Thallium Toxicity
- Article Author:
- Tyler Kemnic
- Article Editor:
- Meghan Coleman
- Updated:
- 7/10/2020 1:31:59 AM
- For CME on this topic:
- Thallium Toxicity CME
- PubMed Link:
- Thallium Toxicity
Introduction
Thallium, a chemical element with the symbol TI, has an atomic number 81 of the periodic table. Thallium sulfate was once used as an ant and rat poison.[1][2][3]
The occupational limit for thallium exposure is 0.1 mg/m^3 to the skin per 8 hours a day. Levels of 15mg/m^3 are considered immediately dangerous to one’s health. Thallium (1) is readily absorbed through the skin as well as during inhalation. Due to thallium being tasteless, odorless, and water-soluble, accidental and criminal intoxication have been reported.
Similar thallium salts were once used to treat dermatophytosis. Before the use of technetium-99m for nuclear medicine studies, thallium-201, a radioactive isotope, was the mainstay and is still used for stress tests evaluating coronary artery disease. (This type of thallium is more than 4000 times less potent.) Scintigraphy using thallium evaluates blood supply to tissue thallium uptake. Exercise or drugs used to vasodilate normal coronary arteries causes alteration of circulating blood, leading to a reduction of coronary blood circulation (coronary steal syndrome).
Natural History
Thallium is a gray post-transition metal that is not found in free nature. Though similar to tin when isolated, Thallium discolors when exposed to air.
Patterns of Spread
- Absorbed through the skin
- Respiratory inhalation
- Absorption through the gastrointestinal tract
Etiology
Causes
- Occupational exposure
- Accidental ingestion
- Contaminated drug use
- Contaminated fish or other foods
- Exposure to hazardous waste sites
- Criminal poisoning
In 1965 thallium was banned from United States households and, subsequently, banned commercially in 1975. Due to intoxication often mimicking other diseases, ill patients may go unnoticed. More current uses of thallium are in the semiconductor and optical industries. Thallium is used in rat poison and ant killer, and because it is both odorless and tasteless, it has become an accidental intoxication as well as a criminal poison in some cases. To this day, thallium is seen in rodenticide and insecticide in other countries. In Africa, thallium has been used as a pesticide, which has led to food contamination. Chinese herbal medications also have been contaminated. Intoxication occurs by cumulative intake through the skin, respiratory, and gastrointestinal tracts. Accidental snorting by cocaine abusers, accidental injection by heroin uses, as well as skin absorption through protective gloves have been reported.[4][5][6][7]
Epidemiology
Frequency
Within the United States, 29 single exposures, with only one major outcome and no deaths were reported in 2016 by the American Association of Poison Control Center. Internationally thallium toxicity is common in developing countries; however, little data is available.
Mortality/Morbidly
Six percent to 15% has been reported for acute thallium toxicity.
Ten to 15 mg/kg is a lethal dose for humans. Death can still occur at lower dosages.
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. The following five major toxicologic effects are seen with thallium toxicity:
- Tissues with high potassium concentrations also accumulate large concentrations of thallium. This causes early stimulation, followed by inhibition of potassium-dependent processes. Inhibiting pyruvate kinase and succinate dehydrogenase leads to disruption of the Kreb’s cycle and glucose metabolism, with a result of decreased ATP production, swelling, and vacuolization due to impairment of the sodium-potassium ATPase.
- Riboflavin sequestration due to thallium and inhibition of flavin adenine dinucleotide disrupts the electron transport chain and decreases ATP production.
- Thallium’s high ability for disulfide bonds disrupts cysteine residue cross-linking, causing a reduction in keratin formation.
- Ribosomes are damaged by thallium’s effects on protein synthesis, especially the 60S ribosome.
- Lastly, thallium causes degeneration of myelin in the central and peripheral nervous systems, though the mechanism remains unknown.
Toxicokinetics
The three toxicokinetic phases of thallium are as follows:
- Intravascular distribution phase: During the first 4 hours post-exposure, 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 post-exposure and is mainly achieved through renal excretion and feces. This is a slow phase and may take up to 30 days.
History and Physical
Acute Exposure
Symptoms include gastrointestinal, neurological, and dermatological.
Chronic Exposure
Results in continuation of the above; however, neurological symptoms persist even as blood thallium levels decrease.
Gastrointestinal symptoms (presenting early within 3-4 hours)
- Abdominal pain
- Nausea/Vomiting
- Diarrhea or constipation
- Rarely vomitus or stool containing blood
Neurologic symptoms (presenting later around 2-5 days post-exposure)
- Ascending peripheral neuropathies
- Distal motor weakness
- Ataxia
- Tremor
- Cranial nerve palsies
- Headache
- Seizures
- Insomnia
- Coma
- Death may occur
Ocular symptoms
- Diplopia
- Ptosis
- CN VII nerve palsy
- Nystagmus
- Optic neuropathy
- Lens opacities
Dermatologic symptoms
At first nonspecific findings such as scaling and acneiform/pustular eruptions may occur. After 2 to 3 weeks, alopecia begins due to the cysteine disulfide bond disruption. One month after poisoning, Mees lines appear on the nails.
- Hypohidrosis
- Anhidrosis
- Painful glossitis
Other Symptoms
Patients may experience tachycardia and/or hypertension.
Physical
Though the exam should focus on the affected areas, a neurologic, ophthalmologic, and gastrointestinal examination is crucial.
- Abdominal/GI: A rectal examination and stool guaiac test should be performed with an abdominal examination.
- Neurological: All cranial nerves, nystagmus, and ptosis may be present. Lower extremity strength, as well as decreased sensation to pinprick, touch temperature, vibration, and proprioception, may be present.
- Ophthalmologic: Slit lamp and funduscopic exams while evaluating visual acuity and color are needed.
Evaluation
Laboratory
Only elevated thallium levels in hair, nails, blood, urine, feces, and saliva can make a definitive clinical diagnosis. A 24-hour urine thallium concentration, assayed by atomic absorption photospectrometry, is the standard method. Although a urine spot test is faster, it has a high false-positive rate. Blood thallium levels may be falsely negative. The following are other tests to order:
- Complete blood count with differential
- Electrolytes
- Glucose
- Blood urea nitrogen
- Liver function test
- Calcium
Radiographic
Thallium is radiopaque. Thallium may be reviled after ingestion.
Other Tests
Electrocardiograms should be ordered to evaluate for arrhythmias and tachycardia. An electroencephalogram should be ordered for any seizure-like activity as well as a nerve conduction study for patients experiencing neurological symptoms.
Treatment / Management
Initial Care
Much like many exposures, care starts with stabilization, airway, breathing, and circulation, as well as removing contaminated clothing. Activated charcoal can be used for patients presenting within 1 hour of ingestion.[8][7][9]
Emergency Department
If the patient had dermal exposure, their skin is to be washed with soap and water. For eye exposure, irrigate the eyes with room temperature water. Activated charcoal and Prussian blue may be used for gastrointestinal ingestion. Prussian blue has been shown to be more successful and is approved by the United States Food and Drug Administration.
Medications
- Prussian blue
- Activated charcoal
Differential Diagnosis
Differential of Other Toxicities
- Carbon monoxide
- Arsenic
- Isoniazid
- Mercury
- Organophosphates
Differential Diagnosis
- Thiamine deficiency
- Diabetic polyneuritis
- Botulism
- Vasculitis
- Poliomyelitis
Prognosis
The sooner treatment is initiated the better the prognosis although chronic exposure may have a long recovery.
Complications
Neurological damage may be persistent. The feet and lower extremities have been most reported to be persistent. The following psychiatric symptoms also have been reported:
- Agitation
- Aggression
- Depression
Postoperative and Rehabilitation Care
Patients who intentionally ingest thallium should have a psychiatric evaluation. All patients should have close follow up care.
Consultations
- Regional posion control center
- Medical toxicologist
Enhancing Healthcare Team Outcomes
The management of thallium toxicity is by an interprofessional team that includes an emergency department physician, poison control, internist, neurologist, nurse practitioners, and an intensivist. The triage nurse should follow protocols for patients suspected of poisoning and have them admitted right away. The next step is to notify the emergency department physician, who will communicate with the interprofessional team.
The initial management of a patient with thallium toxicity follows the trauma ABCDE protocol. The nurses play an active role in resuscitation by ensuring IV access, providing oxygenation, documenting the event, and placing the patient on monitoring devices. Activated charcoal can be used for patients presenting within 1 hour of ingestion. If the patient had dermal exposure, their skin is to be washed with soap and water. For eye exposure, irrigation of the eyes with room temperature water is necessary.
Activated charcoal and Prussian blue may be used for gastrointestinal ingestion. Prussian blue has been shown to be more successful and is approved by the United States Food and Drug Administration. After resuscitation, it should be determined how and why the patient ingested thallium; if it was intentional, then the patient must be seen by a mental health nurse prior to discharge. Finally, the patient must be seen by the neurologist to determine the extent of neurological deficits.
Only through open communication with the members of the interprofessional team can the morbidity of thallium toxicity be lowered.
Outcomes
The prognosis for patients with thallium toxicity depends on the dose ingested and the presence of neurological symptoms. Those with minimal symptoms can fully recover with treatment, but patients with severe toxicity may continue to have neuropsychiatric deficits for a long time. (Level V)