Practice Essentials
Amatoxin toxicity is caused by the ingestion of mushrooms containing these cyclopepeptide toxins, especially Amanita phalloides (see the image below), commonly known as the death cap. Amatoxins are also found in several other Amanita species (phalloides, bisporigera, hygroscopia, ocreata, suballiacea, tenuifolia, verna, and virosa), as well as in some species of the genera Galerina (autumnalis, marginata, and venenata) and Lepiota (brunneoincarnata, chlorophyllum, helveola, and josserandii).
Amanita species are reputed to be responsible for 90% of fatal mushroom poisonings worldwide. Most reports of deadly mushroom ingestion come from central and eastern Europe; Amanita poisonings are uncommon in North America (see Epidemiology). [1]
Most fatalities resulting from mushroom ingestion are associated with amatoxins within the mushrooms (see Pathophysiology). Amatoxins (cyclic octapeptides) represent 1 of the 3 major groups of cyclopeptides (in addition to phallotoxins and virotoxins). They are heat-stable, insoluble in water, and not destroyed by drying. Although virotoxins are cyclopeptides, they have not been described to cause toxicity in humans. There are at least 5 subtypes of amatoxins; the most significant of these are the alpha and beta subtypes of amanitin.
Amatoxin toxicity occurs over several days and usually develops in 3 characteristic stages, with the examination approach and findings depending on the stage of the poisoning (see Presentation). The workup may include laboratory studies, diagnostic imaging (though specific studies are not indicated if there is already a clear history of mushroom ingestion), and analysis of mushroom specimens if available (see Workup).
Treatment approaches include aggressive intravenous (IV) fluid and electrolyte therapy, gastric decontamination, pharmacologic therapy, and, in selected cases, liver transplantation (see Treatment).
It is important to provide education regarding the dangers of amateur mushroom hunting. For patient education resources, see the Poisoning - First Aid and Injuries Center.
Pathophysiology
Amanita phalloides, commonly known as death cap, is generally considered the most toxic of the world’s cyclopeptide-containing mushrooms. The clinical manifestations of an A phalloides ingestion are caused by the cyclopeptide phallotoxins and amatoxins. Phalloidin, a cyclic heptapeptide, causes gastroenteritislike effects 6-12 hours after initial ingestion. It interrupts the actin polymerization-depolymerization cycle and impairs cell membrane function. Phalloidin has limited gastrointestinal (GI) absorption, and symptoms improve within hours of supportive care.
The cyclic octapeptide amanitins, primarily alpha-amanitin, are responsible for the hepatic, renal, and encephalopathic effects. Amatoxins inhibit RNA polymerase II, thereby interfering with DNA and RNA transcription. These toxins mainly affect tissues with high rates of protein synthesis, including the liver, kidneys, brain, pancreas, and testes.
About 60% of absorbed alpha-amanitin is excreted into the bile. The liver is exposed to high concentrations of toxin through the portal system and via the enterohepatic circulation. Hepatocytes are damaged early, with sparing of the hepatic sinusoids. In these cases, fatty degeneration of the hepatic parenchyma and patterns of centrilobular necrosis with hemorrhage are typical.
Amatoxin is eliminated in the urine, gastroduodenal fluids, and feces for several days after ingestion. A single gram of fresh A phalloides can yield approximately 0.2-0.4 mg of alpha-amanitin [2] . The lethal dose is estimated to be approximately 0.1 mg/kg but there are cases of survival with larger ingestions [3] . The toxins of A phalloides are stable to cooking and remain active in dried mushrooms.
The clinical course of amatoxin poisoning can be divided into 3 stages. The first stage is preceded by a characteristic latent period that lasts for 6-12 hours following ingestion. After this asymptomatic period, abdominal cramping, vomiting, and profuse watery diarrhea (rice-water or choleralike) occur. Fluid losses may be severe enough to cause profound dehydration and even circulatory collapse.
Once this acute GI phase is over (usually after about 24 hours), the second stage begins. Although the patient appears to have improved clinically, ongoing liver damage is occurring, as indicated by laboratory abnormalities (eg, elevation of serum aminotransferase levels and lengthening of the prothrombin time [PT]). This stage may last as long as 2-3 days.
In the third and final phase, hepatic and renal injury become clinically apparent and may progress to fulminant hepatic failure (FHF). Death may occur in 3-7 days.
Etiology
Amatoxin toxicity is caused by the ingestion of mushrooms containing the toxin (especially Amanita phalloides), such as may occur in any of the following circumstances:
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Amateur mushroom hunters seeking a fresh-picked meal
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Adults and adolescents seeking psychotropic mushrooms (eg, Amanita muscaria)
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Unsupervised children in suburban or rural areas
Even experts can mistake A phalloides, also known as the death cap, for similar-looking nontoxic mushrooms (see the images below).
A phalloides has no characteristic odor or offensive taste. It is large, with a hemispherical cap 5-15 cm in diameter located on a central stem that is 8-15 cm long and 1-2 cm in diameter. The weight of an average intact mushroom is approximately 25 g. The cap is usually dry and shiny, with a light green-yellow color darkening towards the center. Gills are located under the cap and are not attached to the stem. Incomplete excavation of the entire mushroom may leave behind the volva, or cup, at the base of the stem.
In the United States, Amanita species are most commonly found in the Pacific Northwest and the Blue Ridge Mountains of the Northeast, but they are increasingly being identified in Pennsylvania, New Jersey, and Ohio. They tend to grow near filbert (hazelnut), chestnut, or oak trees. The peak season extends from late summer into fall; however, mushrooms can also be found in early winter.
Epidemiology
In 2021, a total of 6458 single exposures to toxic mushrooms were reported to the National Poison Data System of the American Association of Poison Control Centers (AAPCC). In 4887 of those exposures, the mushroom type was unknown. Mushrooms containing cyclopeptides accounted for 86 exposures, with 6 major outcomes and one death. [4]
Over the course of 2 weeks in December 2016, California Poison Control System (CPCS) investigated 14 suspected A phalloides ingestions in five northern California counties. One of those patients, a child, developed cerebral edema and suffered permanent neurologic sequelae. All the remaining patients recovered completely, although 3 patients received liver transplants because of irreversible fulminant hepatic failure. [5]
At present, there is no adequate database on which accurate estimates of worldwide exposures can be based. Mushroom foraging is known to be more common in parts of Europe and Russia than in other parts of the world. Between January 1995 and December 2009, 5638 inquiries concerning human exposures to mushrooms were reported to the Swiss Toxicological Information Centre, accounting for 1.2% of all inquiries. Death occurred in five of the 32 confirmed amatoxin poisonings. [6] A review of mushroom toxicity globally found mortality rates were highest in China, Russia and the Ukraine. [7]
Of 67 cases of mushroom poisoning reported in Hong Kong between July 2005 and June 2015, 7 were confirmed amatoxin poisoning by consumption of A farinosa resulting in one death and 2 liver transplantations. This is the first report of this Amanita species in Hong Kong. [8]
Mycetismus commonly is due to amateur mushroom picking or accidental ingestions by unsupervised children. Most unintentional mushroom exposures occur in children younger than 6 years. Mortality is higher in children because they absorb a larger dose of toxins per kilogram of body weight.
Prognosis
The primary factor determining the prognosis is the quantity of mushroom that was eaten. In some cases, ingestion of a single A phalloides mushroom can be lethal. However, variations in individual susceptibility to amatoxin have been reported, and as noted, children absorb proportionally higher doses of toxins than adults do and are more likely to die of the poisoning.
With good supportive care, mortality from amatoxin toxicity is now lower than it once was. Worldwide, most mushroom fatalities are ascribed to amatoxins. Most mortality statistics for amatoxin poisoning are from Europe, where the number of victims is larger. [6] Figures of 10-60% have been reported. With current therapies, mortality from A phalloides poisoning is 10-20%. [9]
Liver failure is the most serious complication of amatoxin ingestion. It may be complicated by hepatic coma and hypoglycemia. Various studies have shown that some who recover from acute liver failure may go on to develop chronic liver disease. The mechanism of development of related chronic liver disease is unknown, but it is thought that changes in hepatocyte structure may induce autoimmunity, leading to chronic hepatitis with potential progression to end-stage liver disease. [10]
Liver transplantation can save the life of a patient with the most severe amatoxin poisoning. A retrospective study concluded that the prothrombin index in combination with the serum creatinine level from day 3 to day 10 after ingestion may help predict those patients needing liver transplantation. [11] In this study, an international normalized ratio (INR) of 2.5 or higher along with a serum creatinine level greater than 106 µmol/L was predictive of a fatal outcome.
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Amanita muscaria.
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Amanita phalloides.
