It’s been a good year for rain in California, which means it's been a good year for mushrooms. Which also means it has not been a good year when it comes to mushroom poisonings.
Over just two weeks in December, the California Poison Control System logged 14 cases of death-cap mushroom poisonings in the northern half of the state, according to a report this month. Previously, it’s gotten only a few a year. The death cap (Amanita phalloides), which is native to Europe, is one of the most poisonous mushrooms in the world. Three of the victims required liver transplants. One of them, an 18-month-year-old girl, suffered permanent brain damage.
But this recent spate of poisonings may also have something to teach doctors: Some of these cases add to data points in a long-running clinical trial for a drug to treat death-cap poisoning.
The trial is run out of Dominican Hospital in Santa Cruz, California, which is an unusual place to host a national clinical trial. Dominican is a community hospital, not affiliated with a university or research center. And Todd Mitchell, who runs the clinical trial, is a doctor there with a background in family medicine. Yet through a twist of fate, he has become of the nation’s experts on the poison in death-cap mushroom, also known as amatoxin.
It all began in January 2007, when a family of six showed up at Dominican Hospital vomiting and with diarrhea. They had recently eaten tacos made with mushrooms foraged in a state park. (Death caps can resemble non-toxic mushrooms, and perversely, they are said to be delicious.) Mitchell was one of the doctors on call that day. “Amatoxin poisoning is a sort of thing if you’re treating a case, it’s probably your first and last case you’re ever going to see in the course of a career,” he says. Mitchell had never treated a case before, and now he had six on his hands.
So Mitchell turned to Google. He quickly found that an intravenous drug called silibinin, an extract from the milk thistle plant, is used in Europe to treat amatoxin poisoning. Silibinin has not been approved in the U.S., so Mitchell had to get emergency one-time permission to use the drug from the Food and Drug Administration. The drug had to be shipped from Germany. About three days after the family got poisoned, they got the silibinin. Five of the patients eventually recovered. The 83-year-old grandmother died of kidney failure, though her liver was starting to recover after the silibinin treatment.
Mitchell thinks silibinin works by blocking amatoxin from penetrating liver cells. The drug alone, he says, is not enough: People who are poisoned suffer severe dehydration from all the vomiting and diarrhea, which can cause kidney damage. Mitchell says patients might initially need four to seven liters of IV fluids to compensate.
Eventually, Mitchell got the FDA on board to do a proper clinical trial for silibinin that could get the drug approved in the U.S. That trial began in 2009 and is still going. Dominican Hospital’s pharmacy stocks the drug and sends it out to hospitals wherever poisoning patients might show up. A total of 97 patients have been treated with it.
Several, though not all, of the 14 people poisoned in Northern California in December were given silibinin. Kathy Vo, a medical toxicologist who co-authored the recent report, works for the California Poison Control System, which doctors can consult for advice. Because silibinin is still unproven, the CPCS presents the drug as one of several options, including using IV fluids alone. It’s tough to run clinical trials on poisons, because you can’t exactly randomly assign patients to get an antidote or not. “We would like to see a clear therapeutic benefit, at least as clear as possible,” says Vo. “The more patients, the better.”
When Mitchell treated his first patients with silibinin in 2007, the drug was made by a company called Madaus. That company was bought by Rottapharm, which was bought by Meda, which was bought by Mylan. It's now up to Mylan to get silibinin approved in the U.S. The company did not respond to a request for comment about the drug though, and the only mention of silibinin or its brand name, Legalon, on Mylan’s website are in documents and filings for its acquisition of Meda.
But Mitchell is pushing ahead in other ways. He’s traveled to China, where mushroom poisonings in the Yunnan province are especially common, to help set up a pilot program for silibinin there. He’s also working with vets on a protocol for dogs who have eaten death caps. You can teach people to avoid death caps, he says, but dogs are another story.
So for the humans: Death caps can vary in appearance, but they have gills and usually yellow-green caps. Watch out.
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