Arsenic Poisoning (Arsenic Toxicity)

Arsenic contamination areas[1]

Arsenic poisoning can present in both acute and chronic forms. Acute arsenic poisoning is marked by shock like symptoms and chronic toxicity is characterized by systemic effects that include neuropathy, encephalopathy, dermatitis, renal and liver dysfunction. The metal has also been associated with various cancers in humans.

Presentation

When a patient presents with arsenic overdose it is important to obtain a proper history to determine how the arsenic got in the body. In some cases, the cause may be accidental ingestion but in others it may be related to an occupation or an intentional attempt by others to poison the individual. In all cases of poisoning, it must be determined if this was an suicidal attempt. Paresthesias and peripheral neuropathy are common symptoms of a work-related arsenic poisoning. When the individual presents with symptoms of arsine gas exposure, this is usually also related to an occupational accident. These patients frequently develop rapid symptoms and are often brought immediately to the ED.

It is also important to determine if the individual is consuming health supplements [6], herbs or any other exotic substances like adulterated alcoholic beverages. Over the years, many cases of arsenic overdose have resulted in people who have resorted to taking arsenic supplements for treatment for a wide range of medical disorders [7].

Individuals with arsenic toxicity may present with complaints of:

In acute and chronic cases, the following features may be seen on physical exam:

Workup

When arsenic toxicity is suspect the following studies are needed:

  • Complete blood count. The hemolysis may present with anemia and thrombocytopenia. Eosinophilia is sometimes seen during acute arsenic poisoning [8].
  • Blood must be typed and cross matched because there may be a need for blood transfusion due to hemolysis.
  • Blood smear may reveal basophilic stippling, schistocytes and fragmented red blood cells.
  • Electrolyte levels are often altered because arsenic induced severe vomiting and diarrhea
  • Levels of arsenic can be measured but it is important to differentiate between organic and inorganic arsenic. Organic arsenic is often found in humans but does not require any treatment.
  • Measure levels of arsenic in plasma. When levels of arsenic are greater than 50 microgram/L in blood, adverse effects usually appear.
  • The urine microscopy studies may reveal presence of red cell casts, proteinuria and hemoglobinuria.
  • If chronic arsenic poisoning is suspected, levels of arsenic in the hair and fingernails can be measured. However, it is important to check the ambient levels of arsenic in that particular environment to ensure that the metal has not leached into the hair from outside.
  • Because arsenic is a potential teratogen, all females of child bearing age must have a urine pregnancy test done.
  • When suicide or intentional harm is suspected, urinary levels of other drugs and coingestants like amphetamine, cocaine, oxycodone, acetaminophen and benzodiazepines should be done.

Other tests

  • An abdominal X-ray may reveal presence of white deposits in the stomach or small bowel. 
  • Patients who present with paresthesias and neuropathy should undergo nerve conduction studies when stable.
  • An ECG is indicated because arsenic is known to induce arrhythmias.

Treatment

If the patient is acutely toxic and found outside the hospital, resuscitation will be needed before bringing him/her to the ED. The airway must be protected during transport. In the ED, maintenance of hemodynamic stability is the goal. These patients often require large volumes of crystalloid because of the repeated vomiting and diarrhea. In some cases, patients may even require blood transfusions. Electrolytes also need to be replaced.

The use of agents to decontaminate the gastrointestinal tract is fraught with controversy. If the patient presents soon after ingestion of arsenic or a plain X-ray reveals presence of arsenic in the stomach, orogastric lavage is recommended. The use of activated charcoal is not beneficial as it does not bind to arsenic. Some poison experts also recommend the use of polyethylene glycol whole body irrigation to prevent arsenic absorption. Use of endoscopy to empty and lavage the stomach is not recommended as older reports indicate that it has very low success rates. No matter what decontamination process is undertaken, definitive treatment that includes hemodialysis and chelation should not be delayed in symptomatic patients. To determine the type of chelation agent, one should consult with the local poison control center.

For dialysis a nephrologist should be consulted. However, if the patient has no renal dysfunction, dialysis will not improve outcome. Once the patient has been stabilized, a complete neurologic exam is warranted as residual neuropathy is not uncommon. If the patient took arsenic to commit suicide, a psychiatry consult should be made before the patient is discharged home.

The treatment of arsenic toxicity is hydration and supportive care. Chelation treatment is used in symptomatic patients. Unfortunately despite 30 years of using chelators, definitive evidence for chelators in improving clinical symptoms of patients with arsenic toxicity is lacking [9]. Chelating agents used to treat arsenic toxicity include Dimercaprol, Succimer and Dimerval. Unfortunately, these agents are not always available in all emergency rooms. Once the acute toxicity has been treated, many individuals will probably require long term rehabilitation because of the severe peripheral neuropathy.

Prognosis

In western countries, a few deaths are reported each year. Elsewhere medical record keeping is not rigid and hence the exact numbers of deaths from arsenic are not known. Chronic exposure to arsenic has been associated with heart disease, neuropathy, dermatitis, liver and renal dysfunction, encephalopathy and visual problems. There is also concern that prolonged exposure of arsenic can lead to development of lung, liver, kidney and skin cancers [5].

Etiology

Arsenic was once used as an herbicide and rodenticide which was often the cause of overdose in children. In addition, arsenic was also used to treat pressurized wood and humans acquired it though transdermal absorption. The use of arsenic in pressured wood is now banned.

Arsenic exposure may occur in adults who work in the mining industry or in metal, glass or semiconductor production. Over the years, small amounts of arsenic have been found in glues, wines, and other common products. Organic arsenic is present in many foods and is harmless, but in some parts of the world, inorganic arsenic has also become part of the food chain because of improper disposal. Arsenic has been detected in vegetables, dairy products, meat and cereals and there are reports of arsenic being found in rice in several countries in Southeast Asia. 

Epidemiology

Arsenic poisoning occurs chiefly in people who come in contact with pesticides and those who work in the mining industry or in metal, glass or semiconductor production. In most western countries, the levels of arsenic in the environment are rigidly controlled. In Asia and especially Bangladesh, arsenic is very prevalent in the environment and in the drinking water. Millions of people who live in Bangladesh have extremely high levels of arsenic in the blood. So far efforts to reduce arsenic levels in Bangladesh have not been a success. This partly because the major industries continue to dump industrial waste in the surrounding waters. The problem is compounded by the fact that this population also has marked deficiency of certain vitamins and antioxidants in their diet, which is also a factor in enhancing toxicity of arsenic. The WHO recommends that there should not be more than 10 parts per billion of arsenic in drinking water, but levels in Bangladesh at least a hundred fold higher. Recent studies reveal that drinking water containing as little as 17 ppb can lead to arsenicosis over a period of time [2] [3].

Men are more prone to arsenic toxicity primarily because they work in the mining industry. In addition in developing countries women and children are also more likely to work in the farming industry, where they may be exposed to pesticides [4]. In children the majority of cases of arsenic toxicity are due to arsenic containing pesticides where in adults the exposure to arsenic is chiefly from the mining industry.

Sex distribution
Age distribution

Pathophysiology

Arsenic is a systemic poison and it may affect basically all organs. It is the inorganic arsenic that is toxic to humans. Organic arsenic is commonly found in the environment and even in certain foods, but it is not a potent toxin compared to the inorganic form. The inorganic arsenic occurs as a trivalent or pentavalent compound and is highly reactive. Both forms have the ability to bind to thiol groups in enzymes leading to uncoupling of oxidative phosphorylation, with a resulting decrease in generation of adenosine triphosphate (ATP).

Inorganic arsenic also affects other metabolic pathways and interferes with glucose transport across cells, inhibits fatty acid oxidation and decreases production of glutathione. Arsenic is also a potent generator of oxidative free radicals including superoxide anion. The pentavalent inorganic arsenic can also interfere with generation of the action potential and lead to arrhythmias. This adverse effect is potentiated by electrolyte depletion that also occurs in patients with arsenic overdose.

Besides the metal, people can also get exposed to arsine gas when working in the mining industry. This toxic gas is inhaled and can rapidly produce respiratory distress, hemolysis, central nervous system (CNS) toxicity and multiorgan failure. The adverse effects are often irreversible and urgent medical attention is required to save the patient.

Prevention

Arsenic toxicity can be prevented by avoiding contact with pesticides. When working in the mining industry, one needs to wear proper garments, mask and gloves. Periodic assessment of arsenic levels may help determine if one is developing high levels. The government is responsible for regulating the industries and ensure that they do not dispose industrial waste in the waterways.

Summary

Arsenic poisoning is not common in most western nations but it is a cause for concern in some Asian and African countries. Arsenic toxicity may occur from exposure to pesticides or from industrial exposure. Arsenic toxicity is also being increasingly reported in people who consume adulterated alcoholic beverages, use certain herbal preparations or are poisoned. More important is that there is now interest in developing arsenic formulas for the treatment of various hematological malignancies, but there is concern that it may also contribute to arsenic toxicity. Arsenic is a systemic poison and has the potential to affect every organ in the body. There is growing evidence that arsenic may also cause cancer [1].

Patient Information

Arsenic is a metal that is sometimes found in pesticides and some herbal products. People who work in the mining industry can also be exposed to arsenic and the gas that is generated, called arsine gas. Even short term exposure to arsenic can lead to acute toxicity that can present with bloody in the stools, vomiting and abdominal pain. Prolonged exposure to arsenic can lead to numbness, tingling and painful sensations in the legs and arms.There are also data to indicate that arsenic exposure can lead to cancer. Anyone who has been exposed to arsenic or presents with vague symptoms as described above, should seek medical assistance. Arsenic toxicity can be easily detected by measuring levels of the metal in urine or blood. Treatment of arsenic is avoidance of exposure and supportive care.

Self-assessment

References

  1. Watanabe T, Hirano S. Metabolism of arsenic and its toxicological relevance. Arch Toxicol. 2013 Jun;87(6):969-79.
  2. Shankar S, Shanker U, Shikha. Arsenic contamination of groundwater: a review of sources, prevalence, health risks, and strategies for mitigation. ScientificWorldJournal. 2014;2014:304524
  3. Majumdar KK, Guha Mazumder DN. Effect of drinking arsenic-contaminated water in children. Indian J Public Health. 2012 Jul-Sep;56(3):223-6.
  4. El-Bahnasawy MM, Mohammad Ael-H, Morsy TA. Arsenic pesticides and environmental pollution: exposure, poisoning, hazards and recommendations. J Egypt Soc Parasitol. 2013 Aug;43(2):493-508.
  5. Huang L, Wu H, van der Kuijp TJ. The health effects of exposure to arsenic-contaminated drinking water: a review by global geographical distribution. Int J Environ Health Res. 2014 Nov 3:1-21.
  6. Posadzki P, Watson L, Ernst E. Contamination and adulteration of herbal medicinal products (HMPs): an overview of systematic reviews. Eur J Clin Pharmacol. 2013 Mar;69(3):295-307.
  7. Rehman K, Naranmandura H. Double-edged effects of arsenic compounds: anticancer and carcinogenic effects. Curr Drug Metab. 2013 Dec;14(10):1029-41.
  8. Kosnett MJ The role of chelation in the treatment of arsenic and mercury poisoning. J Med Toxicol. 2013 Dec;9(4):347-54
  9. Dangleben NL, Skibola CF, Smith MT. Arsenic immunotoxicity: a review. Environ Health. 2013 Sep 2;12(1):73.



Media References

  1. Arsenic contamination areas, CC BY-SA 3.0

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