In Summer, Fungi Emergencies Mushroom

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As Memorial Day ushers in the warm, humid days of summer, emergency department staff have to keep a watchful eye out for seemingly simple gastroenteritis cases that may actually be a much more harmful condition — mushroom toxicity.

Although rare, mushroom toxicity can lead to liver failure or death if not treated appropriately, and it may be cropping up in areas where it’s least expected, researchers say.

Last summer, for instance, four patients in the Washington, D.C. area were treated for mushroom poisoning over a 2-week period at MedStar Georgetown University Hospital (MGUH), Maiyen Tran Hawkins, DO, and colleagues reported at Digestive Disease Week in San Diego last week.

“Patients typically present with diarrhea, abdominal pain, nausea, maybe vomiting, and it sounds a lot like viral gastroenteritis,” Tran Hawkins told MedPage Today. “They go to the ER, and initially their blood work might be normal or maybe they just look a little dehydrated, so they get sent home.”

But after a brief period of what seems to be recovery, patients can fall into severe liver failure, she said.

“They come back [to the ER] jaundiced and not feeling well at all,” she said. “When it’s diagnosed, they likely have had significant liver damage.”

The first of the four patients treated at MGUH arrived on Sept. 12, 2011 with complaints of diarrhea and elevations in liver enzymes, A week later a second patient showed up — a farmer in his 80s who’d been picking and eating mushrooms all his life. “This time he happened to pick the wrong ones,” Tran Hawkins said.

Within another week, two more patients came to their center with similar symptoms and elevated liver enzymes.

Clinicians there immediately suspected poisoning by mushrooms of the genus Amanita, which is cited in more than 90% of fatal mushroom poisoning cases, Tran Hawkins said. One species, Amanita phalloides, is known as the “death cap” because it’s so lethal.

According to data from the National Poison Data System, there were are about 5,912 cases of mushroom poisoning in 2010, with 478 moderate and 23 major outcomes, and one death. Some estimates, however, have put the mortality rate higher, researchers said.

Common treatments include charcoal or penicillin G, but when the MGUH team contacted the local Poison Control Center, they were put in touch with a California physician who’d been investigating another agent for treatment of mushroom toxicity: intravenous silibinin, an extract of milk thistle seeds that competes with amatoxin binding in hepatocytes, preventing uptake in the liver.

Although it’s investigational in the U.S., silibinin is approved in Europe as Legalon, and has been shown to work in animal models. Tran Hawkins said it’s also been known “since Biblical times to treat liver and biliary disease.”

Todd Mitchell, MD, MPH, of Dominican Santa Cruz Hospital, is leading the first U.S. trial of silibinin for mushroom poisoning, which is funded by Madaus, the German company that markets Legalon in Europe.

Mitchell said he’s had about 40 cases nationwide since the trial started in February 2010, including the four MGUH patients, and now has two locations from which to ship the drug — one at his hospital and another in Pittsburgh.

That way, patients on either coast can get started within 24 hours of ingestion — sufficient time, he said, as he’s given it successfully to patients within 96 hours of exposure. That was in a family of six who’d suffered Amanita poisoning, Mitchell’s first encounter with the toxin — “my baptism, as it were, into the world of amatoxin poisoning.”

While researching the condition during that first incident, he learned the drug was available in Europe, and was able to obtain an emergency Investigational New Drug (IND) permit from the FDA to give the drug to the six patients. All made a recovery, except the 82-year-old grandmother, a diabetic, who died.

For the first case at MGUH, Mitchell was able to send the team there an emergency shipment of intravenous silibinin, also permitted under an emergency use exemption.

MGUH was still in the process of establishing an actual trial protocol at their facility, given the likelihood that more patients would be showing up with mushroom toxicity, when the second patient presented in the emergency department.

An emergency meeting of the center’s Institutional Review Board approved the protocol so the patient could receive the investigational agent, Tran Hawkins said.

“Everyone got together so quickly to get things done for these patients,” she said. “A lot of patients … don’t do well and end up either in liver transplant or death. We were very fortunate.”

In addition to the silibinin, two of the patients also had a nasobiliary drain, which also helps remove the toxin before it can damage the hepatocytes, Tran Hawkins said, and is typically reserved for the more severe cases.

All of the patients were released within 4 to 7 days of their arrival in the hospital, she said, with their liver function restored.

Mitchell acknowledges that survival rates from mushroom poisoning in the U.S. are better now than in the past, and that patients can recover “with good supportive care alone.”

Also, the first concern in these patients tends to be improving kidney function by reversing the severe dehydration associated with poisoning, he said.

Still, the liver can be severely damaged, especially in patients with a large ingestion, which isn’t uncommon given that just one “death cap” mushroom can kill a patient, he said.

Robert Glatter, MD, an emergency physician at Lenox Hill Hospital in New York, said when he’s encountered mushroom toxicity, he’s relied on staple treatments such as charcoal, penicillin G, and acetylcysteine (Mucomyst), but that intravenous silibinin “is certainly worthwhile to try.”

More importantly, he said, is that clinicians recognize the problem in the first place, especially given its long latency period and a presentation that mimics gastroenteritis.

Also, urban centers where mushroom toxicity wouldn’t normally be suspected should be extra vigilant in summer and fall, when mushrooms most often sprout, he said.

“Taking a dietary history and asking about mushrooms is key,” Glatter said. “It looks like gastroenteritis until they tell you they were at a picnic and ate mushrooms.”

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Kristina Fiore

Staff Writer

Kristina Fiore joined MedPage Today after earning a degree in science, health, and environmental reporting from NYU. She’s had bylines in newspapers and trade and consumer magazines including Newsday, ABC News, New Jersey Monthly, and Earth Magazine. At MedPage Today, she reports with a focus on diabetes, nutrition, and addiction medicine.

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