosis, highlighting the need for effective prevention and treatment strategies.
• In 2016, about 3.05 million cancer survivors in the United States received radiation therapy. This figure is expected to rise to 4.17 million by 2030.⁹

Figure 1. Structure of the epidermis, including its layers and functions. Adapted from Cleveland Clinic¹⁴

Clinical Features of Radiation-Induced Skin Injury:

• Early Effects (hours to weeks): Erythema, edema, and desquamation.
• Late Effects (months to years): Fibrosis, pigmentary changes, and chronic ulcers.^2,13
• Healing from radiation-induced skin injuries depends on the dose of exposure. 
  • Mild doses (2–5 Gy) typically cause temporary redness and hair loss, resolving within 8–40 weeks. 
  • Doses between 5–10 Gy can result in permanent hair loss and skin thickening, with recovery extending beyond 40 weeks. 
  • Very high doses (>15 Gy) may lead to ulcers, peeling, and tissue death, requiring months to years for healing and often necessitating specialized care. These injuries highlight a dose-dependent healing spectrum.^11,12

Why it Matters:

• Nearly 90% of patients receiving radiation therapy experience moderate-to-severe skin reactions, significantly reducing their quality of life and negatively impacting their treatment. The severity is influenced by radiation dose, exposure duration, and individual patient factors including age and skin type.^2,10
• Understanding the timeline of radiation skin injury helps in predicting the course and planning appropriate interventions. Immediate symptoms can often mask more severe underlying damage, requiring vigilance in assessment. 
• Research indicates that timely intervention can significantly reduce morbidity associated with radiation skin injuries.^13,16

Diagnosis:

1. History and Exposure Assessment: Determine the radiation source, dose, and duration of exposure.
2. Physical Examination: Inspect for erythema, blistering, and ulceration. Note the distribution and extent of the injury.
3. Imaging: In severe cases, imaging with ultrasound, CT or MRI may be useful in assessing the extent of tissue injury and in further evaluating other etiologies including infection and worsening malignancy.
4. Biopsy: A biopsy can confirm the extent of cellular damage and rule out alternative diagnoses.¹⁵

Management:

Initial Interventions

1. Cooling and Hydration: Apply cool, moist dressings to the affected area.
2. Pain Control: Administer analgesics as needed.
3. Topical Treatments: topical corticosteroids applied to intact skin may reduce inflammation and pain.¹⁷
4. Infection Prevention: topical antibiotics such as silver sulfadiazene or mupirocin are recommended for open wounds. More severe wounds may warrant systemic antibiotics.¹⁸
5. Mechanical Protection: Apply dressings that minimize pressure and friction on the affected area to prevent aggravation of the injury.¹⁹
6. Psychological Support: Assess and address psychological distress. This may involve offering supportive counseling, referring to mental health services, and providing anxiolytics.²⁰

Advanced Interventions:

• Hyperbaric Oxygen Therapy: Promotes healing in severe, refractory cases.^2,21
• Surgical Intervention: Required for necrotic tissue debridement and severe ulcerations.^9,13
• Several other topical treatments such as Calendula and epidermal growth factor have been studied, but the evidence supporting their use remains limited.^2,17

Radiation-induced skin injuries often cause significant anxiety and depression due to prolonged healing times and visible, distressing symptoms like dryness, itching, and discoloration. Severe cases with functional impairments, such as loss of sweating, further amplify the psychological burden. Emergency medicine providers must recognize this mental health impact and incorporate psychological support into their management plans. Early intervention addressing both physical and mental health needs is essential to improving recovery and quality of life.^25,26

RSI Prevention Strategies:

• Protective Measures: Shielding and limiting exposure time and adhering to radiation dose constraints minimizes risk.^22,23
• Patient Education: Informing patients about skin care during and after radiation treatment.^2,24
• Early Intervention: promptly addressing early symptoms to prevent progression.^13,16

In cases of radiological or nuclear incidents, follow referenced contamination and exposure protocols, including promptly consulting the radiation safety officer, wearing protective equipment, initiating decontamination measures and evaluating for acute radiation syndrome if indicated.¹⁰ REAC/TS, the Radiation Emergency Assistance Center/Training Site, (https://orise.orau.gov/reacts/) is an important resource for information on evaluation, triage, and management of radiation accident exposures. 

Conclusion:

RSI requires a multifaceted approach, from immediate care to long-term monitoring. Emergency physicians can improve patient recovery by recognizing early signs and implementing appropriate initial interventions to mitigate skin injury. Understanding the mechanisms, presentation, and management strategies is crucial for optimizing care in radiation-exposed patients.

Case Follow-up:

The patient underwent a comprehensive wound management regimen, including the removal of necrotic tissue with sodium chloride-soaked cotton balls, application of debridement gel, and use of silver sulfadiazine hydrocolloid dressings. The dressing changes were performed initially every two days and then twice a week as the wound improved. Additionally, the patient received brief psychological intervention during each dressing change, which significantly improved her anxiety and depression scores. Over one month, the wound size reduced from 11 x  12 cm to 1 x 1 cm, with complete epithelialization and resolution of infection. The patient’s HADS scores for anxiety and depression decreased dramatically, and she was able to resume normal social activities with a satisfactory self-image upon discharge.¹

Clinical Pearls:

1. Prompt Recognition: early signs include erythema, dry desquamation, and hair loss. Severe cases can present with moist desquamation, ulceration, and necrosis.
2. Immediate Interventions: initial management focuses on cooling the skin, pain control, and preventing secondary infections.
3. Long-term Monitoring: patients need regular evaluations for late effects, such as fibrosis and secondary cancers.
4. Multidisciplinary Approach: collaboration among various specialists, including wound care experts, oncologists, and mental health professionals, is crucial for holistic patient care and optimizing healing and recovery.
5. Patient Education and Self-care: educating patients on wound care practices and lifestyle modifications, such as wearing soft clothing and avoiding irritants, supports healing and prevents complications.

References:

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3.  Mayo Clinic. Radiation Therapy. Available at: https://www.mayoclinic.org/tests-procedures/radiation-therapy/about/pac-20385162. Accessed July 25, 2024. 2.
4. International Atomic Energy Agency. What is Radiation Therapy? Available at: https://www.iaea.org/topics/radiation-therapy. Accessed July 25, 2024.
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7. Wang Y, Chen S, Bao S, et al. Deciphering the fibrotic process: mechanism of chronic radiation skin injury fibrosis. Front Immunol. 2024;15:1338922. Published 2024 Feb 15. doi:10.3389/fimmu.2024.1338922
8. Kim JH, Kolozsvary AJ, Jenrow KA, Brown SL. Mechanisms of radiation-induced skin injury and implications for future clinical trials. Int J Radiat Biol. 2013;89(5):311-318. doi:10.3109/09553002.2013.765055
9. Shin JY, Yabroff KR, Keegan THM, et al. Trends in Radiation Therapy among Cancer Survivors in the United States, 2000-2030. Cancer Epidemiol Biomarkers Prev. 2017;26(6):963-970. doi:10.1158/1055-9965.EPI-16-1023.
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14. Cleveland Clinic. Epidermis: What Is It, Function & Layers. Cleveland Clinic. Accessed December 7, 2024. https://my.clevelandclinic.org/health/body/21901-epidermis
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17. Backler C, Bruce SD, Suarez L, Ginex PK. Radiodermatitis: Clinical Summary of the ONS Guidelines™ for Cancer Treatment-Related Radiodermatitis. Clin J Oncol Nurs. 2020;24(6):681-684. doi:10.1188/20.CJON.681-684
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21. Bassetto F, Bosco G, Brambullo T, et al. Hyperbaric oxygen therapy in Plastic Surgery practice: case series and literature overview. G Chir. 2019;40(4):257-275. PMID: 31889417.
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