Radiation injury

Radiation injury can be caused by a single whole-body exposure to a high dose of ionizing radiation (acute radiation syndrome; ARS) or single or multiple exposures of a small area of the body to concentrated radiation, e.g., radiotherapy (RT).

ARS is a rare but potentially life-threatening condition caused by unintentional exposure to radioactive material or a nuclear explosion. Initial symptoms are nonspecific and may subsequently coalesce into one or more ARS subsyndromes. Management includes prompt treatment of concomitant injuries, screening for nuclear contamination, assessing the level of ionizing radiation exposure, monitoring for bone marrow suppression and impaired gastrointestinal function, and coordinating multiple specialty consultations (e.g., hematology, gastroenterology, burn specialists).

Radiation injuries following RT are common. Radiation injuries are categorized by the anatomical site of the RT, time elapsed since RT, and patient risk factors. Early adverse effects of RT are caused by radiation-induced proinflammatory states and include radiation pneumonitis and acute radiation proctitis. Late adverse effects are commonly related to fibrosis (radiation fibrosis syndrome), secondary malignancy, and/or tissue ischemia caused by accelerated vascular disease. Management of local radiation injuries is injury specific.

Although radiation injuries to health care providers are rare, providers should be aware of radiation safety recommendations, such as occupational radiological protection and radiological incident protection.

Applied physics ^[1][2]

• Definitions
  • Radiation: energy that moves through space as a particle or wave
    • Nonionizing radiation: low energy radiation that can cause thermal injuries, e.g., infrared, microwave, radio waves
    • Ionizing radiation: radiation capable of ionizing atoms, e.g., x-rays, gamma rays, alpha particles, beta particles
  • Radiation absorbed dose
    • Amount of ionizing radiation deposited in the body per unit mass
    • Measured in gray (Gy) or radiation absorbed dose (rad)
  • Radiation equivalent dose
    • Derivative of the radiation absorbed dose that factors in the potential damage to biological tissue based on the type of radiation
    • Measured in sievert (Sv) or roentgen equivalent man (rem)
• Measurements
  • Geiger counter: a device used to detect the presence of ionizing radiation (e.g., contamination with radioactive material) ^[3]
  • Radiation dosimeter: measures an individual's total accumulated dose of ionizing radiation; typically worn in the form of a badge

The radiation absorbed dose and radiation equivalent dose are equal for medical imaging (e.g., x-rays, CT scans).

Types of radiation injury ^[1][2]

• Irradiation: All or part of the body has been exposed to ionizing radiation, but there has been no transfer of radioactive material to the patient.
• Contamination: Radioactive materials are present on the surface of the body, in a wound, and/or have been ingested.
• Incorporation: Radioactive material has been absorbed into cells and/or tissues following contamination.

Pathophysiology ^[2]

• High doses of ionizing radiation (e.g., radiotherapy, nuclear accidents) can break DNA strands (direct effect) or generate free radicals that cause cellular damage (indirect effect), leading to inflammation and/or progressive tissue damage.
• Cancer cells have an increased susceptibility to radiation because of high replication rates and dysfunctional DNA repair mechanisms.
• Rapidly regenerating tissues (e.g., bone marrow, GI mucosa, skin) have an increased susceptibility to radiation because of the depletion of stem cells.

Radiation safety

Occupational radiological protection ^[4][5][6]

• Keep exposure as low as reasonably achievable (ALARA).
• Wear a radiation dosimeter and avoid exceeding the recommended cumulative exposure.
  • No more than 50 mSv in 1 year ^[4]
  • No more than 20 mSv/year averaged over 5 years ^[4]
  • Pregnancy: < 1 mSv for the entire gestation ^[4]
• Maintain a distance of 2 meters from the radiation source. ^[7]
• Wear a lead apron with ≥ 0.5 mm lead thickness or stay behind an equivalent shield. ^[4]

Radiological incident protection ^[2][8]

• Precautions for patients with ionizing radiation injuries ^[2][8]
  • An ionizing radiation injury without contamination does not pose a risk to providers.
  • Use standard precautions suitable for coexisting injuries.
• Precautions for patients with radioactive contamination ^[2][8]
  • Don PPE that includes isolation gown, surgical mask, protective eyewear or face shield, head cover, and shoe covers.
  • Wear 2 sets of nitrile gloves.
  • Consider N95 or negative pressure respirator with HEPA filter if there is a risk of air dispersion of contaminated material.
  • Frequently test gloves and clothing for contamination using a Geiger counter and replace as indicated. ^[3]

Definition ^[2][9][10]

Acute radiation syndrome (ARS) is a collection of signs and symptoms that occur following whole-body (or significant partial-body) exposure to high-dose ionizing radiation over a short period of time.

Etiology ^[2][3]

• Radiological exposure device
• Radiological dispersal device (“dirty bomb”)
• Nuclear power plant incident
• Nuclear weapon

Clinical features ^{[2][9][10][11]}

The onset and severity of symptoms depend on the level of exposure and type of radiation. ^[3]

• Prodromal
  • Nonspecific symptoms, e.g., anorexia, nausea, vomiting
  • Typical onset: 0–2 days after exposure ^[10]
• Latent
  • Asymptomatic period following resolution of the prodromal phase
  • Typically lasts up to 20 days after exposure ^[9][10]
• Manifest illness
  • Symptoms depend on the severity and location of radiation exposure and typically coalesce into one or more ARS subsyndromes.
  • Typical onset: 21–60 days after exposure

Early symptom manifestation typically suggests significant radiation exposure and a poorer prognosis. ^[3][9][10]

Initial management ^[1][2][3][8]

• Don PPE; see “Radiological incident protection.”
• Perform a primary survey: Do not delay life-saving care to decontaminate the patient.
• Assess for radiation contamination.
  • Obtain medical and incident history.
  • Perform a radioactive contamination assessment.
  • Begin radiation decontamination if necessary.
• Alert radiation experts, e.g.:
  • Hospital radiation safety personnel
  • Poison Control Center: 1-800-222-1222
  • Radiation Emergency Assistance Center: 865-576-1005
• Estimate the level of radiation exposure.
• Begin management of ARS subsyndromes in consultation with radiation experts.

Treat life-threatening emergencies before beginning decontamination; provider exposure to dangerous levels of radiation is highly unlikely. ^[2][3][9]

Treatment of ARS is typically not needed for absorption of < 1 Gy. Survival is unlikely if the absorbed dose is > 10 Gy. ^[10]

Diagnostics ^[1][2][9]

For concomitant traumatic injuries, see “Urgent diagnostics for trauma patients.”

Laboratory studies ^[2][3]

• Initial studies: to establish baseline organ function and assess for acute abnormalities
  • CBC with differential: to determine absolute lymphocyte count
  • Type and screen: Transfusion may be required.
  • Other studies: BMP, LFTs, lipase, CRP, coagulation panel
• Serial studies: to estimate the severity of radiation exposure ^[12]
  • CBC with differential: every 6 hours for 48 hours
  • Serum amylase: daily for 3 days
  • CRP: daily for 3 days

Radioactive contamination assessment ^[8]

• Perform a whole-body radiation scan using a Geiger counter.
• Scan swabs obtained from facial orifices (e.g., nose, mouth) and open wounds. ^[8]
• If internal contamination is suspected, consider scanning 24-hour collections of urine and feces.

Radiation dose estimation ^[9][11]

• Purpose
  • Predicts the likelihood of developing ARS and clinical severity
  • Guides subsequent management, counseling, and disposition decisions
• Methods
  • Time to onset of vomiting
  • Lymphocyte depletion kinetics
  • Dicentric chromosome assay

Radiation decontamination ^{[1][3][8][11]}

• External decontamination
  • Perform body surface decontamination.
  • Protect uncontaminated wounds with waterproof dressings.
  • If necessary and feasible, remove embedded shrapnel.
  • Repeat decontamination up to 2–3 times until surface radiation is less than twice the level of background radiation. ^[3]
  • Follow local biohazard protocols for the collection of water and removed material.
• Internal decontamination ^[2][13]
  • May be initiated under the guidance of radiation experts ^[2][13]
  • Treatment varies based on the radioactive isotope and includes:
    • Iodine-125 or iodine-131: potassium iodide
    • Cesium-137: Prussian blue
    • Plutonium-239 or americium-241: diethylenetriamine pentaacetic acid (DPTA)

ARS subsyndromes ^[2][9][10]

ARS is classically divided into four system-based subsyndromes. Management of ARS subsyndromes requires a multidisciplinary approach tailored to the patient's symptoms. ^[2][13]

Hematopoietic syndrome ^[2][10]

Pancytopenia due to bone marrow damage may occur after absorption of approx. 1 Gy.

• Clinical features
  • Early: neutropenia, signs of thrombocytopenia
  • Late: signs of anemia
• Management may include: ^[14]
  • Neutropenic precautions
  • Antibiotic prophylaxis
  • Management of neutropenic fever
  • Transfusions (e.g., pRBCs, platelet transfusion)
  • Granulocyte colony-stimulating factor
  • Hematopoietic stem cell transplantation (HSCT)

Red blood cells and platelets are radioresistant, since both are terminally differentiated and do not have a nucleus. However, their precursor cells are radiosensitive, resulting in delayed anemia and thrombocytopenia. ^[10]

Gastrointestinal syndrome ^[10]

Prodromal symptoms may occur after absorption of < 1.5 Gy; severe symptoms typically occur after approx. 5–6 Gy.

• Clinical features
  • Prodromal symptoms: nausea, vomiting, gastric atony
  • Severe symptoms: abdominal pain, diarrhea, GI bleeding, signs of significant dehydration
• Management may include:
  • Antiemetics
  • Antidiarrheals
  • IV fluid therapy
  • Nutritional support (e.g., parenteral nutrition)
  • Antibiotic prophylaxis ^[15]

Cutaneous syndrome ^[2]

Symptoms occur after absorption of approx. 3 Gy.

• Clinical features
  • Early: erythema, edema, hair loss
  • Late: desquamation, ulceration, necrosis ^[10][13]
• Management may include: ^[15][16]
  • Topical steroids
  • Topical antibiotics
  • Burn management
  • Referral to a burn center

Neurovascular syndrome ^[2][10]

Symptoms occur after absorption of approx. 10–20 Gy ; neurovascular syndrome and is universally fatal.

• Clinical features
  • Altered mental status (e.g., confusion, disorientation, decreased level of consciousness)
  • Headaches
  • Seizures
  • Ataxia
  • Papilledema
• Management may include: ^[15]
  • Palliative care
  • Antiepileptics

Disposition ^[10][13]

• Disposition decisions should be made in consultation with radiation experts and include the following factors:
  • Severity of symptoms
  • Radiation exposure
  • Community contamination risk
• Consider transfer to specialized centers as indicated (e.g., trauma center, burn center, HSCT center).

Local radiation injuries typically result from radiation therapy (RT) administered in high doses (e.g., 40–80 Gy) to a small area of the body as opposed to whole-body radiation that causes ARS.

Overview ^[17][18][19]

• The pathophysiology and treatment of local radiation injuries varies by the type, dose, and location of RT.
• Local radiation injuries are classified as early (occurring within weeks of RT) or late (occurring months to years after RT). ^[17]
  • Early injuries are typically caused by a proinflammatory state leading to organ dysfunction.
  • Late injuries are often related to radiation-induced fibrosis (radiation fibrosis syndrome), secondary malignancy, and/or accelerated vascular disease.

Local radiation injuries by location of radiation therapy

Radiation-induced lung injury (RILI) is a complication of thoracic RT, which is commonly used in the treatment of lung cancer, mediastinal lymphoma, and breast cancer. RILI may manifest acutely as radiation pneumonitis or later as radiation-induced pulmonary fibrosis. ^[27]

Radiation pneumonitis ^[27][28]

• Definition: acute or subacute lung tissue inflammation caused by RT
• Onset: within 3–12 weeks of radiation. ^[27]
• Mechanism of injury: rapid release of proinflammatory cytokines (e.g., IL-1, IL-6) from alveolar cells, resulting in a proliferative reaction that impairs gas exchange
• Clinical features
  • Most common: dyspnea, dry cough
  • Less common: hemoptysis, fever, asymptomatic
• Diagnostics
  • Clinical diagnosis after ruling out alternative diagnoses (e.g., pneumonia, pulmonary embolism) ^[28]
  • CXR and CT chest findings vary by phase of injury from normal to ground glass opacities.
• Management: systemic corticosteroids
• Complications
  • Respiratory insufficiency
  • Radiation-induced pulmonary fibrosis

Radiation-induced pulmonary fibrosis ^[28]

• Definition: chronic pulmonary tissue damage caused by sclerotic fibrosis ^[27][29]
• Onset: typically 6–12 months after RT ^[19]
• Clinical features: progressive dyspnea, tachypnea, cyanosis
• Diagnostics
  • CT chest is preferred to CXR
  • CT findings include linear scarring with consolidation and volume loss. ^[28]
• Management: supportive care, e.g., oxygen therapy, pulmonary rehabilitation

Always rule out infection, thrombotic events, and/or cancer recurrence before diagnosing radiation-induced lung injury in patients with a history of thoracic RT. ^[28]

Radiation-induced esophagitis ^[30]

• Onset: most commonly 2–3 weeks after initiation of RT initiated
• Clinical features
  • Early: dysphagia, odynophagia, anorexia, nausea, substernal discomfort
  • Late: mechanical dysphagia, impaired esophageal motility
• Diagnostics
  • Clinical diagnosis
  • Endoscopy is used to differentiate radiation injury from infectious esophagitis.
• Management
  • Dietary modifications (e.g., soft, bland diet)
  • Symptomatic management
    • Topical analgesics (e.g., oral viscous lidocaine)
    • Antacids and acid suppressor medications (e.g., PPI, H2 blockers)
• Complications: esophageal stricture, esophageal perforation, tracheoesophageal fistula

Radiation enteritis ^[31][32]

RT for abdominopelvic malignancy frequently causes proinflammatory injuries to both the small and large bowel.

Acute radiation enteritis ^[31][32]

Acute radiation enterocolitis is common but often self-limited. Diagnostics and management vary with the severity of the symptoms.

• Onset: hours to weeks after RT
• Incidence: 80% of patients receiving abdominopelvic RT ^[32]
• Clinical features: nausea, vomiting, diarrhea, abdominal pain, weight loss
• Diagnostics
  • Clinical diagnosis
  • Consider additional studies based on symptoms:
    • Diarrhea: stool diagnostic studies
    • Severe abdominal pain or weight loss: CT abdomen and pelvis
• Management: supportive care
  • Antidiarrheal therapy, e.g., bulking agents, antimotility agents
  • Antiemetic therapy
  • Treatment of dehydration
  • Discontinuation of RT if symptoms are severe

Chronic radiation enteritis ^[31][32]

• Onset: months to years after RT
• Incidence: 20% of patients receiving abdominopelvic RT ^[32]
• Clinical features: diarrhea, malabsorption, ulcerations, strictures, fistulas, bowel obstruction, perforation
• Diagnostics
  • Imaging, e.g., CT enterography, MRI enterography
  • Endoscopy, e.g., EGD, colonoscopy
• Management ^[31][32]
  • Medical management
    • Malnutrition: specialized nutrition support
    • Diarrhea: antidiarrheal therapy
    • Small bowel strictures: low residual diet
    • Bile acid malabsorption: bile acid sequestrants
    • Small bowel bacterial overgrowth: antibiotic therapy
  • Surgical management ^[31]
    • Resection of strictures to relieve bowel obstruction
    • Repair fistulas and/or perforations.

Radiation proctitis ^[33][34][35]

Radiation proctitis is a common complication of pelvic RT for anal, prostate, rectal, cervical, and/or bladder cancer.

Risk factors ^[33][34]

• Therapy-associated risk factors: total area irradiated, dose of radiation, type of radiation ^[33]
• Patient-associated risk factors
  • Diabetes, ASCVD, smoking
  • Inflammatory bowel disease ^[31][36]
  • HIV, immunocompromised individuals (limited evidence) ^[36]

Acute radiation proctitis ^[33][34][36]

• Onset: 0–3 months after RT ^[34]
• Incidence: up to 75% of patients undergoing pelvic radiation ^[34]
• Pathophysiology: radiation therapy → acute mucosal inflammation ^[31]
• Clinical features
  • Rectal pain, diarrhea, tenesmus
  • Mucus discharge, minor bleeding
• Diagnostics: endoscopy, possibly with biopsy ^[33][34]
  • Endoscopic findings: ulcerations, deep-red edematous mucosa
  • Histopathology findings: edema, ulceration, hyperemia, loss of microvillus architecture
• Management: supportive care
  • Antidiarrheal therapy
  • Treatment of dehydration
  • 5-ASA and/or steroid enemas
  • Discontinuation of RT if symptoms are severe

Chronic radiation proctitis ^[34][36][37]

• Onset: 3 months to years after RT ^[36]
• Incidence: 2–20% of patients undergoing pelvic radiation ^[34]
• Pathophysiology: radiation causes damage to blood vessels → compromised blood flow to the rectal wall → fibrotic changes and ischemia ^[33][34][36]
• Clinical features ^[33][36]
  • Clinical features of acute radiation proctitis
  • Bowel strictures, fistulas, obstruction, perforation
  • Bleeding (potentially life-threatening)
• Diagnostics: endoscopy with biopsy
  • Endoscopic findings ^[36]
    • Pale mucosa, telangiectasias
    • Strictures, ulcerations, fistulas
    • Heavy bleeding
  • Histopathology findings: damaged small arteries and arterioles showing signs of intimal fibrosis
• Management ^[37]
  • Medical management
    • Topical formaldehyde
    • Sucralfate enemas
  • Interventional management
    • Endoscopic therapy, e.g., argon plasma coagulation
    • Hyperbaric oxygen therapy
    • Surgery, e.g., resection, colonic diversion

Acute radiation cystitis ^[38]

• Clinical features: dysuria, urinary frequency, urinary urgency
• Diagnostics: urinalysis and/or urine culture to rule out UTI
• Management
  • Analgesia, e.g., phenazopyridine
  • Anticholinergics, e.g., oxybutynin

Radiation-induced hemorrhagic cystitis ^[35][38]

• Clinical features
  • Mild to life-threatening hematuria
  • Urinary retention from clot formation
  • Signs of anemia
• Diagnostics
  • Urinalysis and/or urine culture to rule out UTI
  • Severe hemorrhagic cystitis: CBC, coagulation panel, type and screen
  • See also “Approach to hematuria” for workup of gross hematuria.
• Management
  • Mild hemorrhagic cystitis: referral to urology for further evaluation of hematuria
  • Severe hemorrhagic cystitis
    • Manage hemorrhagic shock (e.g., fluid resuscitation, transfusion).
    • Insert Foley catheter and initiate intermittent or continuous bladder irrigation.
    • Consult urology for further management.

Life-threatening hematuria occurs in 5–8% of patients after pelvic RT. ^[35]

Approximately 95% of patients undergoing radiotherapy develop radiation dermatitis. ^[39]

Acute radiation dermatitis ^[17][20][40]

For cutaneous effects of acute radiation syndrome, see “Cutaneous syndrome” in “ARS subsyndromes.”

• Onset: within 90 days of radiotherapy ^[39]
• Risk factors ^[40]
  • Intrinsic: e.g., older age, female sex, obesity, diabetes mellitus, immunocompromised state, current smoker
  • Extrinsic: e.g., concurrent chemotherapy, higher radiation doses
• Clinical features: dose-dependent; most common in moist intertriginous areas
  • Mild features: develop within 1–4 weeks
    • Erythema
    • Pruritus
    • Dry desquamation
    • Depigmentation
    • Scaling
  • Severe features: develop after ∼ 4–6 weeks
    • Moist desquamation
    • Ulceration
    • Hemorrhage
    • Skin necrosis
• Diagnostics: clinical diagnosis
• Management
  • Mild dermatitis: moisturizers, low or medium-potency topical steroids ^[39][40]
  • Severe dermatitis: dressings, debridement, skin grafts
• Complications
  • Skin infection
  • Chronic wounds
  • Fibrosis

The use of certain medications (especially chemotherapy agents) following radiotherapy may cause radiation recall dermatitis, in which symptoms of acute radiation dermatitis develop weeks to months after radiotherapy. ^[40]

Chronic radiation dermatitis ^[40][41]

• Onset: > 90 days after radiotherapy ^[41]
• Clinical features
  • Atrophy and skin breakdown
  • Pigmentation changes
  • Telangiectasias
  • Fibrosis and induration
  • Second malignancies (nonmelanoma skin cancers)
• Diagnostics
  • Diagnosis is usually clinical.
  • Diagnostic uncertainty:
    • Obtain biopsy.
    • In patients with history of breast cancer, also obtain an MRI to exclude tumor recurrence. ^[40]
• Management: based on clinical features
  • Ulcers: wound care ^[40]
  • Telangiectasias: laser therapy
  • Fibrosis
    • Physical therapy to improve range of motion
    • Analgesia
    • Oral pentoxifylline +/- tocopherol
    • Laser therapy
  • Malignancies: See “Treatment of BCC” and “Treatment of cSCC.”
• Complications
  • Contractures
  • Chronic pain
  • Wound infection

Prevention of radiation dermatitis ^[40]

• Gentle cleansing with mild soap and lukewarm water
• Unscented, water-based moisturizer
• Photoprotective measures
• Loose-fitting clothes
• Low- or medium-potency topical steroids may be considered. ^[39][40]

Radiation to the brain (affecting pituitary hormones) or pelvis may also affect fertility; for preventive measures, see “Managing fertility during anticancer therapy.” For patients already experiencing infertility, diagnostics and treatment of infertility are the same as for patients who have not undergone radiotherapy.

Erectile dysfunction ^[20][42]

• Onset: 1–3 years after radiotherapy ^[42]
• Diagnostics: See “Diagnostics for erectile dysfunction.”
• Management
  • Optimize management of concurrent conditions associated with sexual dysfunction. ^[42]
  • Offer referral for counseling. ^[43]
  • Treatment of erectile dysfunction is the same as for patients who have not undergone radiotherapy. ^[43]

Sexual dysfunction in women ^[20][44][45]

• Onset
  • Acute effects occur shortly after radiotherapy and resolve in 2–3 months. ^[45]
  • Stenosis and atrophy occur months to years after radiotherapy.
• Clinical features
  • Acute effects include vaginal erythema, mucositis, and desquamation.
  • Long-term effects include:
    • Atrophy and stenosis of the vagina and vulva → vaginal dryness, dyspareunia
    • Low libido
    • Anorgasmia
• Diagnostics: clinical diagnosis
• Management ^[43]
  • All patients: Offer referral for counseling.
  • Suspected pelvic floor dysfunction: Refer to pelvic floor physical therapy.
  • For symptoms of atrophy and stenosis, recommend:
    • Vaginal lubricating gel during sexual activity
    • Moisturizer applied to the vagina and vulva 3–5 times per week ^[43]
    • Vaginal dilators
  • Consider additional treatments in consultation with a specialist. ^[43][46]
• Prevention: Postradiotherapy use of vaginal dilators may prevent stenosis. ^[47][48]