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AUTHOR AND EDITOR INFORMATION
Section 1 of 10  
Author: Douglas S Lee, MD, Attending Physician, Department of Emergency Medicine, Naples Community Hospital
Douglas S Lee is a member of the following medical societies: American Academy of Emergency Medicine
Coauthor(s):
Theodore Bania, MD, Program Director, Assistant Director of Research, Department of Emergency Medicine, Division of Toxicology, Assistant Professor, St Luke's-Roosevelt Hospital Center, Columbia University;
Matthew R Denny, MD, MPH, Staff Physician, Department of Emergency Medicine, Mt Sinai Hospital
Editors: Michael E Mullins, MD, Assistant Professor, Department of Emergency Medicine, Washington University School of Medicine; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Jeffrey R Tucker, MD, Assistant Professor, Department of Pediatrics, Division of Emergency Medicine, University of Connecticut and Connecticut Children's Medical Center; Paul D Petry, DO, FACOP, FAAP, Consulting Staff, Freeman Pediatric Care, Freeman Health System; Maureen Strafford, MD, Arnold P Gold Foundation Associate Professor, Departments of Anesthesiology and Pediatrics, Tufts University and Tufts-New England Medical Center
Author and Editor Disclosure
Synonyms and related keywords:
amatoxin, death angel, death cap, mushroom poisoning, Amanita, Amanita species, Amanita poisoning, Amanita phalloides, A phalloides, amanitin, alpha-amanitin
Background
The Greek poet Euripedes 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 2000 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 and were responsible for 2 of 6 deaths caused by mushroom poisoning in a 5-year period in the United States.
Even experts can mistake Amanita phalloides, also known as the death cap, for similar-looking nontoxic mushrooms. The mushroom has no characteristic odor. It is large with a hemispherical cap 5-15 cm in diameter located on a central stem 8-15 cm long and 1-2 cm in diameter. The weight of an average intact mushroom is approximately 25 g. The cap usually is dry and shiny with a light green-yellow color darkening towards the center. Gills are located under the cap, and they 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 most commonly are found in the Pacific Northwest and the Blue Ridge Mountains of the Northeast. They tend to grow near filbert (hazelnut), chestnut, or oak trees. Peak season is late summer into fall; however, mushrooms can be found in early winter.
Pathophysiology
The clinical manifestations of an A phalloides ingestion are the result of the cyclopeptide toxins, phalloidin and amatoxin. Phalloidin causes gastroenteritislike effects 6-12 hours after initial ingestion. Phalloidin, a cyclic heptapeptide, interrupts the actin polymerization-depolymerization cycle and impairs cell membrane function. Phalloidin has limited gastrointestinal absorption, and symptoms improve within hours of supportive care.
Amanitins, primarily alpha-amanitin, are responsible for the hepatic, renal, and encephalopathic effects. Amatoxin, an octapeptide, inhibits ribonucleic acid (RNA) polymerase II, therefore interfering with DNA and RNA transcription. The toxin mainly affects 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.
Frequency
United States
The 1998 American Association of Poison Control Centers (AAPCC) annual report lists 9839 mushroom exposures, of which 40 were known to be from cyclopeptides-containing mushrooms. This is likely an underestimation because of the difficulty in identifying the offending agent. Children make up approximately one half of the potential cyclopeptide exposures in the United States.
Mortality/Morbidity
- In 1998, no deaths in the United States were attributed to cyclopeptides. Most mortality statistics are from Europe, where the number of victims is larger. With current therapies, mortality from A phalloides is 20-30%.
- In general, the mortality rate is higher in children than adults. One case series reports mortality of 51% in patients younger than 10 years. This may be due to the lower body weight of children.
Age
Mycetismus commonly is due to amateur mushroom picking or accidental ingestions by unsupervised children.
History
- Collect important information about the ingestion of wild mushrooms, which generally occurs at least 6 hours before the onset of symptoms.
- Time of ingestion
- Time of onset of symptoms
- Phalloidin causes gastrointestinal symptoms about 6-12 hours after ingestion.
- Renal and liver toxicity caused by amanitin is evident 24-48 hours after ingestion.
- Description of mushrooms
- Location at which mushrooms were obtained
- Other mushrooms and co-ingestants: Gastrointestinal symptoms may occur earlier than 6 hours due to other mushrooms ingested at the same time; however symptoms from isolated A phalloides usually begins at least 6-12 hours after the ingestion.
- Make efforts to identify other toxins ingested during an attempted suicide.
- Toxicity from A phalloides occurs over several days and usually is divided into stages.
- Stage I: Sudden onset of nausea, vomiting, watery diarrhea, and cramping abdominal pain occurs 6-12 hours after ingestion. Patients may become dehydrated and hypotensive during this episode. Patients often present during this stage, and, if misdiagnosed, may be discharged erroneously without further care.
- Stage II: Clinical improvement occurs with supportive care. Despite the resolution of symptoms, hepatic and renal damage is ongoing, which is evident by rising laboratory test values.
- Stage III: If discharged, patients may return to the hospital 2-6 days later with severe coagulopathy, renal failure, and encephalopathy.
Physical
- The examination depends upon the stage of the poisoning.
- Vital signs
- Due to profuse vomiting and watery diarrhea, the patient may present in hypovolemic shock during the gastrointestinal phase.
- Tachycardia
- Hypotension
- Head, ears, eyes, nose, and throat: Epistaxis or scleral icterus that is related to hepatic failure may appear in a patient with delayed presentation.
- Abdominal: The patient can have mild diffuse tenderness, and a rectal examination will reveal occult bloody stool. Hepatomegaly results from hepatitis late in the course of the disease.
- Neurologic: Effects are related to hepatic failure. Depending on the time that elapses after ingestion, the examination findings may vary from normal to agitation, somnolence, seizures, or coma.
Causes
- Causes include ingestion by any of the following:
- Amateur mushroom hunters seeking a fresh picked meal
- Adults and adolescents seeking psychotropic mushrooms
- Unsupervised children in suburban or rural areas
Appendicitis
Cholera
Dehydration
Food Poisoning
Gastroenteritis
Hepatitis A
Hepatitis B
Hepatitis C
Toxicity, Acetaminophen
Toxicity, Iron
Other Problems to be Considered
Other cyclopeptide-containing mushrooms Amanita verna
Amanita virosa
Galerina autumnalis
Galerina maginata
Galernia venenata
Lepiota brunneoincarnata
Lepiota chlorophyllum
Lepiota helveola
Lab Studies
- Electrolytes, glucose, BUN, and creatinine
- Abnormalities may be due to vomiting, diarrhea, and dehydration.
- Progression to renal failure causes a further rise in BUN and creatinine.
- Liver function tests may be normal on presentation; however, elevation may occur after 24-48 hours.
- Aspartate transaminase
- Alanine transaminase
- Lactic acid dehydrogenase
- Bilirubin
- Prothrombin time (PT) and/or activated partial thromboplastin time (aPTT)
- Severe coagulopathy may develop as the toxicity progresses to later stages.
- PT is considered a reliable prognostic indicator for Amanita poisoning.
- Urinalysis
- Microscopic hematuria may occur in stage I.
- Oliguria and anuria develop with renal failure.
- Amylase and lipase: A phalloides can directly induce pancreatitis.
Imaging Studies
- Specific studies are not indicated with the history of Amatoxin ingestion.
- If the history is unknown, abdominal film may be obtained to rule out obstruction.
- Ultrasound and CT scan are performed to narrow the differential but will not have positive findings.
Other Tests
- Meixner test
- This test can detect amatoxin concentrations as low as 0.2 mg/mL.
- Place uneaten mushrooms in a dry paper bag for transport.
- If the patient can provide a sample of the mushrooms that were ingested, a drop of liquid from a fresh mushroom can be expressed onto a lignin-containing paper (eg, print-free newspaper). After the paper has dried, a drop of concentrated hydrochloride (HCl, 10-12 N) is added. If amatoxins are present, a blue color will develop within 2 minutes.
- A dried mushroom may be tested by crushing it in pure methanol and using a drop of the methanol before adding the HCl. This test is not valid on stomach contents.
- Determining if a test result is positive can be difficult, and the clinical use of the Meixner test is questionable.
- Spore analysis in stomach contents
- Spores can be examined by light microscopy using an oil immersion lens after isolation and concentration via centrifuge.
- The spores are examined in both water and Melzer solution.
- The spores of amatoxin-containing Amanita mushrooms are smooth and turn blue in Melzer solution.
- Whether the spores of Amanita species survive the digestive process and pass into the stool is unknown.
- Radioimmunoassay, thin-layer chromatography, and high-performance liquid chromatography
- These tests can measure the toxin in the serum, though these methods generally are not available.
- Amatoxins are eliminated very rapidly from the serum. Levels have no prognostic significance.
Histologic Findings
Excised livers from patients with Amanita poisoning reveal massive hepatic centrilobular necrosis with resultant hemorrhage. If allowed to progress, the poisoning causes lobular collapse and regenerative changes.
Medical Care
- Early management of airway, breathing, and circulation (ABCs) and IV access is important. Supportive care with IV hydration and correction of electrolyte abnormalities lead to symptomatic improvement.
- If the patient presents less than 1 hour after known ingestion of cyclopeptide-containing mushrooms, consider gastric decontamination via gastric lavage or vomiting. Patients who present with nausea and vomiting within 1-2 hours of ingestion of a mushroom most likely have consumed a less toxic mushroom. Administer activated charcoal in patients who are asymptomatic with suspected Amanita ingestion. Patients who are asymptomatic with ingestions of unknown or unidentified mushrooms may receive activated charcoal and observation for 6-12 hours. Most patients with confirmed Amanita poisoning arrive later than 6 hours after ingestion and usually are vomiting on presentation, which may obviate the need for ipecac or lavage.
- Activated charcoal (1 g/kg) is recommended once vomiting ceases. Multidose activated charcoal or whole bowel irrigation (WBI) may be helpful in disrupting the enterohepatic circulation.
- Hemodialysis and hemoperfusion have been proposed as methods to remove circulating amatoxin from the blood. Clear recommendations cannot be made, but hemodialysis may be necessary in those patients who develop renal failure.
- The Molecular Adsorbent Recirculation System (MARS), a form of hepatic albumin dialysis, may have a role in bridging critically ill patients to liver transplantation or to spontaneous recovery of liver function.
Surgical Care
- Precise indications for liver transplantation are controversial. Some patients will recover liver function with medical therapy alone and some will not. Efforts have been made to identify early on which patients will require transplantation, thus expediting donor location and avoiding unnecessary transplants. Proposed criteria have included graded hepatic encephalopathy, prothrombin time, and creatinine level. Consider orthotopic liver transplantation in patients who develop any of the following:
- Two-fold prolongation in PT, despite fresh-frozen plasma
- Persistent hypoglycemia
- Serum bilirubin levels greater than 25 mg/dL
- Azotemia
- Grade III or grade IV hepatic encephalopathy
Consultations
- Regional poison control center
- Expert mycologist or local mycological society
- Transplant center
Given the delay between ingestion and the development of clinical symptoms, the role of gastric decontamination may be more limited than with other intoxications. However, multidose activated charcoal may still have a role in interrupting enterohepatic circulation of amatoxin. Clear benefit has not been established.
No FDA-approved specific antidote for cyclopeptide poisoning exists. Intravenous silymarin (derived from the Mediterranean milk thistle plant) is the treatment of choice in Europe, but the antidote is not available in the United States. It appears to act by preventing passage of amatoxin across the hepatocyte cell membrane. Other therapies that have been suggested are benzylpenicillin (penicillin G), N-acetylcysteine, thioctic acid, cimetidine, cytochrome C, and hyperbaric oxygen. Given the rarity of toxic mushroom ingestion and the difficulties in designing prospective trials, evidence is limited to animal studies and retrospective analysis in humans. Because these suggested therapies are unapproved, consult with a medical toxicologist from the nearest regional poison control center before undertaking a course of therapy.
Drug Category: Gastrointestinal decontaminations
Activated charcoal may reduce the amount of toxin absorbed.
| Drug Name | Activated charcoal (Liqui-Char) |
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| Description | Used for emergency treatment in poisoning caused by drugs and chemicals. Network of pores present in activated charcoal adsorbs 100-1000 mg of drug per gram of charcoal. Does not dissolve in water.
For maximum effect, administer within 30 min of ingesting poison. |
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| Adult Dose | 1 g/kg (25-100 g) PO or via NG tube q4h for 48 h |
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| Pediatric Dose | Infants: 1 g/kg PO or via NG tube q4h for 48 h
Children: 25-50 g PO or via NG tube q4h for 48 h |
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| Contraindications | Documented hypersensitivity; poisoning or overdosage of mineral acids and alkalies; absent bowel sounds or inability to protect airway |
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| Interactions | May inactivate ipecac syrup if used concomitantly; effectiveness of other medications decreases with coadministration; do not mix with sherbet, milk, or ice cream (decreases adsorptive properties) |
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| Pregnancy | C - Safety for use during pregnancy has not been established.
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| Precautions | Administering cathartic is not necessary; not effective in poisonings of ethanol, methanol, or iron salts; induce emesis before administering; after emesis with ipecac syrup, patient may not tolerate activated charcoal for 1-2 h; can administer in early stages of gastric lavage; without sorbitol, gastric lavage returns are black in color |
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Drug Category: Potentially beneficial medications
The literature is fraught with case studies and trials. Decreases in mortality are likely due to improved supportive care.
| Drug Name | Penicillin G (Pfizerpen) |
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| Description | May displace amanitin from plasma proteins, thus increasing the renal excretion. May inhibit amanitin from entering hepatocytes. May bind to acid amanitin. |
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| Adult Dose | 300,000-1,000,000 U/kg/d IV infusion |
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| Pediatric Dose | Infants: 600,000 U/d IV in divided doses
Children: 900,000-1,200,000 U/d IV in divided doses |
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| Contraindications | Documented hypersensitivity |
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| Interactions | Probenecid can increase effects of penicillin; coadministration of tetracyclines can decrease effects of penicillin |
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| Pregnancy | B - Usually safe but benefits must outweigh the risks.
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| Precautions | Possible cross sensitivity to cephalosporin antibiotics; caution in impaired renal function |
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| Drug Name | Silibinin (Legalon) |
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| Description | A flavolignone isolated from the milk thistle Silybum marianum. Also known as silymarin or silidianin. May interrupt the enterohepatic circulation of the toxin or inhibit the penetration of amanitin into hepatocytes. Available in Europe but not available in the United States. |
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| Adult Dose | 20-50 mg/kg/d IV for 48-96 h |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity |
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| Interactions | Reduces lipid peroxidase with coadministration of butyrophenones or phenothiazines |
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| Pregnancy | C - Safety for use during pregnancy has not been established.
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| Precautions | High doses decrease GI transit time |
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| Drug Name | Thioctic acid (Thiocid, Alpha Lipoic Acid) |
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| Description | It is a coenzyme in cellular metabolism, a free radical scavenger, and an antioxidant used for diabetic neuropathies and various metabolic disorders. No controlled trials exist. Clinical efficacy has not been proven. |
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| Adult Dose | 50-150 mg IV q6h; dilute in parenteral dextrose solution; not to exceed infusion rate of 50 mg/min |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; contains benzyl alcohol, do not use in neonates |
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| Interactions | May cause additive hypoglycemic effects with antidiabetic agents; antagonizes actions of cisplatin |
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| Pregnancy | C - Safety for use during pregnancy has not been established.
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| Precautions | Associated with hypoglycemia; protect thioctic acid from light; not available commercially for use in humans, though it may be available from chemical supply companies; parenteral product contains benzyl alcohol; may temporarily worsen existing neuropathy; rapid infusion associated with headache and respiratory depression |
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Further Inpatient Care
- Admit all cases of patients with A phalloides ingestion and observe for progression to later stages.
Further Outpatient Care
- Patients who remain asymptomatic for 12 hours after ingestion of unknown mushrooms may be discharged safely. Continue vigorous IV hydration and gastric decontamination.
- Monitor the following laboratory studies for signs of deterioration:
- Liver function tests
- Electrolytes and glucose
- BUN and creatinine
- Prothrombin time
Transfer
- Consider transferring any symptomatic patient to a facility with liver transplant capability to minimize delays in procuring an appropriate organ.
Deterrence/Prevention
- Closely monitor young children in rural or suburban areas.
Prognosis
- Prognosis most likely is determined by the quantity of mushroom that was eaten.
- A variation in individual susceptibility to the toxin appears to exist.
- Children absorb a larger dose of toxins per kilogram of body weight and have a higher mortality than adults.
Patient Education
- Educate the patient of the dangers of amateur mushroom hunting.
Medical/Legal Pitfalls
- Failure to consider A phalloides ingestion
- Eliminating the diagnosis of A phalloides because of an early (<6 h) onset of symptoms
- Failure to consider the ingestion of multiple species of mushrooms
- Discharging a patient with suspected A phalloides ingestion after resolution of gastrointestinal symptoms
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Toxicity, Mushrooms - Amatoxin excerpt Article Last Updated: Jun 21, 2006
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