Episode 81- “Bad Shrooms”: Part One: Amatoxin

Hello and welcome to Episode 81 of ER-Rx, a podcast tailored to your clinical needs. I’m your host, Adis Keric, and in this two-part series, I’ll be talking about poisonous mushrooms. This week, I’ll do a quick background about some of these mushrooms, focusing on amatoxin, then next time I’ll talk about treatment options.

Mushrooms that contain amatoxin are pretty rare but they’re a major cause of liver failure and are responsible for 95% of deaths from mushroom ingestions around the world. Amatoxin is usually found in the Amanita group of mushrooms, nicknamed the “deadly white Amanitas” (A. phalloides, A. virosa, A.verna, A. ocreata) with some pretty sick names like “Death Cap,” “Destroying Angel,” and the not-so-sick “Fool’s Mushroom.” But remember that not all Amanita group mushrooms contain the toxin, and that Amanita group mushroom aren’t the only ones that can contain the toxin. For example, other groups of mushrooms, like the Lepiota and Galerina groups can also carry it.

The classic patient is usually exposed to amatoxin by foraging for mushrooms- either to eat or to get high- and mistakes toxic mushrooms for edible ones. But this is still a relatively rare thing. Of the thousands of species of mushrooms, only somewhere between 50-100 are toxic to humans, and only about 35 mushrooms contain amatoxin. The scary thing about amatoxin is that it stays toxic whether you eat it raw or cook it, and to the rookie mushroom-hunter it can be very hard to tell apart dangerous shrooms from safe ones. Another scary thing is that it can be lethal in very small doses. The estimated lethal dose is 0.1 mg/kg or about 7 mg in adults- which is only about 1-2 medium-sized mushroom caps. The good news is that death from amatoxin is pretty rare- with 50 deaths per year in Europe and Asia and only a handful of deaths in the US.

Amatoxins are fascinating compounds. I should also clear up that the term “amatoxin” is an umbrella term for at least 9 related toxic compounds. Anyway, the mechanism by which all of these amatoxins cause damage is pretty complex, but in summary, amatoxins are rapidly absorbed from the intestine and sent to the liver by OATP (organic anion transporting polypeptide) transporters. Once in the liver, they cause irreparable damage by inhibiting RNA polymerase- which if you remember from biochem- hinders transcription of mRNA. Without mRNA, cell metabolism stops and apoptosis starts.

The liver is hit the hardest because it’s the first organ that amatoxin sees after absorption from the GI tract. But other organs that also have rapid cellular turnover, likes cells of the GI tract or the kidneys, are also affected.

Amanita toxicity happens in three phases. The first phase typically begins 6-24 hours after ingestion. Patients can feel nauseous and crampy and will have large amounts of watery and even bloody diarrhea. Massive fluid losses can lead to hypovolemia, acute kidney injury, and shock. In this phase, liver enzymes and bilirubin are typically normal.

The second phase, which starts around 24-36 hours after ingestion, is characterized by patients typically starting to feel a little better from a GI standpoint. During this phase, AST and ALT become elevated and peak 60-72 hours post-ingestion. In very severe poisonings, this phase can be skipped altogether and patients can go directly from phase one to phase three.

In the third phase, which happens about 48-96 hours after ingestion, both liver and renal function are severely diminished. Loss of liver function means patients can develop hypoglycemia, coagulopathy, hepato-renal syndrome, and hepatic encephalopathy and they can die within 3-7 days without proper support.

Diagnosis is mostly based on the history of delayed-onset GI symptoms or hepatoxicity after eating a mushroom. You can also try to identify the mushroom, but we shouldn’t wait for identification before providing treatment- and identification should only be attempted by an expert medical toxicologist—so obviously involved your tox team or poison control center immediately.

Treatment consists mostly of supportive care- and if treatment is started immediately, we can keep the mortality rate of these poisonings to < 5%. Some agents, like N-acetyl-cysteine, high-dose penicillin, cyclosporine, and silibinin can be attempted- but if it gets bad enough a liver transplant may be the only definitive treatment.

Next week, we’ll go over some of these treatments more in depth- with a useful guide on how to get silibinin- from personal experience.

As always, thank you so much for your time, and thank you for wanting to learn more about pharmacotherapy. If you have any comments or anything you’d like to add to this episode, please give me a shout out on the @errxpodcast Instagram page, or reach out to me on errxpodcast.com- I’d love to respond to all comments and criticisms.

I also want to take a second to shout out listener Li Sha for her very generous donation on BuyMeACoffee.com- donations like this keep the podcast running and free for everyone. I’ll see you next time.