Clinical Approaches to the Treatment of Chronic Arsenic Intoxication: From Chelation to Chemoprevention

Publisher Summary The dimercapto chelating agent, dimercaprol (British Anti-Lewisite, BAL) was developed in the 1940s as a treatment for acute poisoning by the vesicant organoarsenical chemical warfare agent, lewisite (dichloro [2-chlorovinyl] arsine). Water soluble analogs of dimercaprol, dimercaptosuccinic acid (DMSA, succimer), and dimercaptopropanesulfonic acid (DMPS, Unithiol, Dimaval) were introduced in the 1950s as chelators of arsenic (As) and other heavy metals that offered the advantage of higher therapeutic index, and both oral and intravenous routes of administration. Animal models have demonstrated that BAL, DMSA, and DMPS are efficacious in averting morbility and mortality if administered within minutes to hours of acute As exposure. In patients with chronic As exposure, administration of the chelating agents may result in a transient increase in urinary As excretion. However, the ability of chelation to avert or reverse the clinical effects of chronic As intoxication, such as anemia, neuropathy, portal hypertension or hyperkeratoses, or to decrease the future risk of As-induced cancer, has not been established. Limited case series, supported by recent insights into the potential mechanisms of As-induced carcinogenesis, suggest that oral treatment with retinoids, (Vitamin A analogs), may have promise in the treatment of chronic cutaneous arsenicism, and may also have impact on the development of neoplasia. Selenium, an antioxidant nutrient that antagonizes many of the effects of As in biological systems, also merits attention as a potential therapeutic agent for patients with a history of chronic As exposure. Nonspecific supportive care, including tricyclic antidepressants for the painful dysesthesias of peripheral neuropathy, and topical keratolytics for palmar–plantar hyperkeratoses, may offer short-term symptomatic relief.