INTRODUCTION	Section 2 of 10
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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. While 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 US 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.

Mushroom toxidromes may be classified according to toxin and clinical presentation. Mushroom toxins have been divided into the following 7 main categories:

• Amatoxins (cyclopeptides)

• Orellanus (Cortinarius species)

• Gyromitrin (monomethylhydrazine)

• Muscarine

• Ibotenic acid

• Psilocybin

• Coprine (disulfiramlike)

Some authors have created an eighth category comprising a vast range of species that only cause gastrointestinal symptoms.

Amanitin phalloides syndrome or Mycetismus choleriformis accounts for 90-95% of all fatalities from mushroom poisoning in North America. 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.

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, and cooking fumes from certain species can cause poisoning.

Pathophysiology: Each mushroom group exerts its toxic effect by a different mechanism, and certain toxins have a predilection for individual organ systems. The amatoxins (cyclic octapeptides), which include amanitin, verotoxin, and phalloides, cause severe hepatocellular damage by inhibiting RNA polymerase II, thereby inhibiting protein synthesis at the cellular level, causing cell death. Other organ systems with high turnover rates (eg, gastrointestinal tract, kidneys) also are affected severely. Ibotenic acid and muscimol bind to glutamic acid and GABA receptors, respectively, and thereby interfere with CNS receptors. Monomethylhydrazine (MMH) from gyromitrin-containing mushrooms affects the GI tract, liver, and kidneys by inhibiting pyridoxine-dependent pathways in the synthesis of GABA. Muscarine 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. Coprine
inhibits aldehyde dehydrogenase, producing a disulfiramlike reaction in those consuming ethyl alcohol. Psilocybin indole exerts its effect on the central nervous system by stimulation of serotonin receptors. 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.

Frequency:

• In the US: 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. In 1999, the American Association of Poison Control Centers reported 8996 mushroom exposures with 2930 treated in a health care facility and 6 fatalities.

Mortality/Morbidity: Mortality rate is estimated at 0.016%.

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 Toxic Exposure Surveillance System of the American Association of Poison Control Centers' 1999 report, 5976 mushroom ingestions were reported in those younger than 6 years.

	CLINICAL	Section 3 of 10
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

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.

• A short latency period (30-180 min) may be observed with GI mushroom (eg, Chlorophyllum molybdates, Entoloma lividum, Boletus species, Paxillus species) syndromes, muscarine-containing mushrooms (Inocybe species, Clitocybe species), psilocybin-containing mushrooms (Paneolus species, Psilocybe species, Gymnopilus species), and coprine-containing mushrooms.

• GI mushroom syndromes present exclusively with abdominal discomfort, cramping, nausea, vomiting, and/or diarrhea. Dehydration is the most common complication. Most symptoms resolve by 24 hours and the prognosis is generally good.

• Anticholinergic symptoms can occur with ibotenic and muscimol ingestions. Dizziness, incoordination, ataxia, GABAergic effects, seizures, hallucinations, muscle spasms, flushing, and dilated pupils may be observed.

• Cholinergic effects may result 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.

• Neuropsychiatric symptoms, including hallucinations or delirium, have been associated with mycetism caused by ibotenic acid, muscimol, and psilocybin. Muscle weakness, drowsiness, hallucinations, hyperkinesis, and mydriasis have been described. Patients may have hallucinations while awake and then have a prolonged sleep that lasts hours; in each case, the prognosis is generally good and symptoms resolve within 24 hours with supportive care. Rare residual effects have been reported.

• Muscarine and coprine intoxications have also been associated with neurovegetative symptoms.

• The Coprinus syndrome 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 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.

• Amatoxin toxicity presents 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.

• Orellanine toxicity initially may present with gastrointestinal dysfunction 24-48 hours postingestion of mushrooms from the genus Cortinarius. Acute renal failure may follow from 36 hours to 2 weeks postingestion and present with flank pain, polydipsia, polyuria, oliguria, and malaise.

• Gyromitrin toxicity typically presents 6-10 hours postingestion (but may be delayed up to 48 h) with gastrointestinal dysfunction. Patients may display symptoms and signs of volume depletion, hepatic injury, methemoglobinemia, intravascular hemolysis, and CNS effects (eg, malaise, tremor, myoclonus, delirium, seizures, encephalopathy).