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Amatoxin Toxicity

  • Author: Douglas S Lee, MD; Chief Editor: Timothy E Corden, MD  more...
 
Updated: Jul 21, 2015
 

Background

The Greek playwright Euripides recorded the first documented deaths due to mushroom poisoning, or mycetismus, upon describing a family’s fatal mushroom ingestion. Today, most reports of deadly mushroom ingestion come from central and Eastern Europe.

Almost 50 of the more than 5000 species of mushrooms are poisonous to humans. The Amanita species are reputed to be responsible for 90% of fatal mushroom poisonings worldwide; however, Amanita poisonings are uncommon in North America (see Epidemiology).

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. At least 5 subtypes of amatoxins exist; 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 Center and the Poisoning - First Aid and Emergency Center, as well as Poisoning and Activated Charcoal.

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Pathophysiology

Amatoxins are found in several 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). A 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. The lethal dose is less than 0.1 mg/kg. 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. First, there is a characteristic latent period of 6-12 hours post ingestion before the onset of clinical symptoms. 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.

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Etiology

Amatoxin toxicity is caused by the ingestion of mushrooms containing the toxin (especially A phalloides), such as may occur in any of the following circumstances:

  • Amateur mushroom hunters seeking a fresh-picked meal
  • Adults and adolescents seeking psychotropic mushrooms (eg, Amanita muscaria)
  • 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).


					Amanita phalloides.
				Amanita phalloides.

					Amanita muscaria.
				Amanita muscaria.

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.

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Epidemiology

United States statistics

In 2013, a total of 6,204 single exposures to toxic mushrooms were reported to the National Poison Data System of the American Association of Poison Control Centers (AAPCC). In 5342 of those exposures, the mushroom type was unknown. Mushrooms containing cyclopeptides accounted for 27 exposures.[1, 2, 3]

International statistics

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 mid-July and September of 1998, 9 people died and 180 were poisoned from mushrooms in Russia. In July and August of 1997, 34 people died of mushroom poisoning across Russia. 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.[4]

Age-related demographics

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.

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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. In the 2013 AAPCC National Poison Data System annual report, one death due to mushroom exposure were reported, from a mushroom of an unknown type. None of the 27 cyclopeptide mushroom exposures proved fatal.[1] Ninety-five percent of all mushroom fatalities in North America are associated with cyclopeptide-containing species (amatoxins).

Worldwide, most mushroom fatalities are ascribed to amatoxins. Most mortality statistics for amatoxin poisoning are from Europe, where the number of victims is larger.[5] Figures of 10-60% have been reported. With current therapies, mortality from A phalloides poisoning is 20-30%. One case series reported a mortality of 51% in patients younger than 10 years; this higher rate may be due to the lower body weight of children.

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.[6] 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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Contributor Information and Disclosures
Author

Douglas S Lee, MD Attending Physician, Department of Emergency Medicine, Naples Community Hospital

Douglas S Lee, MD is a member of the following medical societies: American Academy of Emergency Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Theodore Bania, MD Program Director, Assistant Director of Research, Assistant Professor, Department of Emergency Medicine, Division of Toxicology, St Luke's-Roosevelt Hospital Center, Columbia University

Theodore Bania, MD is a member of the following medical societies: American College of Emergency Physicians, American Medical Association, New Mexico Medical Society, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Matthew R Denny, MD, MPH Staff Physician, Department of Emergency Medicine, Santa Clara Valley Medical CenterClinical Instructor, Department of Emergency Medicine, Stanford University School of Medicine

Matthew R Denny, MD, MPH is a member of the following medical societies: American College of Emergency Physicians

Disclosure: Nothing to disclose.

Suzanne Bentley, MD Assistant Professor, Departments of Emergency Medicine and Medical Education, Elmhurst Hospital, Mount Sinai School of Medicine

Suzanne Bentley, MD is a member of the following medical societies: American College of Emergency Physicians, American Medical Association, American Medical Womens Association, Society for Academic Emergency Medicine, Emergency Medicine Residents' Association

Disclosure: Nothing to disclose.

Chief Editor

Timothy E Corden, MD Associate Professor of Pediatrics, Co-Director, Policy Core, Injury Research Center, Medical College of Wisconsin; Associate Director, PICU, Children's Hospital of Wisconsin

Timothy E Corden, MD is a member of the following medical societies: American Academy of Pediatrics, Phi Beta Kappa, Society of Critical Care Medicine, Wisconsin Medical Society

Disclosure: Nothing to disclose.

Acknowledgements

Jeffrey Glenn Bowman, MD, MS Consulting Staff, Highfield MRI, Columbus, Ohio

Disclosure: Nothing to disclose.

Andrew K Chang, MD Associate Professor, Department of Emergency Medicine, Albert Einstein College of Medicine, Montefiore Medical Center

Andrew K Chang, MD is a member of the following medical societies: American Academy of Emergency Medicine, American Academy of Neurology, American College of Emergency Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Michael Hodgman, MD Assistant Clinical Professor of Medicine, Department of Emergency Medicine, Bassett Healthcare

Michael Hodgman, MD is a member of the following medical societies: American College of Medical Toxicology, American College of Physicians, Medical Society of the State of New York, and Wilderness Medical Society

Disclosure: Nothing to disclose.

Michael E Mullins, MD Assistant Professor, Division of Emergency Medicine, Washington University in St Louis School of Medicine; Attending Physician, Emergency Department, Barnes-Jewish Hospital

Michael E Mullins, MD is a member of the following medical societies: American Academy of Clinical Toxicology and American College of Emergency Physicians

Disclosure: Johnson & Johnson stock ownership None; Savient Pharmaceuticals stock ownership None

Asim Tarabar, MD Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital

Disclosure: Nothing to disclose.

Jeffrey R Tucker, MD Assistant Professor, Department of Pediatrics, Division of Emergency Medicine, University of Connecticut School of Medicine, Connecticut Children's Medical Center

Disclosure: Merck Salary Employment

John T VanDeVoort, PharmD Regional Director of Pharmacy, Sacred Heart & St. Joseph's Hospitals

John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

References
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Amanita muscaria.
Amanita phalloides.
 
 
 
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