Mushroom Toxicity 

Mushrooms are the fruiting bodies of a group of higher fungi that have evolved contemporaneously with plants for millions of years. Mushrooms are widely distributed throughout the world, and thousands of species have been identified.

About 100 species of mushrooms are poisonous to humans, and 15-20 mushroom species are lethal when ingested. No simple rule exists for distinguishing edible mushrooms from poisonous mushrooms. In more than 95% of mushroom toxicity (mushroom poisoning) cases, poisoning occurs as a result of misidentification of the mushroom by an amateur mushroom hunter. In fewer than 5% of the cases, poisoning occurs after the mushroom is consumed for its mind-altering properties.

The severity of mushroom poisoning may vary depending on the geographic location where the mushroom is grown, growth conditions, the amount of toxin delivered, and the genetic characteristics of the mushroom. Boiling, cooking, freezing, or processing may not alter the mushroom's toxicity. Variations in clinical effects may depend on an individual's susceptibility and on the presence of confounding factors such as contamination and/or co-ingestion. In general, children, older persons, and persons with disabilities are at a higher risk of developing serious complications with mushroom poisoning than are healthy young adults.

Mushroom poisoning occurs after the ingestion of toxins synthesized by the mushrooms themselves. Each poisonous mushroom species contains 1 or more toxins, which may be classified based on the mushroom's physiologic and clinical effects in humans, the target organ toxicity, and the time to symptom onset. The clinical spectrum and toxicity vary with the species consumed, the amount consumed, the season, the geographic location where the mushroom was grown, the preparation method, and an individual's response to the toxins.

Having reviewed the world's scientific literature on mushroom poisoning published from 1951-2002, Diaz classified mushroom poisoning into 3 major categories, depending on the time-to-symptom development.^[1] These categories include the following:

• Early symptom category: Symptoms generally appear within the first 6 hours of mushroom ingestion and include GI, allergic, and neurologic syndromes.
• Late symptom category: Signs and symptoms begin to appear between 6 and 24 hours after ingestion and may include hepatotoxic, nephrotoxic, and erythromelalgic syndromes.
• Delayed symptom category: Symptoms appear more than 24 hours after ingestion and include mostly nephrotoxic syndromes.

Mushroom toxins include the following:

• Cyclopeptides (ie, amatoxins, phallotoxins, virotoxins)
• Gyromitrins
• Orellanine
• Muscarine
• Psilocybin
• Muscimol/ibotenic acid
• Coprine
• Direct central neurotoxins
• Nephrotoxins
• Myotoxins
• Immunoactive toxins
• Hemolytic toxins
• GI irritants

In Japan, a recent outbreak of acute encephalopathy was noted among patients with renal dysfunction after eating autumn mushrooms.

GI poisons are the most frequently encountered mushroom toxins. Amatoxins, gyromitrins, and orellanine are the most commonly implicated toxins in fatal mushroom poisonings worldwide. The amatoxins and gyromitrins are hepatotoxic. Gyromitrins are also epileptogenic. Orellanine is nephrotoxic. Muscarine, psilocybin, muscimol, and ibotenic acid are nervous system poisons. Coprine causes a disulfiramlike reaction when combined with alcohol.

Cyclopeptides

These include amatoxins (high toxicity), phallotoxins (medium toxicity), and virotoxins (no toxicity).

Amatoxins, which are responsible for more than 95% of mushroom-related fatalities in the United States, are cyclic octapeptides that are synthesized by a number of Amanita species and several of their relatives, including some members of the Galerina, Lepiota, and Conocybe genera.

At least 5 subtypes of amatoxins are known, the 2 most significant being the alpha-amatoxin, which inhibits RNA polymerase II and protein synthesis, and the beta-amatoxin. Alpha-amatoxin and beta-amatoxin are rapidly absorbed by the GI tract, have limited protein binding, and may undergo enterohepatic recirculation. Both are excreted in the urine and may be detected in the vomitus and feces.

Hepatocellular damage is presumably caused by the formation of free radical intermediates.

Amanita phalloides (death cap), Amanita virosa (destroying angel), Amanita verna (fool's mushroom), and Galerina autumnalis (autumn skullcap) are the best known and the deadliest amatoxin-containing mushrooms. See the image below.

Gyromitrins

Gyromitrin is a volatile hydrazine derivative synthesized by certain species of false morel (ie, Gyromitra esculenta, Gyromitra ambigua, Gyromitra gigas, Gyromitra infula) and early false morel (Verpa bohemica). Gyromitrin poisoning typically occurs after ingestion of the toxin-containing mushrooms but may also result from inhalation of the cooking vapors during their preparation.

In the stomach, gyromitrin is rapidly hydrolyzed into acetaldehyde and N -methyl-N -formyl hydrazine (MFH), which is then slowly converted to N -methylhydrazine (MH). Both MFH and MH are toxic to humans. MFH inhibits a number of hepatic systems, including the cytochrome P-450 and glutathione, and causes hepatic necrosis. Hepatocellular damage is presumably caused by the formation of free radical intermediates. MH inhibits pyridoxine kinase and interferes with all the pyridoxine-requiring enzymes in the body, including those involved in the synthesis of GABA. The reduction of GABA in the brain leads to CNS hyperexcitability and convulsions. Gyromitrin ingestion may also result in methemoglobinemia, hemolysis, and renal failure.

Orellanine

Orellanine is a nephrotoxic compound that is synthesized by a number of species of the Cortinarius mushrooms. Orellanine-containing mushrooms include Cortinarius orellanus (webcap) and Cortinarius speciosissimus, both of which are commonly found in Europe and Japan but not in North America. North American Cortinarius species that contain orellanine include Cortinarius gentilis, Cortinarius callisteus, Cortinarius rainierensis, and Cortinarius splendens. The gentilis species is most commonly implicated in orellanine poisoning in the United States.

Orellanine is colorless and crystalline in nature and may be converted into orelline, which itself may be toxic. Its main effects are on the renal tubular system, where it causes necrosis with relative sparing of the glomerular apparatus. Fatty degeneration of the liver and severe inflammatory changes in the intestine may accompany the renal damage. The Cortinarius mushrooms also may elaborate other compounds, such as cortinarin A, B, and C, which exhibit a nephrotoxic potential in laboratory animals.

Other mushrooms such as Amanita smithiana and Amanita proxima have also been associated with an acute oliguric renal failure that requires temporary hemodialysis. Norleucine has been identified as the nephrotoxin found in A smithiana that causes renal tubular damage.

Psilocybin

Psilocybin and psilocin are elaborated by a number of mushroom genera, including Psilocybe, Panaeolus, Gymnopilus, Copelandia, Conocybe, Psathyrella, and Pluteu. Psilocybin and psilocin are serotonin (5-HT2) agonists and, when ingested, cause psychedelic effects similar to those of lysergic acid (LSD).

Ibotenic acid/muscimol

Amanita muscaria (fly agaric) and Amanita pantherina (panthercap) mushrooms synthesize ibotenic acid and muscimol, which are hallucinogenic. Ibotenic acid is structurally similar to glutamic acid and acts as an agonist at the glutamic acid receptors in the CNS. Ibotenic acid may also be decarboxylated in vivo to muscimol, thus increasing the muscimol effect of the mushroom. Muscimol is structurally similar to GABA and acts as a GABA-receptor agonist. These mushrooms also contain significant amounts of anticholinergic substances and small amounts of muscarine.

Muscarine

Muscarine is a quaternary amine that is elaborated by a number of Inocybe and Clitocybe mushroom species. Muscarine stimulates the peripheral muscarinic nervous system without affecting nicotinic cholinergic activity in the CNS. Ingestion of mushrooms with high concentrations of muscarine, such as Clitocybe dealbata (sweater mushroom) and Inocybe geophylla, results in muscarine poisoning.

Coprine

A few species of mushrooms, including the Coprinus atramentarius (inky cap) mushroom, produce coprine, an amino acid that is metabolized to 1-aminocyclopropanol in the human body. This metabolite blocks acetaldehyde dehydrogenase, and, in the presence of alcohol, acetaldehyde builds up, resulting in a disulfiram reaction. The effects of 1-aminocyclopropanol may last as long as 72 hours after ingestion of the mushroom.

Involutin

Ingestion of Paxillus involutus may result in an acute onset of abdominal pain, nausea, vomiting, and diarrhea within 30 minutes to 3 hours of ingestion, followed by an immune complex-mediated hemolytic anemia with hemoglobinuria, oliguria, anuria, and acute renal failure.

Lycoperdon-associated pneumonitis

An immune reaction is believed to be the cause of the bronchoalveolar allergic syndrome, which is seen after inhalation of spores of some puffball mushroom species.

GI toxins

Hundreds of mushrooms contain toxins that can cause GI symptoms (eg, nausea, vomiting, diarrhea, abdominal pain) similar to those observed with more dangerous mushrooms. They include Chlorophyllum molybdates (green gill), Omphalotus illudens (jack-o'-lantern), Boletus piperatus (pepper bolete), and Agaricus arvensis (horse mushroom), among many others.

Frequency

United States

Accidental poisonings tend to occur most commonly in the spring and fall, when mushroom species are at the peak of their fruiting stage.

In general, most ingestions result in minor GI illness, with only the most severe requiring medical attention. Because the number of unreported cases is unknown, accurate figures regarding the frequency of mushroom poisoning are difficult to obtain. Cases usually are sporadic, and a few outbreaks have been reported.

In the American Association of Poison Control Centers National Poison Data System 2008 Annual Report, 6034 mushroom exposures were reported in the United States (a slight decrease from the prior year), with 2367 treated in a health care facility and no fatalities.^[2]

International

Mushroom foraging is common in Russia and Europe; however, accurate figures regarding the incidence of mushroom toxicity (mushroom poisoning) are difficult to obtain. Outbreaks of severe mushroom poisoning have occurred in Europe, Russia, the Middle East, and the Far East. In April of 2008, an outbreak of mushroom poisonings in the Upper Assam part of India claimed more than 30 lives.

Mortality/Morbidity

Morbidity and mortality rates depend on the patient's age and general health. Children and elderly persons are at the greatest risk for toxicity. Rapid diagnosis and treatment also significantly alter mortality rates. In the case of amatoxins, the mortality rate, which has been quoted to be 50-60%, may be reduced to well below 10%. Of the 5644 single mushroom exposures reported to US poison control centers in 2008, 39 major outcomes occurred, and 4 deaths were reported.^[2]

Age

Children and elderly patients are at the greatest risk for toxicity. In a report by the North American Mycological Association (NAMA) Case registry, mushroom toxins may also be transferred to nursing infants through mothers' milk.^[3] According to the American Association of Poison Control Centers National Poison Data System 2008 Annual Report, 3144 out of 5644 total single mushroom exposures were reported in those younger than 6 years; 1157 mushroom exposures were reported in individuals aged 6-19 years, and 1144 were reported in individuals older than 19 years.^[2]