Dr. Pulley of the University of Florida, Jacksonville, received honorariums from Argenx, Bio Products Laboratories, Catalyst, CSL Behring, and Stealth BioTherapeutics for consulting work.)
Dr. Weimer of Columbia University has received consulting fees from Roche.)
Arsenic toxicity has predominately been the result of suicidal or homicidal ingestion of massive quantities of arsenic. However, in India and Taiwan, the presence of arsenic in drinking water has made the problem endemic. In this article, the authors discuss the clinical manifestations, diagnosis, and management of acute and chronic arsenic poisoning. The focus of the article is on the effects of arsenic on the peripheral nervous system.
• Although arsenic is known more for intentional poisonings in homicides or suicides, arsenic toxicity is more common with occupational exposure or through drinking water in endemic areas.
• As with other heavy metal intoxications, the neuropathy related to arsenic is rarely seen without other systemic manifestations, including abdominal pain and skin changes.
• Arsenic neuropathy causes painful paresthesias and, with higher level or continued exposure, length-dependent weakness.
Historical note and terminology
Arsenic is a metallic compound known for its use as a poison in both homicide (Shumy et al 2016) and suicide attempts where the usual case is a massive acute exposure. However, toxicity can also result from chronic low-grade exposure. Occupational exposure may occur in the smelting of lead and copper ore (Feldman et al 1979), mining, and in the manufacture of integrated circuits or microchips. Other potential sources include contaminated well water (Kreiss et al 1983; Mukherjee et al 2003), tainted illicit drugs (Berger and Schaumburg 1996), arsenic-contaminated fossil fuels, high arsenic-containing coal (Liu et al 2002), or the burning of preserved wood (Peters et al 1986). Trivalent arsenate has greater human toxicity than pentavalent arsenate.
Reports have demonstrated that there is a large-scale problem in Bangladesh and India due to contamination of the groundwater, causing exposure to become endemic (Rahman et al 2001; Rahman et al 2005; Mukherjee et al 2003; Chakraborti et al 2016a; Chakraborti et al 2016b). In these areas a high proportion of individuals (10% to 20%) examined have evidence of arsenical toxicity. Of those with toxicity, peripheral neuropathy is a common finding (37% to 87%) (Rahman et al 2001). This group of patients represents the largest cohort reported to date with arsenic toxicity. Similarly, a report from Taiwan indicates that individuals living in areas that have ground water contamination are at markedly increased risk for abnormalities of nerve function (Tseng 2003).
Suspicions of arsenic poisoning have been advanced for a number of historical figures, including several United States presidents. Arsenic levels from exhumed remains of Zachary Taylor measured in 1991 were found to be insufficient to cause death. Arsenic was a treatment for a variety of disorders in earlier eras in various tonics and in Chinese herbs. It has been implicated in cases of traditional medication related toxicity in India (Valappil and Mammen 2019). Arsenic is still in use against acute promyelocytic leukemia, for which neuropathy has been reported as a complication (Shigeno et al 2005; Kuhn et al 2016).
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