eMedicine Specialties > Emergency Medicine > Toxicology

Toxicity, Mushrooms

Author: Karen Jubanyik, MD, Assistant Professor, Section of Emergency Medicine, Department of Surgery, Yale University School of Medicine; Consulting Staff, Yale-New Haven Hospital
Coauthor(s): Kimberly L Nicoll, MD, Staff Physician, Section of Emergency Medicine, Yale New Haven Hospital
Contributor Information and Disclosures

Updated: Apr 8, 2009

Introduction

Background

Mushroom toxicity is a worldwide concern. The increased use of mushrooms as components of organic diets, for alternative therapies, and by unsupervised children accounts, in part, for the renewed interest in mycetism. Use of mushrooms as recreational drugs also accounts for a significant number of exposures, especially in the adolescent population. Although most mushroom ingestions do not cause a clinically significant toxidrome, the lethal potential of a select few make mushroom toxicity an important subject. The incidence of mushroom poisoning in the United States peaks in accordance with regional mushroom growing seasons, and case frequency has increased on the West Coast. Ingestion is the most common route of entry, but intravenous injection of mushroom toxins and inhalation of mushroom spores have been reported.

Multiple clinical syndromes have been described with mushrooms. Because of the large number of mushroom species and their toxicities, multiple classifications were attempted in order to ease diagnostic recognition and appropriate treatment and disposition. The most important part in treating patients who used mushrooms is to recognize exposures that are associated with serious outcome. 

Mushrooms can be classified by the onset of symptoms (early: less than 6 h; late: between 6 and 24 h; and delayed: equal to or greater than 1 d), by target organ toxicity, or by major chemical component that is responsible for the toxic effect.

Allergic reaction is the most common complication associated with mushroom use, and, seldom, it can progress to frank anaphylaxis. Majority of "toxic" mushroom exposures will result only in mild gastrointestinal symptoms.

Early-onset syndromes include neurotoxic, gastrointestinal and allergic presentation. The syndromes with late presentation can present with hepatotoxicity, accelerated nephrotoxicity, and erythromelalgia. Delayed nephrotoxic, delayed neurotoxic, and rhabdomyolysis constitute the group of delayed syndromes.

Exposure to cyclopeptide-containing mushrooms accounts for 90-95% of all fatalities from mushroom poisoning in North America. The common mushrooms responsible for this syndrome include Amanita phalloides (death cap), Amanita virosa (destroying angel), and Galerina autumnalis. These mushrooms are found on all continents, except Antarctica, even in urban yards. Many poisonous mushrooms are not unique in appearance and bear a close resemblance to nonpoisonous varieties. This discussion follows a clinical format because the offending mushroom is frequently unavailable for identification and poisoning may occur from a single species or a combination of different species. Trestrail's data indicate that the mushroom was available for identification in only 3.4% of exposures.¹

Query patients presenting to the emergency department with compatible clinical scenarios about mushroom ingestion. Even a small piece of a toxic mushroom may cause death. Cooking, salting, or drying does not inactivate all mushroom toxins (amatoxins are heat-stable), and cooking fumes from certain species can cause even more toxicity than the ingested mushroom.

Pathophysiology

Each mushroom group exerts its toxic effect by a different mechanism, and certain toxins have a predilection for individual organ systems.  

• Allenic norleucine (2-amino-4,5-hexadienoic acid) is solely found in Amanita smithiana, and it is a renal epithelial toxin.² It causes early gastrointestinal symptoms (similar to less toxic mushroom exposures), and delayed renal failure (within 4-6 d).
• The amatoxins, phallotoxins, and virotoxins (bicyclic octapeptides) can cause severe hepatocellular damage by inhibiting RNA polymerase II, thereby inhibiting protein synthesis at the cellular level. This leads to hepatocyte death and may cause irreversible fulminant hepatic failure. Other organ systems with high turnover rates (eg, gastrointestinal tract, kidneys) also are affected severely. For more detailed information on this mushroom group, see eMedicine article Toxicity, Mushroom - Amatoxin.
• Coprine-containing mushrooms (Coprinus atramentarius, Coprinus insigis) exert their effect through a coprine metabolite, 1-aminocyclopropanol. 1-Aminocyclopropanol inhibits aldehyde dehydrogenase, producing a disulfiramlike reaction in those consuming ethyl alcohol (eg, flushing, headache, palpitations, chest pain, orthostatic hypotension).
• The toxin gyromitrin found in some mushrooms is hydrolyzed in vivo to monomethylhydrazine (MMH). MMH, used as a solvent and as rocket fuel, is chemically related to isoniazid and interferes with pyridoxine-dependent enzymes and affects the GI tract, liver, and kidneys, as well as the central nervous system (coma, seizures). It also can cause hemolysis and methemoglobinemia.
• Ibotenic acid and muscimol bind to glutamic acid and GABA receptors, respectively, and thereby interfere with CNS receptors causing hallucinogenic and mild anticholinergic symptoms.
• Muscarine is quaternary ammonium compound that affects the autonomic nervous system. It acts through depolarization of muscarinic acetylcholine receptors and exerts a peripheral cholinergic effect through stimulation of the postganglionic parasympathetic receptors. Muscarine does not crossthe blood-brain barrier to cause central cholinergic effects.
• Orellanine and orelline, the bipyridyl toxins isolated from Cortinarius orellanus, exhibit their nephrotoxic effects by inhibiting alkaline phosphatase of the proximal tubule cells. Genetic factors may contribute to the clinical manifestations of this toxin, which has toxicity that is not reduced by cooking or drying.
• Psilocybin compounds are similar in structure to LSD; they share an indole backbone and likely act by stimulating serotonin receptors causing hallucinations and mild sympathomimetic effects.

Frequency

United States

Incidence of mushroom toxicity is reported to be 5 exposures per 100,000 population per year. According to a 12-year study by Goldfrank et al, more than 50% of patients experienced no symptoms, 25% were treated in a health care facility, 10-15% had minor symptoms, less than 5% had moderate symptoms, and 0.2% suffered major toxicity.³ In the American Association of Poison Control Centers National Poison Data System 2007 Annual Report, 7351 single mushroom exposures were reported, with 2634 treated in a health care facility and no fatalities.⁴

International

Reports of mushroom exposures have been increasing worldwide. Mushrooming is a popular leisure activity in much of Europe, and several hundred deaths annually are attributed to mushroom toxicity. Most exposures were acute and unintentional. The popularity in Japan of the Tricholoma magnivalere (matsutake mushroom or pine mushroom) has led to an increased number of poisonings from a look-alike poisonous variety that grows wild in the Pacific Northwest, Amanita smithiana. Patients present within 30 minutes to 12 hours of ingestion and typically are oliguric and anuric at presentation and may develop acute renal failure, requiring hemodialysis for up to a month.  

Mortality/Morbidity

Of the 7351 single mushroom exposures reported to US poison control centers in 2007, 35 major outcomes occurred and no deaths were reported.⁴

Race

No scientific data have found that outcomes of mushroom toxicity are dependent on race.

Sex

No scientific data have found that outcomes of mushroom toxicity are dependent on sex.

Age

According to the American Association of Poison Control Centers National Poison Data System 2007 Annual Report, 4543 out of 7351 total single mushroom exposures were reported in those younger than 6 years; 1352 mushroom exposures were reported for those aged 6-19 years and 1189 were reported for those older than 19 years.⁴

Clinical

History

Try to ascertain the species or varieties of the wild mushrooms ingested, the type of preparation, volume ingested, and symptoms of others sharing the mushroom meal. Comorbidity, concomitant medications, allergies to medications, and drug and alcohol use may influence the clinical picture and should be elicited. Symptoms and signs are discussed relative to onset postingestion, with gastrointestinal dysfunction being a nearly universal component. Early symptoms may be observed with mixed ingestions, and they do not exclude a potentially fatal poisoning. Resources that may be helpful in identifying mushroom species include poison control centers, mycologists, and Poisindex.

• Amatoxins  
  • Distinct delay in presentation (5-24 hours after exposure) is one of the most important clues in recognition of this  life-threatening syndrome. It can be classified as "long latency syndrome."
  • As mentioned before, mortality is very high and can range from 20-25%.
  • Amatoxin toxicity can present in the following 3 stages.
    • Stage one presents with abdominal cramping, nausea, vomiting, and profuse watery diarrhea after a latent period of 6-12 hours.
    • The second stage begins with clinical recovery of gastrointestinal dysfunction after 24 hours and lasts 2-3 days, during which liver damage is ongoing.
    • In the third stage, hepatic and renal damage becomes clinically evident.
• Gyromitrin
  • Gyromitrin is hydrolyzed to monomethylhydrazine (MMH), which is responsible for CNS toxicity.
  • Gyromitrin toxicity typically presents 6-10 hours postingestion (but may be delayed up to 48 h) with gastrointestinal dysfunction.
  • The typical mushroom, Gyromitra esculenta, or false morel, has an irregular convoluted cap with a brainlike appearance.
  • Because of the volatility of the MMH, vapors can be even more toxic to the person who cooks the mushroom than to those who subsequently ingest the mushrooms.  
  • Patients may display symptoms and signs of volume depletion, hepatic injury, methemoglobinemia, intravascular hemolysis, and CNS effects (eg, malaise, tremor, myoclonus, delirium, seizures, encephalopathy).
  • Very rarely does this mushroom cause fatalities.
• Orelline and orellanine
  • Orellanine toxicity initially may present with gastrointestinal symptoms 24-48 hours postingestion of mushrooms from the genus Cortinarius (C orellanus, C splendens).
  • Acute renal failure secondary to focal tubular damage and fibrosis with glomerular sparing may follow from 36 hours to 20 days postingestion, and it can present with flank pain, polydipsia, polyuria, oliguria, and malaise.
  • Patients may require hemodialysis; however, mortality is rare.
• Gastrointestinal irritants
  • Mushrooms associated with a GI toxidrome present exclusively with abdominal discomfort, cramping, nausea, vomiting, and/or diarrhea.
  • Dehydration is the most common complication.
  • Most symptoms resolve within 24 hours, and the prognosis is generally good.
• Ibotenic acid and muscimol
  • Symptoms may develop within 30-90 minutes and are similar to those seen with ethyl alcohol ingestions.
  • Mild anticholinergic symptoms can occur after exposure to ibotenic acid and muscimol. They can act on GABA receptors causing hallucinogenic effects. Common mushrooms in this group include Amanita muscaria and Amanita pantherina.
  • Because the toxins are excreted unaltered in the urine, it is not uncommon for people to drink urine for a second dose in intentional ingestions. 
  • Dizziness, poor coordination, ataxia, seizures, hallucinations, muscle spasms, flushing, and dilated pupils may be observed.
• Muscarine
  • Mushrooms in this group include Clitocybe dealbata, Inocybe fastigiata, and Inocybe purico.
  • Cholinergic effects may result within 2 hours from muscarine ingestion.
  • Perspiration, salivation, lacrimation, blurred vision, miosis, hypotension, bradycardia, and bronchoconstriction have been described.
  • Although muscarine was first isolated from the Amanita muscaria mushroom in 1868, the signs and symptoms of poisoning from A muscaria are not related to muscarine. 
  • A common source of muscarine toxicity worldwide is the Omphalotus olearius (orange luminous jack-o-lantern), often mistaken for the edible chanterelle.
• Psilocybin and psilocin
  • Psilocybin-containing mushrooms cause symptoms within one hour, typically perceptual changes of altered or heightened awareness (hearing colors or seeing music), rather than true hallucinations. 
  • The prognosis is generally good, and symptoms resolve within 24 hours with supportive care. Cases of prolonged psychosis or temporary paralysis following overdose have been reported. Seizures and hyperthermia have been reported, with a symptom constellation not unlike serotonin syndrome.
  • Muscarine and coprine intoxications have also been associated with neurovegetative symptoms.
• Coprine
  • The coprinus syndrome (from Coprinus atramentarius or "inky cap") is characterized by a rapid onset of nausea, vomiting, tachycardia, palpitations, paresthesias, diaphoresis, and flushing. Hypotension also can occur. This syndrome has been referred to as a disulfiramlike reaction; it is associated with ethanol use from 30 minutes to 5 days following a mushroom meal, and symptoms generally last 2-4 hours. Interestingly, if alcohol is consumed at the time of the mushroom meal, symptoms may not occur.
  • Intravenous injection of mushroom toxins from Psilocybe species has been reported. The clinical course includes vomiting, fever, muscle cramps, and hypoxia.
• A short latency period (30-180 min) may be observed with mushrooms (eg, Chlorophyllum molybdates, Entoloma lividum, Boletus species, Paxillus species) associated with GI symptomatology only as well as with muscarine-containing mushrooms (Inocybe species, Clitocybe species), psilocybin-containing mushrooms (Paneolus species, Psilocybe species, Gymnopilus species), and coprine-containing mushrooms. 
• A long latency period (>6 h) can be observed with amatoxins, orellanus, and gyromitrin syndromes. This generally signifies a serious ingestion and should be considered potentially life threatening.

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