- Author: Steven Marcus, MD; Chief Editor: Asim Tarabar, MD more...
Arsenic poisoning occurs through industrial exposure (see the image below), from contaminated wine or moonshine, or due to malicious intent. It may also occur through heavy metal contamination of herbal preparations and so-called nutritional supplements. A resurgence of interest in arsenic as a medicinal agent for the treatment of acute promyelocytic leukemias, multiple myeloma, myelodysplastic syndromes, and assorted resistant solid tumors may potentially contribute to arsenic toxicity.
See Clues on the Skin: Acute Poisonings, a Critical Images slideshow, to help diagnose patients based on their dermatologic presentations.
Signs and symptoms
Arsenic exposure is usually associated with suicide, malicious intent, homicide, or occupational exposure. A detailed history to determine the exposure includes the following:
Careful work history on individuals with a painful peripheral neuropathy
Careful history regarding dietary and nutritional habits (eg, use of nutritional supplements and ayurvedic medicines, alcohol abuse) and hobbies
Clinical effects of arsenic toxicity depend on the chronicity (eg, acute, chronic) and type of poisoning (eg, arsenic, trivalent arsenic, arsine gas). Frequently, patients exposed to arsenic have a garlic smell to their breath and tissue fluids.
Acute severe arsenic poisoning manifests with the following signs and symptoms:
Tachycardia, hypotension, and even shock
Altered mental status, delirium, coma, seizures (acute encephalopathy)
Trivalent arsenic poisoning manifests with the following signs and symptoms:
Acute exposure: Cholera-like gastrointestinal (GI) symptoms of vomiting (often bloody) and severe diarrhea (may be rice-watery, often bloody); these patients will experience acute distress, dehydration (often), and hypovolemic shock
Chronic toxicity: Insidious; may manifest as a classical dermatitis (hyperkeratosis with a classical "dew drops on a dusty road" appearance) or peripheral neuropathy (usually a painful, symmetrical paresthesia with stocking-glove distribution); commonly, hepatic and renal damage
Fingernails: Whitish lines (Mees lines) that look like those from traumatic injuries
Arsine gas exposure manifests with an acute hemolytic anemia and striking chills.
See Clinical Presentation for more detail.
Complete blood count: Microcytic hypochromic anemia common; with arsine exposure, acute hemolytic anemia is the rule
Serum electrolyte levels, including calcium and magnesium
Type and screen or cross-match blood: For transfusion in patients exposed to arsine gas
Plasma arsenic concentrations: Helpful, but results usually not available until treatment decision has been made
Urinalysis: Urine spot test for arsenic and 24-hour urine collection for total arsenic excretion; patient must not have consumed seafood for at least 3 days prior to urine collection; laboratory must “speciate” the arsenic into organic and inorganic moieties, because the inorganic form is responsible for symptoms and signs of arsenic toxicity
Urine pregnancy test
Serum acetaminophen levels
Abdominal x-ray: May reveal radio-opaque densities; may resemble an upper GI series
Nerve conduction studies: May confirm peripheral neuropathy
Electrocardiography: May reveal cardiac arrhythmias/failure from arsenic toxicity
See Workup for more detail.
Treatment of acute arsenic toxicity is supportive. Chelation therapy is imperative in all symptomatic patients; however, the use of chelators in patients exposed to arsine gas is controversial.
Support airway, breathing, and circulation
Hemodynamic stabilization: May include infusing large amounts of crystalloid solutions and the use of blood products
Acute arsenic ingestions: Orogastric lavage if the patient presents rapidly or plain radiography indicates that arsenic is present in the stomach; whole bowel irrigation with polyethylene glycol may be effective to prevent GI tract absorption of arsenic
Definitive chelation therapy; may be controversial for argine gas toxicity
The following chelating agents are used in the management of arsenic toxicity:
Arsenic, element 33, has a long and nefarious history; its very name has become synonymous with poison. In the 15th and 16th centuries, the Italian family of Borgias used arsenic as their favorite poison for political assassinations. Some even have suggested that Napoleon was poisoned by arsenic-tainted wine served to him while in exile.
The metal was reported as the causative agent in an outbreak of food-borne illness after a church gathering in which the coffee urn was apparently criminally contaminated with arsenic. This highlights the need for an index of suspicion when multiple individuals present to an emergency department temporally related and with similar symptoms and circumstances.
Arsenic is typically considered a heavy metal and shares many toxic characteristics with the other heavy metals (eg, lead, mercury). Arsenic is ubiquitous in the environment. It ranks 20th in abundance in the earth's crust, 14th in seawater, and 12th in the human body. In nature, arsenic exists in the metallic state in 3 allotropic forms (alpha or yellow, beta or black, gamma or grey) and several ionic forms.
Arsenic has been used as a medicinal agent, a pigment, a pesticide, and an agent of criminal intent. In the form of chromated copper arsenate (CCA), it was used until recently as part of the treatment to render architectural wood immune to pest infestation. This product was banned for use in the United States by the Environmental Protection Agency (EPA) in 2003. A great deal of the treated wood continues to exist in the form of decks and other structures exposed to the elements. Data suggest that a significant quantity of arsenic may leach out from such wood into landfills and into the interiors of homes with existing CCA-treated decks.[4, 5, 6] The durability of the CCA-treated wood suggests that such exposures may continue for decades. There is evidence in the rodent model that exposure to this compound, CCA, may produce significant renal pathology. Today, arsenic is primarily used in the production of glass and semiconductors.
Arsenic may be found as a water or food contaminant, particularly in shellfish and other seafood, and often contaminates fruits and vegetables, particularly rice.
Today, arsenic poisoning occurs through industrial exposure, from contaminated wine or moonshine, or because of malicious intent. The possibility of heavy metal contamination of herbal preparations and so-called nutritional supplements must also be considered. There has been a resurgence of interest in arsenic as a medicinal agent for treatment of acute promyelocytic leukemias, multiple myeloma, myelodysplastic syndromes, and assorted resistant solid tumors.
An association between exposure to arsenic and the development of Alzheimer disease has been proposed. In addition, an apparent link exists between arsenic exposure and gestational diabetes and potential long-term effects on the infants born to mothers consuming arsenic-contaminated water among other during pregnancy.[8, 9]
Because arsenic has been involved in geopolitics, an estimated 100 million people are at risk of exposure to unacceptable arsenic levels in either well water or ground water. Numerous "outbreaks" of excessive arsenic in water and food from an assortment of natural and anthropological causes have occurred. This has become a major public health issue in the developing world, primarily Bangladesh and surrounding countries, where many thousands of individuals have precancerous arsenic-related disease.
Inorganic forms of arsenic are more toxic than organic forms. The trivalent forms are more toxic and react with thiol groups, while the pentavalent forms are less toxic but uncouple oxidative phosphorylation. Very few organ systems escape the toxic effects of arsenic.
Trivalent inorganic arsenic inhibits pyruvate dehydrogenase by binding to the sulfhydryl groups of dihydrolipoamide. Consequently, conversion of pyruvate to acetyl coenzyme A (CoA) is decreased, citric acid cycle activity is decreased, and production of cellular ATP is decreased. Trivalent arsenic inhibits numerous other cellular enzymes through sulfhydryl group binding. Trivalent arsenic inhibits cellular glucose uptake, gluconeogenesis, fatty acid oxidation, and further production of acetyl CoA; it also blocks the production of glutathione, which prevents cellular oxidative damage.
Effects of pentavalent inorganic arsenic occur partially because of its transformation to trivalent arsenic; toxicity proceeds as outlined above. More importantly, pentavalent arsenic resembles inorganic phosphate and substitutes for phosphate in glycolytic and cellular respiration pathways. Consequently, high-energy phosphate bonds are not made, and uncoupling of oxidative phosphorylation occurs. For example, in the presence of pentavalent arsenic, adenosine diphosphate (ADP) forms ADP-arsenate instead of ATP; the high-energy phosphate bonds of ATP are lost.
Arsenic has been shown to produce oxidative stress. In a small pilot study of environmentally exposed children, arsenic altered monocyte superoxide anion production and inhibited nitric oxide production.
Arsenic trioxide has been shown to cause a significant prolongation of cardiac action potential duration at many levels of repolarization producing conduction delay and increased triangulation. Electrolyte imbalance appears to enhance this toxicity. The drug appears to inactivate endothelial nitric oxide synthase, leading to a reduction in production and bioavailability of nitric oxide. It also has been associated with inducing/accelerating atherosclerosis, increasing platelet aggregation and reducing fibrinolysis.
Arsenic is listed as a presumed carcinogenic substance based on the increased prevalence of lung and skin cancer observed in human populations with multiple exposures (primarily through industrial inhalation).
According to the American Association of Poison Control Centers' (AAPCC) National Poisoning Data System (NPDS), in 2010, there were 927 human exposures related to arsenic (excluding pesticides) and 67 exposures related to arsenic-containing pesticides. The majority of the pesticide exposures occurred in children younger than 5 years (43 [65%] of 67), whereas more than 58% of the nonpesticide exposures occurred in adults (539 of 927).
Worldwide, up to 100 million people are at risk of exposure to arsenic from excessive arsenic in drinking water. In Bangladesh, more than 95% of the water supply to over 138 million people is potentially arsenic contaminated at levels exceeding the US EPA and WHO action limits. If international efforts at elimination of the risk are unsuccessful, it is estimated that a substantial proportion of the Bangladesh population will develop arsenic-related diseases such as pulmonary and skin cancers as well as cardiovascular and renal disease.
In addition to the concentration of arsenic in the water, the prevailing diet existing in the affected areas may place the citizens at increased risk for toxicity from the arsenic. The population was recently surveyed and those individuals who had diets deficient in certain B vitamins and antioxidants appeared to have greater risk of arsenic dermatoses. An inverse correlation was found between consumption of vitamins A, C, and E, riboflavin and folic acid, and the existence of dermatological manifestations or chronic arsenic exposure.
According to the American Association of Poison Control Centers' (AAPCC) National Poisoning Data System (NPDS), 6 individuals suffered major effects and 3 died from exposure to nonpesticide arsenic exposure in 2011. Two of the 3 deaths were the result of suicides. There were no serious effects seen in the pesticide exposures.
Men are more likely to experience industrial arsenic exposure than women.
As in many reported cases of poisoning, the majority of reports of exposure to arsenic-containing pesticides occur with children younger than 6 years as the victim (274 of 379 in the NPDS 2007 data), whereas, when nonpesticide arsenic exposure is involved, the majority are in adults older than 19 years (645 of 1165).
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