Clinical Pearls & Morning Reports
Arsenic is a natural component of the earth’s crust and therefore is widely distributed throughout the environment, mostly in trivalent and pentavalent forms. Worldwide, the greatest threat to public health from arsenic is through contaminated groundwater. Read the latest Clinical Problem-Solving here.
Q: Is it the organic forms or inorganic forms of arsenic that are toxic?
A: Trivalent and pentavalent forms of arsenic, as well as their methylated metabolites monomethylarsonic acid and dimethylarsenic acid, are toxic, and the trivalent form is most potent. Organic forms, such as the arsenobetaine found in fish and other seafood, are nontoxic.
Q: What types of cancer are associated with long-term exposure to arsenic?
A: Long-term exposure to arsenic has been associated with an increased risk of cancer, particularly skin, bladder, and lung cancer. The World Health Organization suggests a level in drinking water of less than 10 μg of arsenic per liter to reduce the risks associated with long-term arsenic exposure.
A: After acute high-dose exposure to inorganic arsenic, symptoms can develop within minutes to hours and progress to severe systemic manifestations and death. Symptoms typically begin in the gastrointestinal tract with vomiting, abdominal pain, and severe watery diarrhea that results in dehydration and hypotension. Gastrointestinal hemorrhage can occur. Patients may hypersalivate and have a garlicky odor on their breath. Acute encephalopathy may develop over several days, with delirium, seizures, and progression to coma. Renal impairment, liver dysfunction, adult respiratory distress syndrome, and cardiac dysfunction (including prolongation of the QTc interval and arrhythmias) occur in severe cases. Symptoms in less severely poisoned patients include persistent gastroenteritis and mild hypotension along with a metallic taste and irritated mucous membranes that can mimic pharyngitis. In patients who survive the initial illness, hepatitis and pancytopenia may develop within the first week. Bone marrow suppression reaches a maximum at 2 to 3 weeks. A painful peripheral neuropathy typically develops 1 to 3 weeks after exposure and may not respond to chelation therapy. The effects of chronic toxicity are insidious and thus more difficult to diagnose. Skin manifestations and peripheral neuropathy are more prominent than gastrointestinal symptoms. There is an association between arsenic poisoning and reactivation of varicella–zoster virus.
A: Inorganic arsenic is rapidly cleared from the blood; therefore, 24-hour urinary arsenic level is the best measure of exposure. Urine tests measure total arsenic level, including both toxic inorganic arsenic compounds and nontoxic organic arsenic compounds found in fish, other seafood, and other foods. Ideally, a urine specimen should be obtained after a patient has abstained from eating fish for at least 3 days, and specimens that test positive for arsenic should be assessed further to distinguish toxic from nontoxic species. An important consideration in case management is identification and elimination of the source, when possible. In addition to supportive care and resuscitation, critically ill patients with known or suspected arsenic poisoning should undergo chelation therapy while awaiting results from urine tests. In patients who are not critically ill, chelation therapy is indicated if urine levels of inorganic arsenic are elevated. Dimercaprol (previously known as British antilewisite, or BAL) and its water soluble metabolites succimer and unithiol are commonly used, although unithiol does not have approval from the Food and Drug Administration for this indication. Intramuscular dimercaprol has a narrow therapeutic index, and oral chelation with succimer is preferable. Although chelation therapy increases urinary clearance of arsenic, it may not prevent progression of peripheral neuropathy.