The Poisoner’s Poison
Do you want to know which substance is so toxic it’s called the poisoner’s poison? What pigment used in painting is used to treat this toxin? And which antidote contains cyanide? Listen to find out more.
This is the pick your poison podcast. I’m your host Dr. JP and I’m here to share my passion for poisons in this interactive show. Will our patients survive this podcast? It’s up to you and the choices you make.
Want to know what substance is so toxic it’s called the poisoner’s poison? Which antidote contains cyanide? What pigment used in painting is also used as an antidote? Then stay tuned.
Today’s interactive episode starts in the ER where you’re working a shift, when you hear an ear-piercing scream of pain. You look up to see the nurse draping a sheet over the legs of a 22-year-old woman. At the sound, the nurse whips the sheet off, revealing the patient’s completely normal looking legs. No obvious signs of trauma, wounds or infection. The patient stops screaming but looks very uncomfortable and continues to cry.
What is going on here? Why is she screaming? Is the woman suffering from psychiatric illness? Other than her drastic reaction to the bedsheet, her behavior seems appropriate. The nurse says the patient is complaining of severe pain in her legs. She’s also had some vomiting and abdominal pain.
Her physical examination is unrevealing. Her vital signs are normal, her abdomen is nontender. She screams again when you touch her legs to check the pulse. The pulses are normal, she can move the legs normally and there’s no redness, swelling, rash or any other findings.
Why then is she screaming about the featherweight of a bedsheet on her normal looking legs? The medical term for this is pain out of proportion to exam. It describes a patient who reports excruciating pain, but doesn’t show exam findings, making diagnosis difficult.
Classic diseases that cause pain out of proportion are ischemia, lack of arterial circulation, but the strong pulses in her feet rule that out. Infection in the deep tissues can cause it, but this doesn’t spontaneously occur in young healthy patients, and in any case wouldn’t happen in both legs at once.
This is a poison podcast – so what are the toxicological causes of pain out of proportion? Black widow spider envenomation causes significant pain and only two tiny puncture wounds. But it causes pain all over, not just in the legs. Hydrofluoric acid is a classic cause of pain out of proportion in toxicology. It’s used to clean bricks and is also found in wheel cleaner. Patients can get severe pain before burns develop. Usually, it’s in the hands for obvious reasons. She hasn’t been bitten by a spider and denies exposure to any chemicals. Neuropathy causes severe pain. Toxins, like chemo, are definite causes. But it’s rare in an otherwise healthy person, and typically doesn’t develop suddenly over the course of a few hours, like this.
She visibly uncomfortable. In fact, she screams even with the slightest movement of a single hair follicle on her legs. The nurse lets a visitor back, the patient’s roommate. She sits in a chair with a hand on her abdomen. She hikes her skirt up so it rests above her knees.
She’s not feeling well either, reporting diarrhea. She also has pain in her legs. It’s not as severe as the patient’s but she reports it’s getting worse.
What is going on here?? Is there something in the apartment? Carbon monoxide is a common environmental exposure, but it causes headaches and dizziness, not excruciating pain. Pesticides are toxic, many are lethal, but don’t cause severe pain in the legs, at least not without a constellation of life-threatening symptoms. The visitor checks her phone and tells you a third roommate has abdominal pain and leg pain.
This has to be a poison. All three roommates, previously healthy, now have the same symptoms. We need to double down on the potential causes. Reviewing what we know, not much, but there is a recognizable pattern. Gastrointestinal symptoms and nervous system symptoms.
Question #1 – The association of neurological plus gastrointestinal symptoms suggests what poison?
A. Carbon monoxide poisoning
B. Radiation
C. Cyanide
D. Heavy metals
Answer: D Heavy metal poisoning.
We still don’t know the cause—heavy metals include lead, mercury, arsenic and cadmium. And of course just because they have this classic pattern, it doesn’t rule out other types of poisons.
Since we have nothing else to go one, let’s focus on heavy metals for now. The roommates are all students, no one works with heavy metals or has a hobby like jewelry or stained glass making where they might’ve been exposed. Heavy metals can be found in supplements, spices and cosmetics imported into the US. For example, lead in spices, mercury herbal supplements and skin lightening creams crems just to give a few examples. They deny exposure to products from outside the US.
We assume this is a malicious, rather than accidental poisoning. The patient is now receiving morphine. Despite hefty doses, she is still having pain. The roommate reports one unexpected event. The patient received a box of chocolates from an unknown source. They were in a fancy box from an expensive chocolatier. The patient ate one. The two roommates split a second one.
The taste and appearance of the fancy chocolates was unexpected. The chocolate tasted funny. The roommate says the pain in her legs is now too much to tolerate and she wants to check in as a patient for pain medicine.
The roommate thinks they are still in the trashcan and texts her mother, asking her to see if she can retrieve them and bring them to the hospital. She signs in. The triage nurse puts her in the room next door to your first patient. You order morphine for her now excruciating pain.
Arsenic is always at the top of the list for malicious poisoning. It has a long history of use in poisoning. It definitely causes gastrointestinal symptoms, abdominal pain, vomiting and diarrhea. Its been used for murder since the middle ages. It was hard to detect in those days because the symptoms resembled cholera, a diarrheal illness. It has a long history of use poisoning spouses. Arsenic does cause neuropathy, but typically it takes weeks to develop. And while painful, this level of excruciating pain is not typical either. While we can’t exclude arsenic, it doesn’t quite fit. Lead poisoning can cause painful extremities, but again, symptoms typically occur over weeks, not suddenly. Other heavy metals include cadmium, chromium, manganese, zinc and nickle. Exposure to these metals is occupational, and the symptoms. Don’t fit. Mercury can be found of course in thermometers and also in older thermostats. But again, hard to imagine how this would be an occult exposure and the symptoms just don’t match.
There is one toxin that notoriously causes excruciating pain. Its also been called the “poisoners’ poison”.
Question # 2 What is it?
A. Copper
B. Thallium
C. Cyanide
D. Botulism
Answer: Thallium.
Thallium has been called the poisoner’s poison in part because of the excruciating pain it causes. In part because its lethal, but slow. In addition, it’s difficult to test for and one of the classic physical exam findings is delayed by several weeks. So, thallium has been called the poisoners poison. Several prominent toxicologists whose names I won’t mention here have suggested if they were to choose a poison for their worst enemy it would be thallium. Why because it’s definitely lethal. Thallotoxicosis difficult to diagnose and it causes excruciating pain before it kills you.
These properties of thallium were exploited by Saddam Hussein. Thallium can cause death, it often does so in a delayed fashion. The patient becomes comatose and paralysis of the diaphragm causes them to stop breathing. Some reports tell of released prisoners given a “last drink” with the jailer. Literally. Unbeknownst to them, the drink contained thallium. The person then died after immigrating to another country, believing they were safe. Iraq wasn’t the only government using thallium on its enemies. More on that later in this podcast.
Back to our patient. We can test for heavy metals in the urine, but the results will take at least three days, if we are lucky, almost no hospital lab can run these tests and most specimens will have to be sent to an outside lab for analysis which adds another few days to the results. We send the urine out. What should we do in the meantime?
We suspect poisoning, but we have no forthcoming information. What about the box of chocolates? The patient’s mother brings in the box. We can arrange for testing, but that will take time, longer than urine testing, weeks if we’re lucky. Two chocolates are missing per the history. The rest of the chocolates are still in the box. They don’t look like chocolate designed by the famous chocolatier whose box they are in. Their lumpy, there misshapen, there is regularly shaped some are much larger than others, there cracked. These are not fancy chocolates. They look like dough balls that have been padded into irregular shapes. They’re more like a failed home cooking experiment.
In toxicology definitive lab tests often take a long time to result. Therefore toxicologists are used to relying on ancillary information and clinical exam findings to both figure out what the toxin might be and to direct use of treatment methods or antidotes. In this case suspecting thallium poisoning, there are two things we could try to help confirm our diagnosis. One is a test we could do with a specimen from the patient and one a test we could do on these unusual looking chocolates.
First, we could test the patient’s hair. Now this isn’t hair analysis like you might have heard about. Analyzing the presence of thallium in the hair can be useful in documenting thallium exposure. But hair testing usually takes weeks, even longer than blood and urine testing. It might be useful for an investigation or documentation, but it won’t be helpful clinically, to treat the patient now. What I’m referring to is a quick and dirty test. You ask the patient if you can pull out a strand of hair—at the root. Then you take it down to the lab and ask to borrow microscope. If the hair follicle contains black pigmentation at the base, it might confirm our suspicion.
Second, there’s another quick test we can do with the chocolates. As I’m sure you know, metal is very bright on extra is why we can see coins people swallowed. So you take the chocolates to the x-ray department, ask the radiologist for a big favor. You might even include a candy bar from the hospital vending machine next to the misshapen chocolates as a control. Thallium, as a metal, should show up very bright. You do in fact see that the suspicious chocolates light up extremely bright. Like something containing a metal and not at all like the regular candy bar from the vending machine.
Our focus on the symptoms and list of potential toxins is productive. One of it’s appeals to criminals is difficult to diagnosis and often missed until a tell-tale sign shows up later.
At this point, our suspicion for thallium poisoning is high. It’s our presumptive diagnosis. In a few days, we’ll have the test results.
Should we wait for the test results or start treatment now? To decide, let’s consider the potential treatment options. Just like our antidote in episode 1, we need to weigh the risks and benefits of treatment. The patients are worsening, the potential exposure could be lethal and we won’t have a definitive answer for several days.
What is the treatment for thallium toxicity?
A. Charcoal
B. A pigment used in painting
C. Dialysis
D. all of the above
Answer: All of the above.
First: Activated charcoal. Yep, charcoal but not in a brisket like you might use to grill but rather in a liquid form. We toxicologists love it so much we used to recommend it for all poisonings. Why? Charcoal binds to many drugs and toxins, inactivating them, allowing it to pass through your gastrointestinal tract and out into the toilet without being absorbed into your bloodstream.
Now we reserve it for certain circumstances, because it’s generally useful for toxins still in the stomach since it doesn’t work as well lower down in the digestive tract. A few drugs are recycled in a loop between the liver and the small intestine. In these cases, we use multi-dose activated charcoal to break up this cycle and eliminate the drug.
Question number 2. Which pigment used in painting is an antidote for thallium?
A. Cinnabar = mercury sulfide
B. Emerald green = Arsenic
C. Prussian Blue
D. Cochineal = beetles
E. Naples Yellow = Lead
Second: Prussian blue pigment, used by painters. Including one of the most famous examples van Gogh’s Starry night. See Episode 1 for more toxicologic associations with that painting. How does a pigment treat poisoning? Like charcoal, it binds thallium, in this case exchanging it for potassium. It shortens the lifespan of the thallium in the bloodstream and reduces concentrations in the heart and brain.
Prussian blue is sold under the trade-name Radiogardase in the United States. That’s because it’s also used to treat radioactive cesium poisoning.
Third: Dialysis. Dialysis eliminates the naturally occurring waste and toxins that build up in renal failure. It can also remove some drugs. Is it useful for thallium? A small amount of thallium is removed.
Should be treat our patient? Wait? Treat. Ok, with which treatments? This is the reason medicine is an art, not a science. Like physicians do everyday, we need to weigh the risks against the benefits. Risk of charcoal? Minimal. It’s bad for the lungs, causes pneumonitis, but as long as the patient isn’t sleepy or lethargic and doesn’t choke on it—safe. If the bowel aren’t moving, it can cause a blockage, a very minimal risk in this case with a healthy patient.
The side effects of Prussian blue? Blue poop. That’s about it.
In this case I would start activated charcoal and Prussian blue. Other than the terrible taste of charcoal and blue poop, which we might not even get to see because charcoal causes black poop, there is little downside.
The decision to start dialysis is much more difficult. There are real risks associated with dialysis, infection being the biggest one. This very real risk would particularly be problematic if there was later found to be no benefit. Thallium is removed by dialysis—a small amount-- but many other toxins are not. Each patient will be different, but in this case I probably would wait to start dialysis until I at least had some preliminary lab testing.
Rather than twiddling our fingers while waiting for the results, let’s talk about the mechanism of thallium toxicity.
The honest answer: no one knows for sure.
It probably has the following effects. 1. Energy failure inside the cells by interfereing with ATP and the electron transport chain. 2. Interference with potassium metabolism, which is also critical for cell functioning. 3. Nerve damage. Nerves are covered in a protective sheath called myelin. Thallium damages the myelin in a dying back pattern which is pretty much as bad as it sounds. For unknown reasons, it has an affinity for long nerve fibers. This is why the symptoms start in the feet and progress upwards. 4. It damages disulfide bonds found in hair and nails. More on the delayed symptoms this causes in a few minutes.
Detour to today’s pop culture consult – what spy movie villain is poisoned by Thallium?
Mr. White in the James Bond movie Spectre is slowly dying of thallium poisoning apparenty poisoned by thallium placed on his phone. From a scientific standpoint, there are some sketchy elemets. Maybe I’ll do an episode entitled Fact or Fiction : Toxicology in books and movies. Operas… but I digress. Back to our patient.
Three days after the patient is admitted to the hospital, we finally get some results back. The spot urine test comes back with a thallium concentration of 10,000 µg/L. The normal value is less than 10. This is massively high level confirms our suspicion. Our patients have thallotoxicosis.
Since the level is astronomically high, I’d reconsider the risks and benefits of dialysis and call nephrology. Even removing a small amount of thallium might be beneficial here.
A few days later, the patient’s hair starts falling out. You notice she’s losing her eyebrows too. The findings of hair loss, alopecia, and severe pain in the legs are classic findings for thallium poisoning. Alopecia doesn’t develop for at least a week or two after exposure, one of the reasons diagnosis can be delayed. Strangely, thallium causes loss of the eyebrows, but unlike most other causes, spares the inner third of the eyebrows. It’s so classic, its almost diagnostic in and of itself.
Alopecia is caused, at least in part, by its effect on the disulfide bonds I mentioned earlier. Those effects also cause changes in the fingernails—Mee’s lines. White stripes across the nails. Mee’s lines aren’t specific to thallium, they can be seen in a number of different heavy metal exposures.
The history of thallium’s use in poisoning is fascinating. I could talk about it for hours, but you probably don’t have all day, so for the sake of brevity I’ll just hit some highlights. In Australia in the 1950s there was an episode called the “Thallium craze” where thallium became a popular method with housewives poison their husbands and other family members. Australian housewife and serial killer Caroline Grills, prison nickname, “Aunt Thally” poisoned numerous members of her family. Another woman expressed a wish to give her husband “a headache to repay the many headaches he had given me” referring, sadly, to domestic violence. In India it’s been called the inheritance powder.
It's not limited to unhappy housewives. Saddam Hussein I already mentioned. Other governments have used it—it was used for chemical warfare in the Rhodesian Bush War. The East German secret police used it to poison dissidents. Sidney Gottlieb of the CAI, famous for his unethical LSD experiments, reportedly suggested using it on Castro to cause his iconic beard to fall out.
It also has a long history of commercial use. It’s an effective rodenticide and the star of a famous ad campaign in the 1920s in a product called Rough on Rats, spawning several songs of the same title.
Disturbingly it was also used to treat humans with such advertising as Rough on Toothaches, Rough on Corns, Rough on Itching and Rough on Piles i.e. hemorrhoids. It’s questionable which it was rougher on the disease or the patients. Like almost every other pharmaceutical was advertised to as a treatment for syphilis and tuberculosis.
It was sold for cosmetic use as a depilatory cream called, I’m probably mispronouncing this Koremlu. It did remove unwanted hair. Unfortunately, at the painful cost of thallium toxicity.
Thallium was banned for use as a pesticide in 1972 in the US, but it’s use continued in other places. In Guyana in 1987, forty-four deaths occurred as a result of thallium toxicity in a poisoned food chain. Molasses laced thallium was intended to poison sugar cane rats. Cows ate the molasses. Thallium was excreted into their milk and killed many of the humans who drank the milk. This is a terrible, but illuminating case, about easily food chain contamination can occur.
Thallium has been reported since at least the 1980s as a contaminant and illicit drugs including cocaine, heroin, and opium. If you needed a good reason to avoid illicit drugs, here’s one more.
So what happened to our patients? Their hair fell out, as did their eyebrows. They suffered from a painful neuropathy. The first patient with the higher exposure for several months, the second for several weeks. The third roommate had symptoms which were milder and he never sought medical care. Thanks to our treatment, they both survived. Eventually their hair grew back.
If patients survive poisoning, many recover, but changes to the brain and nerves can be permanent. About 20% of patients, we estimate, develop residual nerve pain or residual neurocognitive defects. Meaning their brain doesn’t quite go back to where it started.
With a moniker like the poisoner’s poison, thallium has been used in books and movies other than James Bond films. Spoiler alert ahead. Thallotoxicosis is detailed in Agatha Christie’s novel The Pale Horse. I’m a strong believer that reading is a lifesaver in general, this book became a literal lifesaver. A little girl in an ICU was critically ill with an illness that stumped her doctors. The nurse sitting at her bedside, reading the book, recognized the symptoms of thallium poisoning, later confirmed by lab testing.
I hope our patient survived your choices today. This brings us to the last question in today’s interactive podcast.
What antidote contains cyanide?
a. MDAC
b. Prussian Blue
c. CroFab Rattlesnake antivenom
d. D. Naloxone (Narcan)
Post your answers on our Twitter feed @pickpoison1. I’ll post the answer in the next 24 hours.
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Remember while I’m a real doctor this podcast is fictional and meant for entertainment and educational purposes not medical advice. If you have a medical problem, please see your primary care practitioner. Thank you. Until next time, take care and stay safe.