Continuing Education Activity
Thallium is a tasteless, odorless, and water-soluble element for which both accidental intoxication and criminal poisoning have been reported. The occupational exposure limit for thallium is 0.1 mg per cubic meter of skin for no longer than 8 hours a day. Levels of 15 mg per cubic meter and above are considered acutely dangerous. Thallium is readily absorbed both via inhalational and dermal routes.
Thallium toxicity poses a significant health risk, especially to individuals who may encounter this heavy metal through occupational exposure or environmental contamination. Workers in industries that use thallium or handle its compounds, such as electronics and glass manufacturing, are particularly vulnerable. Additionally, accidental ingestion or inhalation from contaminated food, water, or soil can lead to poisoning. At-risk groups also include individuals who live near hazardous waste sites and people exposed to illegal use of thallium in pesticides or rodenticides.
Evaluation of thallium toxicity involves a combination of clinical assessment and diagnostic tools. Symptoms of thallium poisoning can be nonspecific, ranging from gastrointestinal distress to neurological impairment, making early detection challenging. Diagnostic tests, such as serum thallium levels and 24-hour urine thallium excretion, are essential for confirming toxic exposure. Treatment primarily focuses on removing thallium from the body, typically through decontamination, Prussian blue administration, and, in severe cases, hemodialysis. Supportive care and symptomatic treatment are also critical to managing the effects of thallium poisoning effectively.
This activity for healthcare professionals is designed to enhance learners' proficiency in evaluating and managing thallium poisoning. Participants gain a deeper understanding of the condition's pathophysiology, symptomatology, and best practices for diagnosis and management. Greater competence equips clinicians to collaborate effectively within an interprofessional team caring for affected patients, improving outcomes.
Objectives:
Differentiate thallium poisoning from other toxidromes based on history and physical examination findings.
Create a clinically guided diagnostic plan for suspected thallium toxicity.
Implement a personalized, evidence-based management strategy for thallium poisoning.
Apply effective strategies to improve care coordination among interprofessional team members to facilitate positive outcomes for patients diagnosed with thallium toxicity.
Access free multiple choice questions on this topic.
Introduction
Thallium (Tl; atomic number 81) is a heavy metal know to cause a broad spectrum of adverse effects in humans.[1] Thallium sulfate was once used as an ant and rat poison.[2][3][4] The occupational limit for thallium skin exposure is 0.1 mg/m3 for 8 hours a day. [Occupational Safety and Health Administration, Thallium] Levels of 15 mg/m3 are considered immediately dangerous to one’s health.[1] Thallium is readily absorbed dermally and inhalationally.[5] As thallium is tasteless, odorless, and water-soluble, accidental and criminal intoxication has been reported.
Thallium salts were once used to treat dermatophytosis. The radioactive isotope thallous chloride Tl 201 was commonly used in stress tests before technetium Tc 99m became the standard for nuclear medicine studies; Tl 201 still used to evaluate coronary artery disease. Tl 201 is more than 4,000 times less potent than its toxic form. Scintigraphy with thallium assesses tissue blood supply by measuring thallium uptake. Normal coronary arteries dilate, altering blood distribution and potentially leading to reduced coronary circulation during exercise or the use of vasodilating drugs, a phenomenon known as coronary steal syndrome.[6]
Natural History
Thallium is a gray posttransition metal not found free in nature. Though similar to tin when isolated, thallium discolors when exposed to air. Patterns of thallium spread include dermal absorption, inhalation, and ingestion.[5]
Etiology
Thallium was banned from United States households in 1965, then commercially in 1975. Thallium intoxication often mimics other diseases. Thus, the condition is frequently overlooked in diagnoses. More recently, thallium has been used in the semiconductor and optical industries. Previously used as an insecticide and rodenticide, the element's lack of odor and taste properties has led to accidental poisonings and, in some cases, criminal use.
Although thallium is no longer used as a pesticide in the United States, it is still occasionally employed for this purpose in other countries. Contamination of Chinese herbal medications with thallium has also been reported. Intoxication can result from cumulative exposure through the skin, respiratory system, or gastrointestinal tract. Accidental insufflation or injection in individuals using cocaine or intravenous opioids, as well as skin absorption through protective gloves, has also been documented.[7][8][9] The causes of thallium toxicity include occupational exposure, accidental ingestion, contaminated drug use, eating contaminated foods like fish, exposure to hazardous waste sites, and criminal poisoning.[10]
Epidemiology
Within the United States, 49 single exposures, with only one major outcome and no deaths, were reported in 2019 through the National Poison Data Center.[11] Internationally, thallium toxicity is common in developing countries. However, little data is available.
Mortality and Morbidity
Mortality rates approximate 6% to 15% for acute thallium toxicity. Between 10 and 15 mg/kg is the lethal dose for humans. Death can still occur at lower doses.
Demographics
No data regarding age, sex, or race is available.
Pathophysiology
Thallium is structurally similar to potassium and is treated as such at the cellular level. Five major toxicologic effects are seen with thallium toxicity.
First, tissues with high potassium concentrations also accumulate large thallium concentrations, causing early stimulation, followed by inhibition of potassium-dependent processes. Inhibiting pyruvate kinase and succinate dehydrogenase disrupts the Krebs cycle and glucose metabolism. This interference reduces adenosine triphosphate (ATP) production and impairs the sodium-potassium ATPase channel, causing cellular swelling and vacuolization. Second, riboflavin sequestration due to thallium and inhibition of flavin adenine dinucleotide disrupts the electron transport chain and decreases ATP production.
Third, thallium’s high affinity for sulfur in disulfide bonds disrupts cysteine residue cross-linking, reducing keratin formation. Fourth, ribosomes are damaged by thallium’s effects on protein synthesis, especially the 60S ribosome. Fifth, thallium causes myelin degeneration in the central and peripheral divisions of the nervous system, though the mechanism remains unknown.
Toxicokinetics
The 3 toxicokinetic phases of thallium are as follows:
Intravascular distribution phase: During the first 4 hours postexposure, thallium is distributed to organs via the blood.
CNS distribution phase: During the next 4 to 48 hours, thallium reaches the central nervous system.
Elimination phase: This phase begins around 24 hours postexposure and is mainly achieved through renal excretion and feces. This slow phase may take up to 30 days.
History and Physical
Acute versus Chronic Exposure
Initial symptoms include gastrointestinal, neurological, and dermatological manifestations. Delayed alopecia is a hallmark of acute thallium poisoning. After prolonged exposure, acute poisoning symptoms persist, with neurological effects continuing even as blood thallium levels decrease.
Manifestations of Thallium Toxicity
Early gastrointestinal symptoms, presenting within 3 to 4 hours, include abdominal pain, nausea, vomiting, diarrhea or constipation, and, rarely, blood in vomitus or stool. Neurologic symptoms, typically presenting 2 to 5 days after exposure, include ascending and often severely painful peripheral neuropathies, distal motor weakness, ataxia, tremor, and cranial nerve palsies.
Dermatologic symptoms initially include nonspecific findings, such as scaling and acneiform or pustular eruptions. After 2 to 3 weeks, alopecia develops due to the disruption of cysteine disulfide bonds. Mees lines appear on the nails a month after poisoning. Other dermatological manifestations include hypohidrosis or anhidrosis and painful glossitis.
Ocular symptoms include diplopia, ptosis, 7th cranial nerve palsy, nystagmus, optic neuropathy, and lens opacities. Patients may experience tachycardia and hypertension. Other manifestations include headache, seizures, insomnia, and, in severe cases, coma. Death may occur in some cases.
Physical Examination
While the examination should focus on the affected areas, a comprehensive assessment, including neurologic, ophthalmologic, and gastrointestinal evaluations, is crucial. For the gastrointestinal assessment, a rectal examination and stool guaiac test should be performed alongside an abdominal examination. The neurological exam should assess all cranial nerves and check for nystagmus and ptosis. Lower extremity strength and decreased sensation to pinprick, touch, temperature, vibration, and proprioception should be evaluated. Severely painful peripheral neuropathy is a classic presentation of thallium poisoning. For the ophthalmologic evaluation, slit lamp and funduscopic examinations should be conducted, and visual acuity and color vision should be assessed.
Evaluation
Laboratory Tests
Elevated thallium levels in hair, nails, blood, urine, feces, and saliva can aid in establishing a diagnosis. The standard method for measuring thallium concentration is a 24-hour urine test, analyzed by inductively coupled plasma mass spectroscopy (ICP-MS). Although hair, saliva, and feces testing have been used, urine is preferred for clinical use. Atomic absorption spectroscopy, while less accurate than ICP-MS, may still be employed. A urine spot test provides quicker results but has a high false-positive rate, and blood thallium levels may be falsely negative. Additional tests to consider include a complete blood count with differential, electrolyte levels, glucose, blood urea nitrogen, liver function tests, and calcium.
Radiography
Thallium is radiopaque. Radiographs may reveal the presence of this heavy metal in the body after ingestion.
Ancillary Tests
Arrhythmias are rare complications and should be evaluated through electrocardiography. An electroencephalogram is recommended for any seizure-like activity, and a nerve conduction study should be performed for patients experiencing neurological symptoms.
Treatment / Management
Much like many other toxic exposures, care starts with stabilization, airway, breathing, and circulation, as well as removal of contaminated clothing. Activated charcoal, Prussian blue, or both can be used for internal decontamination after ingestion and should be administered as early as possible. [12][10][13]
If the patient is dermally exposed, their skin should be washed with soap and water. For eye exposure, the eyes should be irrigated with room-temperature water or saline. Activated charcoal and Prussian blue may be used for gastrointestinal ingestion.
Prussian blue is the treatment of choice for thallium poisoning and results in reduced enterohepatic recirculation of thallium, enhancing its elimination. The typical dose is 250 mg/kg per day in 2 or 4 divided doses. A definitive end point of therapy has not been established. Prussian blue can be mixed in 15% mannitol or administered with polyethylene glycol for patients with constipation.
Compared to activated charcoal, Prussian blue is more effective and has been approved by the United States Food and Drug Administration.[14] Multidose activated charcoal should be used in cases where Prussian blue is not available.
Hemodialysis can also enhance the elimination of thallium. The use of this method is typically isolated to cases where gastrointestinal decontamination with either Prussian blue or activated charcoal is not feasible. Consultation with a medical toxicologist and nephrologist should be obtained if extracorporeal elimination procedures, such as hemodialysis, are considered.
Differential Diagnosis
The presentation of thallium toxicity is similar to other toxicities and also mimics other diseases. The following alternative diagnoses should be considered in patients with thallium toxicity:
Thallium poisoning can be challenging to diagnose, given its similarity to other toxicities and diseases. A thorough clinical evaluation and diagnostic workup, considering the above alternative conditions, help ensure accurate diagnosis and appropriate treatment.
Prognosis
The prognosis for patients with thallium toxicity depends on the dose ingested and the presence of neurological symptoms. Patients with minimal symptoms can fully recover with treatment, but individuals with severe toxicity may have persistent alopecia, neuropathy, and psychiatric effects.
Early diagnosis and treatment portend a better prognosis.[15] Neurologic damage may persist if gastrointestinal decontamination therapy is delayed. Patients can have signs and symptoms of peripheral neuropathy for many years after poisoning. Reports of persistent findings most commonly involve painful neuropathy of the lower extremities.
Complications
Neurological damage may be persistent. Involvement of the lower extremities has been reported to be the most likely to remain. Alopecia is common. Psychiatric symptoms that have also been reported include agitation, aggression, depression, and personality changes.
Consultations
Consultation with a medical toxicologist or a Poison Center should be obtained for any patient with suspected thallium poisoning.
Deterrence and Patient Education
Patients unintentionally exposed to thallium should wash their skin with tap water and remove contaminated clothing as soon as possible. Intentional ingestions mandate a psychiatric evaluation once stable. Mouth hygiene should be closely monitored. Shaving the patient's head may reduce the stress induced by hair loss and improve the patient's morale. All patients should have close follow-up care.
Enhancing Healthcare Team Outcomes
Thallium toxicity should be managed by an interprofessional team that includes an emergency medicine physician, medical toxicologist, internist, neurologist, nurse practitioner, and intensivist. The triage nurse should follow protocols for patients suspected of poisoning, including possible decontamination. The emergency provider should communicate with the interprofessional team.
The initial management of thallium toxicity requires assessing the airway, breathing, circulation, and any need for decontamination. The nurses play an active role in resuscitation by ensuring intravenous access, providing oxygenation, documenting the event, and placing the patient on monitoring devices. Activated charcoal may be used for patients presenting within an hour of ingestion. Dermal exposure necessitates washing the skin with soap and water. For eye exposure, copious irrigation of the eyes with room-temperature water or saline is necessary.
Activated charcoal and Prussian blue may be used for gastrointestinal ingestions. Prussian blue has been shown to be more successful and is approved by the United States Food and Drug Administration. After resuscitation, the circumstances of how and why the patient ingested thallium should be assessed. If the ingestion was intentional, a mental health nurse should evaluate the patient before discharge. Finally, evaluation by a neurologist is recommended to determine the extent of neurological deficits. Open communication with the members of the interprofessional team can help limit the morbidity of thallium toxicity.
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Disclosure: Tyler Kemnic declares no relevant financial relationships with ineligible companies.
Disclosure: Meghan Coleman declares no relevant financial relationships with ineligible companies.
