October 23, 2020

Treating Amanita (Mushroom) Toxicity in Children

Silibinin for amatoxin poisoning

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With changes in global weather patterns, toxic mushrooms (Amanita phalloides, also known as Death Caps) seem to be sprouting more often in North America, including northern Ohio. People are accidentally consuming them, having mistaken them for edible fungus. Amanita is the most common cause of fatal mushroom poisoning and impacts the body through amatoxin, which binds to RNA polymerase II and causes inhibition of protein synthesis. Amanita can also cause hepatocyte apoptosis. Ingestion leads to gastrointestinal symptoms like abdominal cramps, vomiting and severe diarrhea, and acute liver failure and may necessitate liver transplantation. Symptoms generally appear six to eight hours after ingestion.

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Silibinin with other supportive therapies

Silibinin is a milk thistle extract that has proven antioxidative and anti-inflammatory properties and has been shown to block cellular amatoxin re-uptake and stop hepatocyte apoptosis. It is an antidote for amanita toxicity that is undergoing the FDA approval process and was given orphan drug designation for treatment of amatoxin poisoning.

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The pediatric hepatology and transplant team at Cleveland Clinic Children’s has accrued good experience over the years, managing patients with amanita toxicity medically with silibinin (Legalon SIL) along with other supportive therapies, as part of a medical trial. This was an open-label treatment trial designed to provide Legalon SIL as early as possible to patients with amatoxin poisoning. Experience in Europe and the U.S. suggests that this medication reduces mortality and the need for liver transplant by more than 50 percent in acute liver failure, if used at the appropriate time. The study was run by Cleveland Clinic pediatric hepatologists, Kadakkal Radhakrishnan, MD, and Vera
Hupertz, MD, in conjunction with the adult intensive care team, and is now closed. The treatment remains available, if needed, as the company has arranged for Emergency Investigational New Drug status.

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