Agency for Toxic Substances and Disease Registry
Case Studies in Environmental Medicine (CSEM) 

Arsenic Toxicity
Answers to Pretest and Challenge Questions

Pretest

1. See Challenge answer 4.
2. See Challenge answer 6.
3. See Challenge answer 10.

Challenge

1. The patient's drinking water, obtained from an artesian well, may contain elevated levels of arsenic due to leaching from natural mineral deposits in the surrounding bedrock. This phenomenon has been noted sporadically throughout the United States, including the Northwest. The patient's employment in carpentry and home construction may place him in contact with arsenic-containing wood preservatives used to treat lumber. Exposure may potentially occur percutaneously in the course of repeatedly handling moist, freshly treated lumber or via inhalation or ingestion of wood dust liberated during sawing. Ingestion or inhalation of ash or flue gas created during burning of arsenic-treated wood in his home fireplace or wood stove may also be a source of household arsenic exposure.
2. A sample of the patient's well water can be sent for arsenic analysis. Lists of qualified laboratories may be obtained from the county or state health department. The patient should be questioned about his use of arsenic-treated wood and wood preservatives; arsenic content may be listed on product containers or on Material Safety Data Sheets available from the supplier. The supplier should also indicate whether purchased lumber has been treated with arsenical wood preservatives. The patient should be questioned regarding how much well water he drinks on a daily basis, how often he burns construction scrap for heat in his home, and whether he uses arsenic-containing pesticides (including which ones and how often). In any case of suspected arsenic intoxication, the physician should consider the possibility of intentional poisoning and notify social agencies, if appropriate.
3. Because nontoxic trimethylated organic arsenic (arsenobetaine or arsenocholine) ingested in a seafood meal may markedly elevate total arsenic levels, the patient should be questioned about ingestion of seafood within the past 2 days. If seafood has been ingested, laboratory speciation of the urinary arsenic can rule out involvement of arsenobetaine or arsenocholine. However, given the patient's clinical presentation, exposure to toxic inorganic arsenic is likely.

   In this case, speciation reveals inorganic arsenic present at 1,700 µg/L, monomethyl arsonic acid at 2,200 µg/L, and dimethyl arsenic acid at 2,100 µg/L, confirming that the patient has sustained inorganic arsenic exposure. Since most laboratories do not provide speciation, an alternative approach to interpreting a high urinary arsenic concentration (>500 to 1,000 µg/L), if seafood ingestion is a possible factor, would be to repeat the measurement with a new urine sample 48 to 96 hours after complete avoidance of seafood. The trimethylated fish arsenic should be completely cleared by that time, but the metabolites of inorganic arsenic, which have slower clearance, should still be present at elevated levels.

4. The patient's problem list includes peripheral neuropathy, hyperpigmentation and hyperkeratotic skin lesions, macrocytic anemia, and liver transaminase elevation. The neurologic, dermatologic, and hematologic abnormalities are highly suggestive of chronic arsenic intoxication. The patient has a characteristic stocking-glove peripheral neuropathy, with predominantly painful sensory symptoms, but no apparent cranial nerve or central nervous system dysfunction. His skin displays hyperpigmentation and palmar-plantar hyperkeratoses characteristic of chronic arsenic ingestion. Consistent laboratory findings include a CBC and peripheral blood smear displaying macrocytic anemia, relative eosinophilia, and occasional basophilic stippling, and a chemistry panel revealing slight elevation in liver transaminases.
5. Guillain-Barré syndrome is a primarily motor neuropathy that may begin shortly after a viral infection or immunization. Although the patient's neurologic complaints began 1 month after a flulike illness, examination failed to reveal the characteristic rapid tempo and motor predominance of Guillain-Barré syndrome. Chronic alcoholism may be associated with sensorimotor peripheral neuropathy, macrocytic anemia, and liver transaminase elevation, but cerebellar ataxia and other findings such as hepatomegaly and telangiectasia are usually also present with alcoholism. Thallium intoxication may also result in a sensorimotor peripheral neuropathy. Other diagnostic considerations include paraneoplastic syndromes, particularly those associated with lung cancer, diabetes mellitus, and certain chronic inflammatory neuropathies.
6. The patient's urine should be screened for the presence of arsenic and thallium using either a 24-hour urine collection or a first void morning specimen. A chest radiograph should be examined for occult malignancy. Neurologist referral for electromyography and nerve conduction studies may be useful to further characterize the peripheral neuropathy and to establish an objective baseline for follow-up measurement. Dermatologist assessment of the patient's skin lesions, possibly including skin biopsy, is indicated to evaluate for cancer or to characterize a precancerous state. The possibility of diabetes mellitus can be investigated by measuring a fasting blood glucose and urine dipstick for glucose and ketones.
7. Arsenic-induced skin changes generally result from chronic arsenic exposure and have a latency of several years. Hyperpigmentation typically precedes hyperkeratoses, which in turn precede dermal neoplasms. The presence of both hyperpigmentation and palmar-plantar keratoses in the patient suggests that his arsenic exposure began at least 3 years ago, before consumption of drinking water from his current well. Since he resided on a nearby property for 10 years, the well at that location should also be suspected of containing high levels of arsenic.
8. The patient's wife, who resides with the patient and may consume the same well water, is at risk for chronic arsenic poisoning. Residents in the surrounding geographical area, who may also be obtaining water from artesian wells, should be considered at risk. Former area residents who consumed arsenic chronically before moving away constitute a third group potentially at risk for delayed development of arsenic-associated disease.
9. A careful history reveals that the wife, unlike the patient, consumed the well water infrequently, preferring instead to drink bottled water, soft drinks, and juices. Before moving in with her husband 10 months ago, she resided in a metropolitan area geographically remote from the present site, where the water was not obtained from wells. Thus, because her arsenic ingestion was markedly lower and of shorter duration than her husband's, she has not yet developed signs or symptoms of chronic arsenic intoxication.

   Both the patient and his wife use the arsenic-containing well water for showers and baths. The substantial amount of arsenic in the wife's hair likely reflects external contamination from this source. The arsenic content of the husband's hair is elevated from a combination of external contamination and internal incorporation into the growing hair. The relative contribution from endogenous and exogenous sources cannot be distinguished through bulk hair analysis.

10. Immediate cessation of consumption of arsenic-containing well water is the essential first step. The patient must stop using treated wood for heating and cooking in the home, and must be protected from such exposures in the workplace. Gloves should be worn whenever arsenic-treated wood is handled, and respiratory protection should be used when sawing this wood. Because the utility of chelating agents in reversing or improving the patient's arsenic-related peripheral neuropathy, anemia, and palmar-plantar keratoses has not been established, chelation treatment cannot be routinely recommended. Analgesics and/or certain tricyclic antidepressants have been reported to be beneficial for the painful dysesthesias associated with peripheral neuropathies. Because some reports indicate that vitamin A analogs (retinoids) may be valuable in the treatment of precancerous arsenical keratoses, referral to a dermatologist for consideration of this treatment is indicated. The patient will remain at risk for the delayed appearance of arsenic-related skin cancer and merits regular, long-term dermatologic follow-up.
11. Because of the likelihood that other wells in the area contain elevated levels of arsenic, public health intervention may be necessary to prevent additional cases of hazardous arsenic exposure.

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