Clinical manifestations, evaluation, and diagnosis of acute radiation exposure

INTRODUCTION — Radiation affects functions of cells, tissues, organs, and the whole person. A basic knowledge of radiation physics is necessary for understanding the clinical manifestations of radiation exposure and injury.

This topic will address the clinical manifestations, evaluation, and diagnosis of acute radiation injury.

Evaluation and management of radiation injury and radiation therapy techniques are discussed separately. (See "Management of radiation injury" and "Radiation therapy techniques in cancer treatment".)

RADIATION PHYSICS — Radiation is the transfer of energy through space as high-speed particles and/or electromagnetic waves. Radiation can be ionizing or nonionizing.

Ionizing radiation — Ionizing radiation has sufficient energy to displace electrons, thereby creating charged particles (eg, ions). It is released by unstable atoms that have an excess of energy, mass, or both, which emit the excess energy to become stable. Ionizing radiation has very short wavelengths, ranging from nanometers to a million millionth of a meter (10^-12). It includes higher frequency ultraviolet (UV) radiation, X-rays, gamma rays, and particulate ionizing radiation (eg, alpha particles, beta particles, neutrons).

●Alpha particles – Alpha particles are helium nuclei (ie, two protons and two neutrons) that have been stripped of their electrons; they have an atomic mass of four daltons (Da). Alpha particles do not penetrate clothing, skin, or paper, but they are harmful when ingested or inhaled. Radionuclides that emit alpha particles include polonium-210, radon-222, radium-226, thorium-232, plutonium-236, uranium-238, and americium-241 (table 1).

●Beta particles – Beta particles are electrons with an electrical charge of –1 and an atomic mass of 1/2000^th that of a proton or neutron. Beta particles can penetrate into subcutaneous tissues but are blocked by wood or brick. They are particularly harmful when ingested or inhaled. Examples of beta emitters include tritium, cobalt-60, strontium-90, technetium-99, iodine-129, iodine-131, and cesium-137.

●Neutrons – Neutrons are particles that have a mass of one Da, but they are electrically neutral, which permits deep penetration into tissue. Neutrons are emitted only after a nuclear detonation.

●Protons – Protons are a component of all nuclei, which have an electrical charge of +1 and a mass of one Da; the number of nuclear protons is equivalent to the atomic number of an atom. Due to their high mass (ie, nearly 2000 times greater than the mass of an electron), they require complex equipment (such as a cyclotron) to accelerate them to energies that are useful for the treatment of cancer.

●X-rays and gamma rays – X-rays and gamma rays are pure electromagnetic energy that is measured as photons, and they have no mass or electrical charge. They penetrate tissues and expose all organs but are blocked by a concrete wall. X-rays generally have a longer wavelength than gamma rays, but there is no common definition that distinguishes X-rays from gamma rays. X-rays are generally emitted by electrons rather than the atomic nucleus, whereas gamma rays may be released from the nucleus.

Ionizing radiation displaces electrons from multiple orbits, creating unstable atoms (eg, radionuclides); this contrasts with chemical reactions, in which electrons are removed from the outermost orbits of an atom. As the radionuclide emits energy (ie, disintegrates), it transforms into a different isotope of the same element through a process known as radioactive decay. Decay products are often radioactive and achieve stability after subsequent decays, releasing energy as particles or rays at each step. Such decay chains are characteristic for a radionuclide.

Clinical effects of ionizing radiation are discussed below. (See 'Clinical manifestations' below.)

Nonionizing radiation — Nonionizing radiation has enough energy to move or vibrate atoms, but it lacks the energy to displace electrons from their orbit. Nonionizing radiation has long or very long wavelengths, ranging from a fraction of a micrometer to millions of meters, and includes radio waves, microwaves, infrared light, and the visible portion of the electromagnetic spectrum into the UV light range.

Nonionizing radiation does not penetrate human tissue, poses no risk of contamination, and is easily shielded by sunscreens, sunglasses, and clothing. Nonionizing radiation causes damage to cells through direct transfer of thermal energy. Sunburn is a classic example, but nonionizing radiation can also cause corneal or retinal burns and microwaves can produce heating of tissues. Clinical effects of nonionizing radiation are discussed separately. (See "Sunburn", section on 'Clinical manifestations'.)

Measures of radiation — Radiation can be expressed as activity and absorbed radiation in biologic tissues (table 2):

●Activity – Activity refers to the number of atomic disintegrations per unit time. A becquerel (Bq), a measure in the Système International (SI), is equal to the amount of material that is undergoing 1 disintegration/second (dps). Bq has superseded the term curie (Ci), which is the amount of radioactive material undergoing 3.7 x 10¹⁰ dps; 1 mCi equals 37 MBq.

●Dose rate – Dose rate refers to the amount of radiation delivered per unit time. A gray (Gy) is defined as the absorption of one joule/kg in the SI. The SI term Gy has superseded the radiation absorbed dose (rad); 1 Gy is equal to 100 rad.

●Dose equivalent – Dose equivalent represents the product of the absorbed dose rate and a weighting factor that reflects the relative biologic effectiveness (rbe) of various sources of ionizing radiation on tissues. As examples, the rbe of X-rays and gamma rays is 1, while the rbe for alpha particles is 20. The SI term sievert (Sv) has superseded the roentgen equivalent in man (rem); 1 Sv is equal to 100 rem.

SOURCES OF RADIATION EXPOSURE — Radiation exposure may result from background radiation, medical exposure, industrial exposure, and accidental or deliberate nuclear events (eg, nuclear reactor incidents, detonation of nuclear weapons, or terrorist activity with intentional release of radioactive material [eg, dirty bomb]). Radiation exposure is increasing in the general population, primarily due to heightened use of medical imaging. The risk of radiation exposure attributable to imaging is discussed separately. (See "Radiation-related risks of imaging".)

Background radiation arises from numerous sources, including cosmic radiation, terrestrial radiation (eg, radon decay products from earth and construction materials), and endogenous sources (eg, potassium-40). Examples include [1]:

●Natural background radiation: 3 mSv/year

●Round-trip intercontinental air flight: 0.02 to 0.03 mSv

●Living in a brick house: 0.0002 mSv/year

BIOLOGIC EFFECTS OF RADIATION — Biologic effects of radiation depend on the type and amount of radiation exposure and the tissues that are exposed:

●Radiation exposure – Different types of ionizing radiation exposure produce distinctive patterns of injury:

•Alpha particles can cause superficial skin damage

•Beta particles cause local injury (usually burns), but can cause tissue damage if ingested or inhaled

•Neutrons cause tissue damage

•X-ray or gamma radiation causes both local injury and acute radiation syndrome

Effects on the whole person are also influenced by the dose, schedule, and route of exposure; volume of exposed tissue (ie, partial-body versus whole-body); and shielding. The lethality of ionizing radiation varies with the dose rate (ie, doses received over a shorter period of time cause more damage), distance from the source (the dose rate decreases as the square of the distance from the source; the inverse square law), and shielding [2]. As examples, alpha particles can be stopped by a sheet of paper or a layer of skin, beta particles by less than one inch of plastic, and gamma rays by inches to feet of concrete or an inch of lead. Exposure to ionizing radiation can be reduced by minimizing the time of exposure, maximizing the distance to the source, and with shielding.

Vulnerability to radiation exposure varies between individuals, but the mechanisms that account for differential radiation sensitivity are largely undefined [3,4]. However, infants and young children as well as patients with certain genetic syndromes (eg, Fanconi anemia) that impair DNA-damage responses are more vulnerable to radiation injury. (See "Clinical manifestations and diagnosis of Fanconi anemia".)

●Lethal dose – Lethality of radiation varies with the type of radiation, degree of exposure, and access to medical care. Lethality is expressed as the LD50: the median radiation dose at which 50 percent of exposed patients die within 30 days. The LD50 for energetic, penetrating gamma rays is estimated to be 4.5 Gy [5]. However, it is important to recognize that considerably higher doses of radiation are tolerated with therapeutic irradiation (eg, doses ≥12 Gy for treatment of malignancies) than with unintentional exposures, in which shielding is random.

Unshielded exposure to ≥10 Gy is uniformly lethal within six months [6,7]. A comprehensive review of individuals who were accidentally exposed to ionizing radiation and who received contemporary supportive care, including cytokine therapy, indicated that virtually all persons exposed to ≥5 to 6 Gy died within one year after exposure [8]. Lethality also varies with access to medical care. For patients who have rapid access to surgical and burn intensive care units, reverse isolation wards, and bone marrow transplantation, the LD50 can rise to 10 Gy; with access to blood transfusions and antibiotics, the LD50 is 4.5 Gy; whereas for patients who have access only to basic first aid, the LD50 is 2.5 Gy [9]. (See "Management of radiation injury".)

●Tissue exposure – Biologic effects of radiation depend on the types of exposed tissues. Short-lived cells are more vulnerable to radiation-induced triggering of apoptosis or necrosis and inhibition of cell renewal. Highly proliferative cells, such as spermatocytes, hematopoietic precursors, circulating lymphocytes, and intestinal crypt cells are among the most critically affected cell types. As examples, the threshold doses for testis (0.15 Gy) and bone marrow (0.5 Gy) are lower than those for other organs.

Ionizing radiation has dose-dependent ("deterministic") effects with predictable thresholds for tissue reaction and severity of injury (eg, bone marrow suppression). Radiation also has a random ("stochastic") effect, whereby the dose affects the probability of an effect rather than severity of injury. Stochastic effects do not have an apparent threshold dose, which implies that any dose, no matter how low, can have an effect. An example of a stochastic effect is radiation-induced carcinogenesis, which has a generally long but variable time from exposure to effect.

Ionizing radiation can damage macromolecules (eg, DNA, RNA, proteins) and cellular components (eg, plasma membrane). Radiation effects can be direct (eg, single- or double-strand DNA breaks) or indirect (by interacting with water or other molecules to produce free radicals). The chance of damage to a cellular target varies with the amount of ionization created along the track of radiation. Sources of radiation with low linear energy transfer (LET), such as X-rays and gamma rays, produce sparse ionization, while high LET radiation sources, such as alpha particles and neutrons, cause dense ionization.

TYPES OF RADIATION EXPOSURE — Various types of radiation exposure may occur, either alone or simultaneously.

Irradiation — Irradiation occurs when an individual is exposed to penetrating radiation from an external source. The radiation may pass through the body or be absorbed by it. Irradiated individuals are not radioactive (ie, do not emit radiation) and they pose no risk to others, as long as they are not also contaminated with radioactive particulate matter.

Effects of radiation are influenced by whether the patient received whole-body versus partial-body irradiation [10]. Whole-body exposure occurs when the entire body surface area is exposed to penetrating ionizing radiation. Manifestations of whole-body irradiation as acute radiation syndrome are described below. (See 'Acute radiation syndrome' below.)

Partial-body (or local) radiation exposures involve irradiation of a part of the body, which results in local radiation injury (eg, to skin, gonads, eyes), as discussed below. (See 'Partial exposure' below.)

Internal contamination — Internal contamination occurs when radioactive particles are incorporated into cells, tissues, and organs through ingestion, inhalation, or absorption through open wounds or mucosal surfaces [11-13]. Internal contamination is difficult to eliminate due to binding of radionuclides to human tissues (eg, bone, liver, lungs). Internal contamination is especially dangerous for children, who have a greater risk for cancer development due to longer life span, more rapid growth rate, and higher cell turnover than adults [12].

External contamination — External contamination occurs when radioactive substances such as dust, particulate matter, or liquids adhere to the patient's skin, hair, or nails. External contamination with alpha or beta particles can be detected through monitoring with alpha detectors and Geiger counters [14,15]. External contamination rarely causes significant clinical effects, unless accompanied by a puncture wound or severe burn through which radionuclides may be internalized, but it poses a risk to medical providers that should be recognized and mitigated.

Perceived — Perceived radiation injury, fear that is out of proportion to the actual danger, is most common and is fostered by misconceptions about the health effects of radiation [12,16,17]. Anxiety is increased because exposure to ionizing radiation cannot be felt, heard, or seen, the onset of symptoms is delayed, and children are most susceptible to the potential long-term effects (malignancy, intellectual disability, physical disability, and germ cell mutation) [18]. The emotional stress and anxiety caused by perceived radiation exposure may cause nausea, vomiting, and/or diarrhea that can make perceived exposure difficult to differentiate from irradiation or contamination [19].

RECOGNITION — Radiation injury is most likely to be recognized because of an individual's proximity to a known exposure incident; this exposure may or may not be accompanied by a public announcement, indication of exposure from a monitoring device, clinical symptoms, or laboratory findings soon after the event. Radiation exposure and/or contamination is most common in individuals who work with radioactive material, such as radiologic equipment or medical waste disposal. However, a passer-by or an individual who inadvertently handles such a source may also be exposed to radiation with or without contamination. For others, radiation injury may result from proximity to or being downwind of a known radiation incident (eg, nuclear power plant release, core melt-down, or nuclear explosion).

Recognition of a radiation incident may also be triggered by unexplained clinical and/or laboratory findings in an individual or a cluster of people that are consistent with acute radiation injury and/or multiorgan dysfunction. However, recognition of radiation injury under these circumstances requires a high degree of suspicion and awareness of the clinical features of radiation injury. (See 'Clinical manifestations' below.)

When a radiologic event is announced publicly or a patient with suspected radiation injury has arrived to the facility, hospital personnel should activate the facility's emergency medical response plan and obtain the necessary inhouse radiation safety personnel (ie, staff from Nuclear Medicine, Radiation Oncology, Radiology, and Radiation Safety) or obtain expert consultation through a regional poison control center (in the United States, call 1-800-222-1222 to be connected to the nearest poison control center; contact information for poison centers around the world is provided separately (see 'Additional resources' below)) or the Radiation Emergency Assistance Center and Training Site (REAC/TS) at Oak Ridge, Tennessee (after-hours phone number: 865-576-1005; general information phone number: 865-576-3131). (See "Management of radiation injury", section on 'Approach'.)

CLINICAL MANIFESTATIONS

Acute radiation syndrome — Acute radiation syndrome (ARS) occurs hours, days, or weeks after whole-body exposure (or large partial-body exposure) to sufficient penetrating radiation to cause clinically apparent injury [20]. Initial clinical features are nonspecific (table 3) and vary according to the degree and type of radiation exposure. Most commonly, ARS is manifest as cutaneous, gastrointestinal, hematologic, and/or neurologic findings.

In the absence of a known exposure, recognition of acute radiation injury requires a high degree of suspicion based on clinical findings and/or laboratory evaluation.

Magnitude of exposure — The signs and symptoms of ARS are related to the type of radiation and the absorbed dose of radiation.

The threshold whole-body dose for ARS in adults is approximately 1 Gy (100 rad); lower doses are not expected to cause clinically apparent ARS. A whole-body dose of 4.5 Gy is lethal to 50 percent of exposed persons (LD50) and a dose of ≥10 Gy is typically associated with 100 percent mortality [20]. All forms of ionizing radiation can cause internal tissue damage after ingestion, inhalation, or transfer through a wound. X-rays, gamma rays, and neutrons penetrate the skin and can cause deep tissue injury after either external exposure or contamination. By contrast, external exposure to high energy beta particles (without ingestion or inhalation) can cause serious skin damage but does not cause deep tissue injury, unless they are of high energy and are delivered at a high dose. Alpha particles are blocked by clothing and intact skin and are typically harmful only when they are internalized via a wound, abrasion, ingestion after transfer from the hands to foodstuffs, or inhalation. Effects of radiation exposure also vary with the dose rate of radiation, shielding, and availability of medical care. (See 'Biologic effects of radiation' above.)

The threshold dose for radiation injury is lower in children, as discussed below. (See 'Pediatric considerations' below.)

Time course of ARS — ARS progresses through three phases, and the onset, duration of the phases, and dominant manifestations of the syndrome depend on the dose of radiation (table 3) [14,16,20]:

●Prodromal phase (0 to 2 days after exposure) – The prodromal phase refers to early symptoms or signs, which are generally nonspecific. At doses between 1 and 2 Gy, a prodrome that may include anorexia, nausea, vomiting, fatigue, tachycardia, fever, and/or headache becomes evident [15,21]. Early onset (eg, <2 hours after exposure) and persistence of nausea, vomiting, and/or diarrhea indicates a severe radiation exposure.

●Latent phase (2 to 20 days after exposure) – The latent phase is a period of improvement in prodromal symptoms. The duration of the latent phase is inversely related to the dose of radiation received, and patients with severe, lethal exposure may progress directly from prodromal phase to manifest illness.

●Manifest ARS (21 to 60 days after exposure) – Manifest ARS follows a predictable pattern that generally begins with infection, anemia, and bleeding; followed by uncontrollable diarrhea, hypovolemia, and electrolyte disturbances; and finally, deteriorating mental status, cerebral edema, and overwhelming cardiovascular collapse [6].

●Recovery phase – The recovery phase refers to the period after manifest ARS where the patient recovers from the acute exposure. The timing for recovery will depend on the severity of injury and affected organ system(s).

Even after recovery from acute radiation injury, the patient remains at risk for chronic injury and long-term complications, such as myelodysplastic syndrome, various leukemias, solid tumors (eg, cancer of the thyroid, breast, and brain), and thyroid disease. Long-term effects are similar to those after therapeutic radiation. (See "Approach to the adult survivor of classic Hodgkin lymphoma", section on 'Radiation therapy' and "Overview of Hodgkin lymphoma in children and adolescents", section on 'Late complications' and "Second malignancies after treatment of classic Hodgkin lymphoma".)

ARS subsyndromes — The four prominent subsyndromes of ARS, which may occur individually or in combination, are cutaneous (table 4), hematopoietic (table 5), gastrointestinal (table 6), and neurovascular (table 7) [10]. Although there are characteristic patterns of injury for each subsyndrome, the severity and time course may vary in a given individual based on the specific exposure.

Cutaneous — Cutaneous manifestations of ARS vary with the nature of the exposure (ie, the types of ionizing particles and/or rays), dose, and interval since the exposure. (See 'Ionizing radiation' above.)

Radiation effects of ionizing radiation on skin are dose-dependent [22,23]:

●≥3 Gy (300 rad) – Hair loss

●≥6 Gy – Erythema

●>10 Gy – Dry desquamation

●>15 Gy – Moist desquamation

●>20 Gy – Necrosis

The time between exposure and clinical manifestations varies inversely with the dose of radiation (ie, skin findings are seen sooner with a higher dose) (table 4) [12]. Cutaneous effects usually begin with a prodrome of transient erythema within hours of exposure that may progress to intense burning or tingling, followed by a symptom-free interval of days to weeks [15,22]. Secondary erythema usually develops in 5 to 21 days, but it may appear earlier with more significant exposure. For severe exposure, initial erythema may be followed by intense reddening, blistering, and ulceration that can proceed to necrosis of the exposed region. Very large skin doses may cause permanent hair loss, damage to sebaceous and sweat glands, atrophy, fibrosis, keloids, changes in skin pigmentation, and progressive fibrosis of the vasculature that may take months or years to fully evolve [24].

Effects also vary with the type of the radiation. High energy beta particles (as in the Chernobyl event) cause early moist desquamation with subsequent healing, but within two months full thickness loss of exposed skin can occur due to collapse of the dermal vascular system [24,25]. Many long-term survivors from the Chernobyl incident required amputation for persistent ulcers and significant fibrosis [2].

Management of cutaneous radiation injury is discussed separately. (See "Management of radiation injury", section on 'Cutaneous syndrome'.)

Hematopoietic — Ionizing radiation has predictable dose- and time-dependent effects on hematopoiesis that are manifest as cytopenias (ie, neutropenia, lymphopenia, anemia, and thrombocytopenia) with resultant clinical consequences, including infections, weakness, and bleeding (table 5). The fall in lymphocyte count is dose-related, and sequential lymphocyte counts can be used to approximate the radiation dose (table 8) and prognosis, as discussed separately. (See 'Evaluation' below.)

Clinical manifestations of radiation-induced hematopoietic toxicity become apparent at doses >2 to 4 Gy (200 to 400 rad), but recovery may occur if bone marrow stem and progenitor cells are not completely eradicated [12,25]. The earliest hematologic effect is a fall in the absolute lymphocyte count, which begins in the first hours after exposure and continues for several weeks before returning to baseline [21]. Neutrophils, platelets, and red blood cells are affected subsequently: Neutropenia reaches a nadir at two to four weeks, when life-threatening infections can occur [6,14,15,18,26]. Thrombocytopenia also occurs at this time and can persist for several months. Anemia develops from gastrointestinal blood loss, hemorrhage into organs and tissues, and bone marrow aplasia. Radiation can also have long-term consequences for immune function and is associated with the development of various myeloid malignancies (eg, myelodysplastic syndromes, chronic myeloid leukemia, or acute myeloid leukemia). (See "Genetic abnormalities in hematologic and lymphoid malignancies".)

Management of the hematopoietic effects of ARS is discussed separately. (See "Management of radiation injury", section on 'Hematopoietic syndrome'.)

Gastrointestinal — Gastrointestinal (GI) manifestations (table 6) of ARS vary with the dose and time from exposure to radiation. The occurrence and timing of vomiting can be used with the absolute lymphocyte count to determine the dose of radiation exposure (table 8). The GI tract is vulnerable to radiation injury from damage to the mucosal barrier, loss of proliferative epithelial cells in the intestinal crypts, and effects on the vasculature.

At doses as low as 1.5 Gy (150 rad), a prodromal syndrome of nausea, vomiting, and anorexia may be observed. Exposure to higher doses leads to more severe and/or persistent GI manifestations within five days of initial exposure [26,27]. At doses >5 Gy, nausea, vomiting, and bloody diarrhea accompanied by malabsorption, massive fluid losses, hypovolemia, and cardiovascular collapse occur [22]. The risk of death from sepsis is increased by disruption of the mucosal barrier coupled with the depleted immune system, and GI bleeding is exacerbated by thrombocytopenia. (See "Hypovolemic shock in children in resource-abundant settings: Initial evaluation and management" and "Sepsis in children: Definitions, epidemiology, clinical manifestations, and diagnosis".)

Management of the GI effects of ARS is discussed separately. (See "Management of radiation injury", section on 'Gastrointestinal syndrome'.)

Neurovascular syndrome — Manifestations of ionizing radiation on the central nervous system (CNS), called neurovascular syndrome, vary with the dose and time from exposure and range from nonspecific findings to severe cognitive and neurologic effects (table 7).

CNS effects of radiation may begin as nausea, vomiting, and lethargy within minutes of exposure. With a lethal dose of radiation (ie, >10 Gy), a latent period lasting several hours is followed by severe incapacitation that progresses to coma and death within 24 to 48 hours [22]. Disorientation, ataxia, prostration, seizures, fever, and hypotension occurring within 24 to 48 hours are also predictive of a lethal exposure. Autopsy reveals that these patients have focal hemorrhages with necrosis, white matter edema, demyelination, and significant microvascular damage [6,15,21].

Management of CNS manifestations of ARS is described separately. (See "Management of radiation injury", section on 'Central nervous system syndrome'.)

Partial exposure — The skin, gonad, and eyes are at greatest risk for radiation damage in a patient with partial-body exposure:

●Skin – Partial-body exposure causes cutaneous effects in the exposed regions of skin. A patient with partial cutaneous radiation injury may present with a blistering skin lesion but no history of a chemical or thermal burn, insect bite, or known skin disease or allergy. Supportive history may also include employment in a field where radiation is used, handling of an unknown metal object, exposure to an unknown powder or liquid, or proximity to a cluster of patients with similar skin findings [11]. Partial radiation exposures often involve the hand or skin adjacent to a clothing pocket (eg, thigh).

Dose-dependent manifestations of cutaneous acute radiation injury (table 4) are described above. (See 'Cutaneous' above.)

Exposure of skin to nonionizing radiation is discussed separately. (See "Sunburn", section on 'Clinical manifestations'.)

●Gonads – The gonads are exquisitely sensitive to radiation exposure. Dose-dependent reduction in spermatogonia occurs as radiation increases. In adults, doses as low as 0.015 Gy can induce mild depression of spermatogenesis and those >6 Gy are likely to cause permanent sterility [28]. (See "Causes of male infertility", section on 'Drugs and radiation'.)

The effect of radiation on fertility in women varies with age, as described separately. (See "Fertility and reproductive hormone preservation: Overview of care prior to gonadotoxic therapy or surgery", section on 'Mechanism of injury'.)

●Eyes – The eyes are exposed when radioactive particles splash into or penetrate the unshielded cornea. Doses of radiation that otherwise would be of no significance can cause significant injury in this way. Exposure to doses as low as 0.2 Gy can induce cataracts, although the effects can be delayed for up to five years or longer. The importance of wearing eye protection when working with potentially hazardous radioactive material cannot be overstated [15]. (See "Cataract in children", section on 'Radiation'.)

Management of partial-body exposure injuries is discussed separately. (See "Management of radiation injury", section on 'Partial-body exposure'.)

EVALUATION — Evaluation should include information about the nature of the radiation exposure event (if available), a history of symptoms that may be related to radiation exposure, physical examination, and laboratory studies. The timing and severity of clinical findings and laboratory studies help to estimate the radiation "biodose."

Initial stabilization — Patients with acute radiation exposure may also have experienced acute injuries from trauma, blast, burn, or other aspects of the exposure event. These patients should undergo stabilization of life-threatening injuries prior to management of their radiation exposure. (See "Management of radiation injury".)

History and physical examination — The early findings related to acute radiation syndrome (ARS) are generally nonspecific but, depending primarily on dose, may include nausea, vomiting, diarrhea, abdominal cramping, bleeding, fatigue, fever, and mental status changes in the hours to days following radiation exposure (table 3). ARS generally follows a predictable time course, and it is important to document the time of onset of findings. The history should elicit symptoms related to the skin (eg, erythema, pruritus, burning sensation, blistering, ulceration), hematologic (eg, bleeding, infections, weakness), gastrointestinal (eg, nausea, vomiting, diarrhea, bleeding), and neurologic (eg, lethargy, ataxia, seizures, altered consciousness) systems. Details of the time course and clinical manifestations of ARS are discussed above. (See 'Acute radiation syndrome' above.)

Physical examination should include vital signs (fever, blood pressure, orthostatic changes) and evaluation of cutaneous (erythema, blistering, edema, desquamation), neurologic (level of consciousness, ataxia, motor/sensory deficits, reflexes, papilledema), gastrointestinal (abdominal tenderness, gastrointestinal bleeding), and hematologic systems (ecchymoses, petechiae).

The nature and extent of findings should be carefully documented. The patient accompanying documentation sheet is an example of a specific template for documentation of radiation injury [29]. Other methods are also acceptable (figure 1 and figure 2). The patient should be evaluated for contamination with a survey instrument (eg, Geiger-Muller counter), nasal and mouth swabs, and 24-hour collection of urine and stool specimens for radiation bioassay, as described separately. (See "Management of radiation injury".)

In some cases, the source and degree of radiation exposure will be known at the time of evaluation, based on occupation (eg, nuclear power plant worker or radiation technician), radiation monitoring data, or investigation of the incident. It may be difficult to distinguish symptoms associated with emotional trauma (eg, as a witness to a radiation exposure event) in unexposed patients from the clinical findings of radiation exposure, as discussed separately. (See "Management of radiation injury", section on 'Unexposed patients'.)

Laboratory studies — Initial laboratory studies should be performed for all patients with known exposure or potential exposure (eg, downwind from the site of a release of radioactive material, resulting in mass casualties).

Initial laboratory studies should include:

●Complete blood count (CBC) with differential; the time of CBC collection must be carefully noted, because of important time-related changes in the lymphocyte count (table 5). Serial CBCs should be obtained every 6 to 12 hours for at least three samples, and then once daily.

●Chemistries (eg, electrolytes, renal and liver function tests) should be monitored daily unless the patient's clinical condition requires more frequent monitoring.

●Baseline prothrombin time (PT) with international normalized ratio (INR), partial thromboplastin time (PTT), type and screen, and urinalysis.

●Twenty-four hours after any significant exposure, a blood sample should be drawn into a lithium heparin tube and sent to an appropriate referral lab for chromosomal aberration analysis for assessment of prognosis.

●For some patients with evidence of substantial radiation exposure (eg, early onset of mental status changes, vomiting, or skin burns), blood for human leukocyte antigen (HLA) typing should be obtained before the lymphocyte count falls, in the event that hematopoietic stem cell transplantation may be required.

Laboratory specimens from patients who may be contaminated with radioactive material should be placed in separate containers labeled with the name, date, time, and site of the sample collection.

DIAGNOSIS — Acute radiation injury should be suspected in an individual who has had potential exposure to radiation (eg, from medical exposure, industrial incident, or nuclear event) and findings that are consistent with radiation exposure (table 3). (See 'Recognition' above and 'Clinical manifestations' above.)

Radiation injury may also occur in an asymptomatic individual days to weeks after a known exposure, and it should be suspected in individuals without a known exposure event who exhibit otherwise unexplained findings suggestive of radiation injury (eg, unexplained erythroderma, gastrointestinal symptoms, cytopenias, and/or altered neurologic function). (See 'Recognition' above and 'Time course of ARS' above.)

The diagnosis of radiation injury is based on the presence of clinical findings that are consistent with the type, amount, and timing of radiation exposure (table 3), and laboratory studies (eg, serial lymphocyte counts and chromosomal aberration analysis) that support the diagnosis.

Radiologic survey with a detection device (eg, Geiger-Mueller counter) can identify asymptomatic patients with radiation contamination who are also exposed and at risk for radiation injury. (See "Management of radiation injury", section on 'Exposed and contaminated patients'.)  

ESTIMATION OF RADIATION EXPOSURE — Assessment of the extent of radiation injury is an ongoing process that often requires several days for accurate determination of the estimated dose of radiation exposure. Thus, patient management must occur before the estimated radiation dose is known. Estimation of radiation exposure is discussed separately. (See "Management of radiation injury", section on 'Estimation of radiation exposure'.)

DIFFERENTIAL DIAGNOSIS — The early clinical manifestations of radiation injury (ie, prodromal phase) are generally nonspecific, and may include anorexia, nausea, vomiting, and fatigue (table 3). In the absence of a known radiation exposure incident, the differential diagnosis is broad and may include gastroenteritis, heat stroke, viral infections, medications, autoimmune disorders, toxin exposures, and nutritional deficiencies.

For patients who exhibit clinical findings of acute radiation syndrome (ARS), the differential diagnosis is influenced by the nature of the findings but may include the following disorders:

●Aplastic anemia – Immune/idiopathic aplastic anemia (IAA)/paroxysmal nocturnal hemoglobinuria (PNH) or aplastic anemia caused by drugs, chemicals, or infections may be clinically indistinguishable from hematopoietic ARS. Both IAA/PNH and ARS may present with cytopenias; bleeding, infections, and fatigue; and aplastic/hypoplastic bone marrow. The history should distinguish radiation exposure from other causes of aplastic anemia, and flow cytometry can demonstrate a clonal population of CD59-positive PNH cells in peripheral blood or cytogenetic/molecular tests of bone marrow in most patients with IAA/PNH. Diagnosis of IAA/PNH is discussed separately. (See "Aplastic anemia: Pathogenesis, clinical manifestations, and diagnosis", section on 'Evaluation'.)

●Sepsis – Sepsis and systemic inflammatory response syndrome (SIRS) can cause fever, rash, bleeding, hypotension, cytopenias, confusion, and other findings that resemble ARS. Furthermore, infectious illnesses may result from the effects of radiation injury on bone marrow, the gastrointestinal tract, and central nervous system (CNS). Evaluation and diagnosis of sepsis/SIRS is discussed separately. (See "Sepsis syndromes in adults: Epidemiology, definitions, clinical presentation, diagnosis, and prognosis" and "Sepsis in children: Definitions, epidemiology, clinical manifestations, and diagnosis".)

●Drug reaction – Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare drug-induced hypersensitivity reaction that includes fever, skin eruption, hematologic abnormalities, lymphadenopathy, and dysfunction of liver, kidney, and lung that resembles manifest ARS. DRESS has a latency of two to eight weeks, a time frame that may be confused with radiation injury. DRESS is diagnosed by the presence of rash, fever, facial edema, lymphadenopathy, and peripheral blood eosinophilia and lymphocytosis in a patient who was exposed to a new drug up to six weeks earlier. The history of drug exposure and presence of lymphadenopathy, peripheral blood eosinophilia, and lymphocytosis should distinguish DRESS from ARS. (See "Drug reaction with eosinophilia and systemic symptoms (DRESS)".)

●Inflammatory bowel disease – Ulcerative colitis and other forms of inflammatory bowel disease (IBD) may present with abdominal pain, diarrhea, gastrointestinal bleeding, fever, fatigue, and anemia that resemble ARS. The diagnosis of colitis is based on chronic diarrhea, evidence of active inflammation on endoscopy, and characteristic changes on biopsy that distinguish IBD from ARS. Furthermore, patients with additional ARS findings of skin lesions, bone marrow failure, or CNS abnormalities are relatively easily distinguished from patients with IBD. The diagnosis of ulcerative colitis is discussed separately. (See "Clinical manifestations, diagnosis, and prognosis of ulcerative colitis in adults", section on 'Diagnosis'.)

●Thallium exposure – Exposure to thallium or other toxins may resemble clinical manifestations of ARS. Thallium toxicity can present with abdominal pain, nausea, vomiting, diarrhea, fatigue, headache, erythema, and skin rash; hair loss may progress to widespread alopecia over two to three weeks. Features peculiar to thallium exposure include the appearance of transverse white lines on the nails (Mees' lines), painful glossitis, scaling lesions on the palms and soles, acneiform eruptions of the face, paresthesias, dementia, and psychosis. The diagnosis of thallium toxicity is made by documenting an elevated blood thallium level. As an example, Alexander Litvinenko was treated with Prussian blue for thallium toxicity before the diagnosis of polonium-210 exposure was made [30].

PEDIATRIC CONSIDERATIONS — Children, especially infants and preschool children are more likely than adults to develop acute radiation injury because of their rapid growth and, thus, greater sensitivity to the biologic effects of radiation on rapidly dividing tissues [20]. In addition, fetal radiation exposure can have major consequences. The dose to the gravid uterus is approximately 65 to 70 percent of that to the body surface, which affords some protection to the fetus from external radiation exposure. However, when internal radiation contamination is present, the fetus may receive a high dose due to its proximity to the maternal bladder. The thyroid begins to take up iodine after 12 weeks, which adds to the potential for injury. The effects of ionizing radiation on the fetus include growth retardation; congenital malformations; embryonic, fetal, or neonatal death; and carcinogenesis. Specific dose thresholds for these effects are discussed separately. (See "Diagnostic imaging in pregnant and lactating patients", section on 'Fetal risks'.)

Several factors place children at greater risk for radiation exposure [20]:

●Children are more likely to encounter radioactive material from nuclear fallout near the ground where children live and breathe, and because they have greater minute ventilation, they are at a greater risk for exposure to radioactive gases.

●Because of their smaller body diameter and organ size, younger children are more likely to sustain higher levels of radiation exposure, regardless of the type of exposure (irradiation, internal contamination, or external contamination).

●Hand-to-mouth behavior and crawling places infants and young children at greater risk of exposure to contaminated soil.

●The typical diet of infants and young children places them at greater risk for ingestion of contaminated cow's milk due to contaminated cow pastures or cow feed or contaminated human breast milk due to maternal exposure.

Children are also at higher risk for long-term sequelae of radiation (eg, leukemia, thyroid cancer, cataracts, growth retardation, or infertility) even at doses that do not cause immediate injury, because they have more life expectancy and thus time to develop these complications.

MANAGEMENT — Management of radiation exposure is discussed separately. (See "Management of radiation injury".)

ADDITIONAL RESOURCES — Further guidance on the diagnosis and management of radiation exposure is available as follows:

●United States Health and Human Services: Radiation Emergency Medical Management – This website provides comprehensive guidance on diagnosis and treatment of a wide variety of radiation emergencies including nuclear reactor accidents, nuclear explosions, and radiological dispersal devices (eg, dirty bomb).

●Oak Ridge Institute for Science and Education (ORISE) – Hospital triage and medical aspects of radiation incidents, including detailed procedure demonstrations for decontamination are available.

●World Health Organization (WHO) – WHO maintains a website that provides useful information and documents for download in the event of an international radiation accident or emergency. The WHO report on national stockpiles for radiological and nuclear emergencies can be found here.

Regional poison control centers — In the United States, regional poison control centers are available to provide radiation exposure information and resources (eg, access to local radiation safety officers). In addition, some hospitals have medical toxicologists available for bedside consultation. To obtain emergency consultation with a medical toxicologist, in the United States, call 1-800-222-1222, or the nearest international regional poison center. Contact information for poison centers around the world is provided separately. (See "Society guideline links: Regional poison control centers".)

Society guideline links — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Radiation exposure in children".)

SUMMARY

●Radiation is the transfer of energy through space, which can occur in ionizing and nonionizing forms. Ionizing radiation is released by atoms that have an excess of energy, mass, or both (unstable atoms) in the form of X-rays, gamma rays, or particulate ionizing radiation (eg, alpha particles, beta particles, neutrons). The ability to penetrate human tissues and/or be shielded varies with the form of ionizing radiation, as described above. (See 'Radiation Physics' above.)

●Radiation can be expressed as the rate of disintegrations, which is measured in becquerels (Bq) or curies (Ci) (table 2). Radiation is also measured as dose rate (the amount of radiation delivered per unit time), which is expressed as grays (Gy) or radiation absorbed doses (rads), and as dose equivalents (the product of the absorbed dose rate and a weighting factor that reflects the relative biologic effectiveness on tissues), which is expressed as sieverts (Sv) or rems. (See 'Measures of radiation' above.)

●Biologic effects of radiation depend on the type of radiation; dose, schedule, and route of exposure; and the types of tissues that are exposed. Radiation injury may result from external irradiation or from internal or external contamination. Children, especially infants and preschool children, are more likely than adults to develop acute radiation injury because of their rapid growth and greater sensitivity to the biologic effects of radiation on rapidly dividing tissues (See 'Biologic effects of radiation' above and 'Types of radiation exposure' above and 'Pediatric considerations' above.)

●Radiation injury is most likely to be recognized because of an individual's proximity to a known exposure incident; this exposure may or may not be accompanied by a public announcement, indication of exposure from a monitoring device, clinical symptoms, or laboratory findings soon after the event. (See 'Recognition' above.)

●When a radiologic event is announced publicly or a patient with suspected radiation injury has arrived to the facility, hospital personnel should activate the facility's emergency medical response plan and obtain the necessary inhouse radiation safety personnel (ie, staff from Nuclear Medicine, Radiation Oncology, Radiology, and Radiation Safety) or obtain expert guidance from a regional poison control center (in the United States, call 1-800-222-1222 to be connected to the nearest poison control center; contact information for poison centers around the world is provided separately (see 'Additional resources' above)) or the Radiation Emergency Assistance Center and Training Site (REAC/TS) at Oak Ridge, Tennessee (after-hours phone number: 865-576-1005; general information phone number: 865-576-3131). (See 'Recognition' above and "Management of radiation injury", section on 'Facility planning and preparation'.)

●Acute radiation syndrome (ARS) occurs hours, days, or weeks after whole-body exposure (or large partial-body exposure) to sufficient penetrating radiation to cause clinically apparent injury. Initial clinical features are nonspecific, progress through three phases (ie, prodromal, latent, and manifest), and vary according to the degree and type of radiation exposure (table 3). (See 'Acute radiation syndrome' above and 'Time course of ARS' above.)

●There are four prominent subsyndromes of ARS:

•Cutaneous (table 4) (see 'Cutaneous' above)

•Hematopoietic (table 5) (see 'Hematopoietic' above)

•Gastrointestinal (table 6) (see 'Gastrointestinal' above)

•Neurologic (cerebrovascular) (table 7) (see 'Neurovascular syndrome' above)

●After stabilization of life-threatening conditions, evaluation for radiation injury should include a history of symptoms that may be related to radiation exposure, physical examination, selected laboratory studies, and information about the nature of the radiation exposure event. (See 'Evaluation' above.)

●Early findings related to ARS are generally nonspecific but, depending primarily on dose, may include nausea, vomiting, diarrhea, abdominal cramping, bleeding, fatigue, fever, and mental status changes in the hours to days following radiation exposure. Physical examination findings of burns, bruising, bleeding, or neurologic deficits within a few days of radiation exposure suggest a high dose. (See 'History and physical examination' above.)

●Laboratory studies should include type and screen, urinalysis, baseline prothrombin time (PT) with international normalized ratio (INR), partial thromboplastin time (PTT), and serial measures of complete blood count (CBC) with differential, electrolytes, and renal and liver function. (See 'Laboratory studies' above.)

●Diagnosis of ARS is based on the presence of clinical findings (table 3) that are consistent with the type, amount, and timing of radiation exposure, and laboratory studies (eg, serial lymphocyte counts) that support the diagnosis. Radiologic survey with a detection device (eg, Geiger-Mueller counter) can also identify asymptomatic patients with radiation contamination who are at risk for radiation injury. (See 'Diagnosis' above.)

●In the absence of a known radiation exposure incident, the differential diagnosis is broad and may include gastroenteritis, heat stroke, viral infections, medications, autoimmune disorders, and nutritional deficiencies. (See 'Differential diagnosis' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Erin E Endom, MD and Joseph Y Allen, MD, who contributed to earlier versions of this topic review.