It was a stormy Midwestern evening when Ms. Orpiment arrived in hospital transfer from Olds Lake, Minnesota. The sky was black with streaks of yellow and gray as the lightning flashed. The tornado sirens let out a plaintive wail, like mechanical banshees filling the air with dread.
Our patient, a 65-year-old woman, had a one-year history of stocking and glove paresthesias. It had recently progressed to lower extremity weakness, burning neuralgia in her feet, and intermittent bowel and bladder incontinence. The outside diagnosis was Guillain-Barré syndrome, but the story did not fit. Another record mentioned an elevated arsenic level in her urine. She had been recently treated for giardia with a 10-day course of metronidazole, but otherwise had an unremarkable medical history. She worked in a factory making batteries, and was in the midst of a bitter divorce. Could this be arsenic poisoning?
In the play and film Arsenic and Old Lace, the Brewster sisters used arsenic for therapeutic murder, an aggressive form of palliative care for lonely old men. Once the men were deceased, the sisters' deluded nephew, Teddy, buried the “victims of yellow fever” in their basement.
Arsenic is tasteless, odorless and readily available, making it one of history's most popular poisons. However, unlike in the fictional play, victims do not always shed their mortal coil peacefully. Acute arsenic toxicity leads to nausea, vomiting, severe abdominal pain and rice water diarrhea, soon followed by cardiovascular instability and death. In the past, sufferers were frequently misdiagnosed—not with yellow fever, but with cholera, which as a frequent epidemic provided excellent cover for nefarious acts.
Use of arsenic as poison reached its peak in the Renaissance. In Italy, the Medici women were famous for eliminating husbands with aqua tofana, and in France impatient heirs would lend death a hand with poudre de succession, or “inheritance powder.” Post-mortem tests for arsenic, developed in the 19th century, led to the end of common usage. However, cases still occur, such as the 2003 mass poisoning of parishioners in New Sweden, Maine, with spiked coffee.
Since cholera seemed less likely in our patient's case, we considered chronic exposure to arsenic. Long-term exposure has multi-system effects, the most notable being neurological and dermatological. Neurologically, it causes a symmetrical sensorimotor neuropathy, with stocking and glove distribution anesthesia, paresthesia or hypesthesias, followed by distal weakness. Dermatologically, it can cause patches of hyperpigmentation, hypopigmentation (raindrop lesions) and hyperkeratoses. Along with heavy metals, it can cause Mees' lines—horizontal white lines on the fingernails.
Our patient's neurological symptoms fit, so what could be the source? In the 19th century, arsenic exposure was endemic. Arsenic pigments, including emerald green, were prized for their vibrant shade, and were found in everything from wallpaper to cheap hooch. Strangely, society eventually opted for subpar hues over poisoning, and now toxic arsenic exposure is relatively infrequent. Occupational exposure does still occur on occasion, though, and since our patient's work included soldering circuit boards, it was possible she was exposed to tainted fumes. Her hometown relied on well water, which the U.S. Environmental Protection Agency classifies as safe with arsenic levels below 10 mcg/L.
We sat in the hospital cafeteria, eating our usual gourmet lunch and mulling over our patient's condition. Our stomachs growling, our thoughts turned to seafood. While mercury may get the glory as the toxin associated with fish, seafood can contain large amounts of arsenic, up to 100 mg/kg, versus less than 250 mcg/kg found in most other foods. A fish dinner from a fast food restaurant can spike urine arsenic levels into the 1000s. Luckily for sushi fans everywhere, arsenic in fish exists as mostly organic species, which are relatively harmless and rapidly excreted in the urine.
And that brings us back to our patient. Upon further evaluation, speciation of her urine arsenic revealed it was arsenobentane—an organic, non-toxic form. There had been no intentional poisoning by her spouse, no occupational exposure. She hadn't been rubbing arsenic on her face to create a healthy complexion, or sipping knock-off absinthe. No, her condition arose innocently, from her love of seafood. The correct diagnosis? Metronidazole-induced peripheral neuropathy. The arsenic had merely been a red herring.