Amatoxins are rapidly absorbed from the intestine and transported into the liver by OATP transporters. Once in the hepatocyte they start to inhibit RNA polymerase. It takes about 24 hours before any signs or laboratory indicators of liver injury begin to appear.

The course of Amanita toxicity has three phases:

1. The first stage does not begin until six to 12 hours after ingestion; often foragers comment on how good the food made from Amanita species tastes, and there are no signs of a problem for at least 6 hours. After this silent phase, it is followed by the onset of nausea, abdominal cramps, profuse watery diarrhea, and signs of dehydration. A physical exam may reveal dry mucosal membranes and tachycardia, and given sufficient dehydration, hypotension.
2. After the GI phase, the second stage appears where the patient appears to recover transiently, and GI symptoms resolve, but ongoing liver damage continues. This stage may last two to three days and is characterized by rising liver function transaminase, bilirubin, the development of coagulopathy, and eventually hepatic encephalopathy.
3. In the third stage, both liver and renal function become compromised. Hepato-renal syndrome and hepatic encephalopathy may occur rapidly after laboratory signs of liver injury, and death can occur in three to seven days.

All ingestions of suspected liver-toxic mushrooms should have a complete chemistry panel to include liver function tests and a baseline INR.[5]

The treatment of Amatoxin mushroom toxicity is predominately supportive care. There is no specific antidote. The patient must have two large bore IVs and fluid loss, electrolyte deficiency, and glucose should be normalized. If the patient presents early (within two to four hours,) decontamination with oral activated charcoal may be performed. Once the stomach is empty, nausea should be treated if needed.[1][2]

Several agents have been used and have anecdotal support in the literature:

1. N-acetyl-cysteine: Used intravenously (IV) as per acetaminophen poisoning to treat potential liver injury, and provide glutathione.
2. Penicillin: High dose IV  (four million units every four hours) is thought to compete with the liver uptake of the amatoxin.
3. Silymarin: Both the pharmaceutical form available in Europe as an intravenous formulation and the over the counter raw milk thistle extract used in North America have been used in a majority of cases in the literature. Its mechanism of action is felt to be an OAT-P transporter inhibitor that slows the entry of amatoxin into the liver. Doses are 1 gm orally four times daily, or its purified alkaloid silibinin intravenously  5 mg/kg IV over one hour, followed by 20 mg/kg/day as a constant infusion.
4. Activated charcoal: May reduce absorption of amatoxins if given early after ingestion and may also prevent toxin readsorption hours later as amatoxins undergo enterohepatic recirculation. A dose of 1 g/kg may be given every 2 to 4 hours.
5. A variety of other therapies, such as intravenous cimetidine or thioctic acid, have been tried but have only animal model support.

In selected cases, once a severe liver injury occurs, despite aggressive fluid resuscitation and supportive care, a liver transplant may be the only life-saving option. Rapid progression to hepatic encephalopathy, hepatorenal syndrome, or coagulopathy are indications for liver transplantation. Consideration to transfer to a liver transplant setting and intensive care unit care should be done early in the course of mushroom ingestions.

When renal failure occurs, dialysis should be used, but its use even early after an ingestion does not remove Amatoxin from the blood.

Confirmatory testing of amatoxin exposure is rarely available and relies on a strong supporting history. Thus, appropriate consideration should be given to other causes of acute hepatitis and liver failure such as acetaminophen overdose, infection, and autoimmune disorders.

• Renal and liver toxicity
• Encephalopathy
• Dehydration
• Pancreatitis
• Neuropathy

A regional poison control center or medical toxicologist should be consulted in cases of amatoxin-containing mushroom exposure or suspected amatoxin hepatotoxicity. Additionally, poison control centers often collaborate with local mycologists who may be able to aid in mushroom identification.

The prognosis is dependent on the mushrooms ingested and the amount of time it takes to seek care.

Death is rare if treatment is started immediately, and although fatalities continue to be reported, they occur in less than 5% of all cases in developed countries with early access to intensive care.

The diagnosis of amatoxin poisoning can be made by the classic clinical course of rising liver transaminases within two to three days of foraging for mushrooms.

Certain specialty laboratories can measure serum concentrations of amatoxin in blood, but the test is not reliable and often negative once symptoms begin.

Mushroom poisoning is not very common in the US but the toxicity can be very serious. Because the toxin can affect many organs in the body, an interprofessional team approach is necessary to make the diagnosis and manage the poisoning. The key factor that determines the outcome is the amount consumed. Data also indicate that there are some individual variations in absorption; children tend to absorb higher doses of the toxin compared to adults and consequently have a much higher morbidity and mortality. The mortality rates following mushroom poisoning have dropped significantly in the US but liver failure appears to be a common adverse complication. There are reported cases where individuals have required an immediate liver transplant as a lifesaving measure. The key to preventing mushroom poisoning is education of the public. In some cases, the mushrooms are safe but have been sprayed with toxic pesticides, hence thorough washing of the food is essential. There is no single test that can determine which mushroom is toxic; the best advice is do not eat wild mushrooms but instead buy them from a grocery store.[6][7][6] (Level V)