Thallium Toxicity

Etiology

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 users, as well as skin absorption through protective gloves have been reported.[4][5][6][7]

Causes

• Occupational exposure
• Accidental ingestion
• Contaminated drug use
• Contaminated fish or other foods
• Exposure to hazardous waste sites
• Criminal poisoning

Epidemiology

Within the United States, 49 single exposures, with only one major outcome and no deaths were reported in 2019 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:

1. 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.
2. Riboflavin sequestration due to thallium and inhibition of flavin adenine dinucleotide disrupts the electron transport chain and decreases ATP production.
3. Thallium’s high ability for disulfide bonds disrupts cysteine residue cross-linking, causing a reduction in keratin formation.
4. Ribosomes are damaged by thallium’s effects on protein synthesis, especially the 60S ribosome.
5. 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:

1. Intravascular Distribution Phase: During the first 4 hours post-exposure, thallium is distributed to organs via the blood.
2. CNS Distribution Phase: During the next 4 to 48 hours, thallium reaches the central nervous system.
3. 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
• Seventh cranial 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 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 vision 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 
• Electrolyte
• 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 one hour of ingestion.[8][7][9](B3)

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.[10](B3)

Medications

• Prussian blue
• Activated charcoal

Differential Diagnosis

The presentation of thallium toxicity is similar to other toxicities and also mimics other diseases. Following differentials should be considered in patients with thallium toxicity.

• Carbon monoxide
• Arsenic 
• Isoniazid
• Mercury
• Organophosphates
• 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.[11] Neurologic damage may persist if detoxification therapy is delayed. Patients can have signs and symptoms of peripheral neuropathy up till six years after intoxication. Reports of persistent findings most commonly involve the feet and lower extremities.

Complications

Neurological damage may be persistent. The feet and lower extremities involvement have been most reported to be persistent. The following psychiatric symptoms also have been reported:

• Agitation
• Aggression
• Depression
• Personality changes