eMedicine Specialties > Emergency Medicine > Toxicology

Toxicity, Mushroom

Rania Habal, MD, Assistant Professor, Department of Emergency Medicine, New York Medical College
Jorge A Martinez, MD, JD, Clinical Professor, Department of Internal Medicine, Louisiana State University School of Medicine; Clinical Instructor, Department of Surgery, Tulane School of Medicine

Updated: Jun 25, 2009

Introduction

Background

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.

Pathophysiology

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.
  
  

  

  Amanita phalloides.

  
  
• 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 2007 Annual Report, 7351 mushroom exposures were reported in the United States, with 2634 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 7351 single mushroom exposures reported to US poison control centers in 2007, 35 major outcomes occurred, and no 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 2007 Annual Report, 4543 out of 7351 total single mushroom exposures were reported in those younger than 6 years; 1352 mushroom exposures were reported in individuals aged 6-19 years, and 1189 were reported in individuals older than 19 years.²

Clinical

History

Patient history is the most important aspect of the diagnosis. Without eliciting a history of ingestion, the diagnosis of mushroom poisoning cannot be made. Although this may be inconsequential for most mushroom ingestions, it is detrimental for mushrooms containing amatoxin, orellanine, and gyromitrin because the early removal of these toxins from the GI tract drastically alters the outcome of the case. Every effort should be made to identify the mushroom or mushrooms early. If a sample mushroom is available, use of telemedicine and the Internet may prove valuable in identifying the mushroom. If a sample mushroom is not available, questioning patients and their family about the identity of the mushroom they thought they were picking may narrow the list of possibilities.

The history also should include (1) the time of ingestion, (2) time to onset of symptoms, (3) the amount of mushrooms ingested, (4) whether other people ingested the same mushrooms, and (5) whether the meal included other mushroom species. Because patients often mix mushrooms, symptoms from one type of mushroom may mask or overlap with symptoms from another type of mushroom, thus making identification even more difficult.

Mushrooms are best classified by the physiologic and clinical effects of their poisons. The traditional time-based classification of mushrooms into an early/low toxicity group and a delayed/high toxicity group may be inadequate. Additionally, many mushroom syndromes develop soon after ingestion. For example, most of the neurotoxic syndromes, the Coprinus syndrome (ie, concomitant ingestion of alcohol and coprine), the immunoallergic and immunohemolytic syndromes, and most of the GI intoxications occur within the first 6 hours after ingestion.

Ingestions most likely to require intensive medical care involve mushrooms that contain cytotoxic substances such as amatoxin, gyromitrin, and orellanine. Mushrooms that contain involutin may cause a life-threatening immune-mediated hemolysis with hemoglobinuria and renal failure. Inhalation of spores of Lycoperdon species may result in bronchoalveolitis and respiratory failure that requires mechanical ventilation.

Mushrooms that contain the GI irritants psilocybin, ibotenic acid, muscimol, and muscarine may cause critical illness in specific groups of people (eg, young persons, elderly persons). Hallucinogenic mushrooms may also result in major trauma and require care in an intensive care setting. Lastly, coprine-containing mushrooms cause severe illness only when combined with alcohol (ie, Coprinus syndrome).

• Amanita poisoning
  • Poisoning is characterized by a latent period of 6-12 hours after ingestion (range 6-48 h), during which the patient is asymptomatic.
  • At the end of this latent period, a sudden and severe gastroenteritislike illness phase occurs. The patient experiences abdominal pain, vomiting, and profuse watery diarrhea, which may lead to severe dehydration, electrolyte abnormalities, and, rarely, circulatory collapse in young and elderly persons. This phase, which may last as long as 2-3 days, is followed by an apparent recovery phase characterized by an apparent clinical improvement; however, an asymptomatic rise in hepatic enzyme levels signifies the onset of hepatic necrosis.
  • The third phase of amanita poisoning, ie, the hepatorenal syndrome, is characterized by jaundice, hypoglycemia, coma, and multiorgan and system failure followed by death in 50-90% of patients. With therapy, mortality may be well below 10%. The course of amatoxin poisoning typically lasts 6-8 days in adults and 4-6 days in children.
• Gyromitrin poisoning
  • The initial phases of poisoning resemble those of amatoxin poisoning and are characterized by a latent period of 6-10 hours after ingestion (range 3-48 h).
  • At the end of this latent period, the patient experiences a sudden onset of headache, abdominal cramping, vomiting, and diarrhea, which are generally self-limited. In patients who are young, elderly, or who are undergoing isoniazid therapy, this phase may be followed by monomethylhydrazine-related CNS symptoms such as vertigo, delirium, convulsions, and coma. If the toxin has been inhaled, the first phases are usually bypassed and the patient may exhibit CNS toxicity within 2 hours of the exposure. Hematologic, renal, and hepatic toxicities may also occur, followed by recovery. Hepatotoxicity is heralded by an elevation of transaminase levels, followed by signs and symptoms of hepatic insufficiency, and, rarely, death.
  • Recovery typically begins 2 days after the onset of symptoms but may last as long as 5 days. In a small number of patients, the course may be fulminant, accounting for a 2-4% mortality rate.
• Orellanine poisoning: Poisoning begins with a seemingly minor GI illness characterized by mild nausea, vomiting, and, sometimes, diarrhea lasting 24-48 hours after ingestion. This phase is followed by a prolonged latent period lasting from 3 days to 3 weeks. An intense thirst and polyuria herald renal failure. The patient also may experience headaches, myalgias, muscle cramps, loss of consciousness, and convulsions. Dialysis may be required in as many as 50% of the patients, and death may occur in 15% of the cases.
• Psilocybin poisoning: The onset of hallucinations is usually rapid, and the effects generally subside within 2 hours. Poisoning by these mushrooms is rarely fatal in adults and may be distinguished from ibotenic acid poisoning by the absence of drowsiness or coma. The most severe cases of psilocybin poisoning occur in small children, in whom large doses may cause hallucinations accompanied by fever, convulsions, coma, and death.
• Muscarine poisoning: Poisoning is characterized by increased salivation, perspiration, and lacrimation within 15-30 minutes of mushroom ingestion. With large doses, patients may experience abdominal pain, severe nausea, diarrhea, blurred vision, and labored breathing. Intoxication generally subsides within 2 hours. Death is rare but may result from cardiac or respiratory failure in severe cases.
• Ibotenic acid/muscimol poisoning: Symptoms generally occur within 1-2 hours of mushroom ingestion. In children, ibotenic-acid effects (glutaminergic) may predominate. These effects include hyperactivity, excitability, illusions, delirium, and convulsions. In adults, muscimol GABAergic effects may predominate and include drowsiness, dysphoria, and vertigo (sometimes accompanied by sleep). Periods of drowsiness may alternate between periods of hyperactivity and periods of delirium. Symptoms generally last for a few hours. Fatalities rarely occur in adults, but, in children, accidental consumption of large quantities of these mushrooms may cause convulsions, coma, and other neurologic problems for as long as 12 hours.
• Coprine poisoning: The digestion of coprine-containing mushrooms generates a metabolite that inhibits acetaldehyde dehydrogenase. Therefore, these mushrooms cause symptoms to occur only when alcoholic beverages are consumed within 2 hours of ingestion. Symptoms include headache, nausea, vomiting, flushing, chest pain, and diaphoresis typical of the disulfiram syndrome and may last for 2-3 hours.
• Miscellaneous GI poisons: Many toxic mushrooms (poisonous mushrooms) produce symptoms that are similar to those caused by the deadly protoplasmic poisons. Some mushrooms may cause vomiting, diarrhea, or both that last for several days. Fatalities caused by these mushrooms are rare and are due to dehydration and electrolyte imbalances caused by diarrhea and vomiting; fatalities occur especially in debilitated, very young, or very old patients. Replacement of fluids and other appropriate supportive therapy prevents death in these cases.
• Paxillus syndrome may occur following the ingestion of P involutus. This syndrome begins with gastroenteritislike symptoms within 3 hours of ingestion, followed by an acute hemolytic anemia with hemoglobinuria and renal failure.
• Bronchoalveolar allergic syndrome may follow the inhalation of spores of puffball mushroom species. This syndrome begins with a nasopharyngitis, which is followed by worsening respiratory symptoms, including dyspnea, cough, fever, and malaise, which may progress to respiratory failure.
• A proxima toxicity is characterized by a latent phase that lasts 12-24 hours, followed by an initial gastroenteritislike illness, with nausea, vomiting, and diarrhea. Oliguric renal failure occurs several days after the ingestion.
• A smithiana toxicity, which begins 30 minutes to 12 hours after the ingestion, is characterized by nausea, vomiting, diarrhea, malaise, and dizziness and is followed by oliguric renal failure. This mushroom has also been associated with hepatotoxicity.

Physical

The physical findings depend on the type of mushroom ingested.

• Cyanosis may be secondary to hypoxia from any cause but may occur with gyromitrin poisoning. Gyromitrin poisoning causes methemoglobinemia and, occasionally, may occur after an intravenous injection of psilocybin.
• Facial flushing may be a manifestation of anticholinergic poisoning and may be noted in a patient's coprine-related disulfiram (Antabuse) reaction.
• Jaundice may be observed in patients with liver failure due to gyromitrin and amatoxin poisoning. Jaundice may also be a manifestation of hemolysis, rarely seen with Paxillus ingestion.
• Fever may be seen with psilocybin and muscimol poisonings.
• Tachycardia is nonspecific, may be seen with any of the mushrooms, or may be a manifestation of hypoxia or hypovolemia from any cause.
• Bradycardia may be a manifestation of muscarine poisoning.
• Mydriasis is commonly observed with ingestion of mushrooms that contain psilocybin and muscimol (because they also contain anticholinergic substances).
• Miosis is observed with toxicity caused by muscarine-containing mushrooms.
• Toxidromes
  • A few of the toxic mushrooms may exhibit a known toxidrome, permitting early diagnosis and treatment. A cholinergic toxidrome may occur with mushrooms that contain muscarine. Patients present early with a so-called SLUDGE (salivation, lacrimation [with blurred vision and miosis], increased urinary frequency, diarrhea, GI distress, emesis) reaction. Severe poisoning may also result in cardiotoxicity manifested as bradycardia and hypotension. In addition, severe bronchorrhea may lead to respiratory failure.
  • An anticholinergic syndrome may occur with the ingestion of hallucinogenic mushrooms. An anticholinergic syndrome is characterized by fever, tachycardia, agitation, hallucination, hypertension, skin flushing, dry mucous membranes, mydriasis, and blurred vision.
  • Patients with muscimol-induced GABAergic syndrome present with lethargy, ataxia, dysarthria, sleep, and coma.
  • A glutaminergic syndrome may be seen with ibotenic acid poisoning and presents with hallucinations, hyperactivity, ataxia, myoclonic jerks, and convulsions.
  • Because several mushrooms contain both muscimol and ibotenic acid, their ingestion generally results in alternating excitatory and inhibitory symptoms.
• Central nervous system
  • Hallucinations may be caused by poisoning from mushrooms that contain muscimol, ibotenic acid, psilocybin, and psilocin.
  • Convulsions may be secondary to hypoxia and shock but may also be caused by poisoning from mushrooms that contain gyromitrin, psilocybin, and isoxazole.
  • Coma may be secondary to hypoxia, hypoglycemia, and hypovolemia but may also be caused by hepatic encephalopathy due to poisoning with amatoxin and gyromitrin.
  • Muscle fasciculations are commonly observed in poisoning from mushrooms that contain muscarine.
• Gastrointestinal symptoms and hepatotoxicity
  • Early onset of GI symptoms and diarrhea (rarely) leading to dehydration commonly occurs with the ingestion of nonlethal toxic mushrooms.
  • Delayed GI symptoms, with vomiting and profuse diarrhea leading to shock, may occur with the ingestion of mushrooms that contain amatoxins and gyromitrins. These mushrooms are also hepatotoxic and may result in fulminant hepatic failure. Hepatomegaly and hepatic tenderness may signal the onset of hepatic failure and may be followed by encephalopathy, coma, bleeding, diatheses, cerebral edema, hepatorenal syndrome, and death.

Causes

Accidental poisoning accounts for more than 95% of the cases of mushroom intoxications and generally is due to the ingestion of a misidentified species of mushroom. Misidentification occurs despite significant variations between the species because they exhibit enough similarities to confuse the inexperienced mushroom hunter. The remaining cases are due to the intentional ingestion of the mushrooms for their mind-altering properties.

• Cyclopeptide poisoning commonly is due to Amanita species (ie, bisporigera, ocreata, phalloides, tenuifolia, virosa, verna) and Galerina species (ie, autumnalis, marginata, venenata). Less commonly, poisoning is due to Amanita species (ie, hygroscopica, suballiacea, verum), Clitocybe species (ie, cerrusata, dealbata, illudens), Galerina species (ie, badipes, beinrothii, fasciculata, micolor, sulciceps), Lepiota species (ie, brunneoincartata, citrophylla, clypeolarioides, heimii, helveola, josserandii, pseudohelveola, rufescens, subincarnata), Omphalotus olearius, and Pholiotina filaris.
• Monomethylhydrazine poisoning commonly is due to Gyromitra species (ie, ambigua, esculenta, infula). Also included in this group are the following Gyromitra species: brunnea, californica, caroliniana, fastigiata, and gigas.
• Orellanine poisoning is commonly due to C orellanus, Cortinarius speciosissimus, C gentilis, Cortinarius splendens, Cortinarius venenosus, and C rainierensis. Amanita Smithiana was once thought to contain orellanine, but the nephrotoxin in this species is in fact not known.
• Psilocybin and psilocin poisoning commonly are due to many Psilocybe species (ie, pelliculosa, semilenciata, caerulipes, cubensis), among others, but it also may be due to the ingestion of many Panaeolus species, some Amanita species, some Gymnopilus species (ie, spectabilis), and some Stropharia species. Psathyrella foenisecii and Psathyrella sepulchlaris are also common causes of psilocybin intoxication.
• Ibotenic acid and muscimol poisonings are commonly due to Amanita species (ie, A gemmata, A muscaria, A pantherina, A cokeri). Panaeolus campanulatus and Tricholoma muscarium also contain isoxazole derivatives.
• Muscarine poisoning is commonly due to Clitocybe species (ie, dealbata, dilatata, illudens, nebulens). Most Inocybe species also contain muscarine and may result in muscarinelike symptoms. Additionally, some Amanita species (ie, A muscaria, A gemmata, A pantherina, A parcivolvata) and some Boletus species contain muscarine, along with other toxins.
• Coprine poisoning is commonly due to ingestion of Coprinus mushrooms, including C atramentarius (inky cap), Coprine comatus, Coprine insignis, and Coprine micacius. Clitocybe clavipes may also contain coprine and cause a disulfiramlike reaction if ingested with alcohol.
• Immunoallergic reactions resulting in hemolysis, hemoglobinuria, and immune-complex mediated renal failure have occurred after the ingestion of P involutus.
• A large number of mushrooms cause GI symptoms when ingested by humans. These include species of most of the "little brown mushrooms," ie, from the genera Agaricus, Entoloma, Gomphus, Hebeloma, Lactarius, Lepiota, Lycoperdon, Pholiota, Polyporus, Ramaria, Russula, and Tricholoma. Additionally Chlorophyllum species (ie, esculentum, molybdates), Clitocybe nebularis, Laetarius species, P involutus, and many Amanita species cause GI irritation only. In Europe, P involutus has been reported to cause severe illness and death due to a Paxillus syndrome, which is characterized by abdominal cramps, diaphoresis, icy cold extremities, weakness, loss of consciousness, and circulatory collapse.
• Allergic bronchoalveolar syndrome results from the inhalation of spores of many Lycoperdon (puffball) species.
• Rhabdomyolysis with renal failure has been reported after the ingestion of Tricholoma species in France and Russula subnigricans in Taiwan.

Differential Diagnoses

Workup

Laboratory Studies

• Arterial blood gas analysis may demonstrate hypoxia and acidosis.
• Glucose: Hypoglycemia may develop suddenly during the gastroenteritis phase of gyromitrin poisoning, as well as during the hepatic failure phase of both gyromitrin and amatoxin poisoning. Hypoglycemia in the setting of liver failure signals a grim prognosis.
• Electrolytes: Electrolyte disturbances, such as hypokalemia, may occur in patients with severe gastroenteritis. Hypocalcemia may occur with orellanine-induced renal failure and in both gyromitrin and amatoxin poisoning. Hypophosphatemia may occur with amatoxin and gyromitrin poisoning, especially in children.
• Renal function tests: Blood urea nitrogen, creatinine level, and urinalysis are used as screening tools for renal function. Renal insufficiency occurs as a result of circulatory collapse from any cause, and, in the setting of amatoxin and gyromitrin toxicity, it may be part of the hepatorenal syndrome. A serum creatinine level greater than 1.4 mg/dL in the setting of amatoxin-induced hepatic failure is associated with a fatal course. Orellanine is a direct nephrotoxin and may induce oliguric renal failure several days or weeks after ingestion of the toxic mushroom. Mild renal insufficiency also may be observed with intravenous injection of psilocybin.
• Liver function tests: Hepatic failure is a common complication in amatoxin and gyromitrin ingestions. Biomarkers of hepatocellular necrosis include aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactic dehydrogenase. With amatoxin- and gyromitrin-induced hepatic necrosis, these biomarkers begin to rise exponentially 36-72 hours after the ingestion of these mushrooms. Severe hyperbilirubinemia also occurs, as do the prothrombin and activated partial thromboplastin time. An elevated ammonia heralds hepatic encephalopathy, and a bilirubin level exceeding 4.6 mg/dL is associated with a lethal course.
• CBC count: Anemia may be secondary to acute blood loss, which may complicate hemorrhagic gastroenteritis or may be secondary to hemolysis observed with gyromitrin poisoning. Anemia may also be secondary to renal failure observed in orellanine poisoning.
• Methemoglobin: Methemoglobinemia may be observed with gyromitrin poisoning and occasionally after an intravenous injection of psilocybin.
• Creatinine phosphokinase (CPK): Elevated CPK levels are a manifestation of rhabdomyolysis, which may be noted with Tricholoma and Russula species.
• Toxicology laboratory: Acetaminophen levels should be obtained for all patients with an unknown ingestion and should be suspected in all patients with fulminant hepatic failure. Toxicology screening for barbiturates, benzodiazepines, opiates, and alcohol should be obtained to help differentiate the cause of coma. Toxicology screening for phencyclidine, LSD, and cocaine may help differentiate the cause of hallucinations and agitation. Toxicology screening for phenothiazines may help differentiate the cause of hepatic failure or anticholinergic toxicity.
• Enzyme-linked immunosorbent assay (ELISA): ELISA analysis of urinary Amanitin appears efficacious in diagnosing amatoxin poisoning.
• Chromatography–mass spectrometry have been used to identify monomethyhydrazines (gyromitrin mushrooms), phenyethyleneamine (Psilocybe mushrooms), and orellanine (Cortinarius mushrooms).
• Hemagglutination inhibition has been used to detect anti-Paxillus immunoglobulin G (IgG).

Imaging Studies

• Radiography: Bilateral reticulonodular infiltrates may be seen with puffball-induced allergic bronchoalveolitis. A chest radiograph may reveal aspiration pneumonia or pulmonary edema. A CT scan of the brain is indicated in all patients with encephalopathy in order to rule out structural disease.
• Sonography: Renal ultrasound may show enlarged kidneys in orellanine poisoning.

Other Tests

• Electrocardiography: An electrocardiogram may reveal signs of hyperkalemia, which may complicate orellanine-induced renal failure.
• Mushroom toxicology
  • The most reliable method of identifying the mushroom involved in poisoning remains botanical identification of the fungus that was ingested. When no sample of the mushroom is available, postingestion analyses may be performed, but these are time consuming, and, by the time the results are available, the patient has recovered. The toxin may be recovered from the cooking water, gastric contents, blood, and urine of the poisoned patient.
  • Meixner test: When the mushroom specimen is available, the Meixner test provides a rapid method of identifying amatoxins. False-positive results may occur with psilocybin. The test consists of expressing a drop of mushroom juice onto a lignin paper (newspaper) and allowing it to air dry. A drop of hydrochloric acid (10-12 N) then is placed on the same spot, and the area is observed for any color change. The presence of amatoxin is suggested by a bluish discoloration of the area.

Procedures

• Liver biopsy
  • Gyromitrin toxicity - Diffuse hepatocellular damage
  • Amatoxin toxicity - Fatty degeneration of the liver, with extensive central zone necrosis and centrilobular hemorrhage
• Renal biopsy
  • Gyromitrin - Interstitial nephritis
  • Orellanine - Binds to tubular cells and may be detected as long as 6 months after ingestion
  • Renal biopsy reveals acute tubular necrosis and dedifferentiation of the proximal tubule. Electron microscopy reveals vacuolization of the tubular cells with loss of the brush border.

Histologic Findings

• Histologic examination of the liver reveals diffuse hepatocellular damage with gyromitrin toxicity and fatty degeneration of the liver with extensive central zone necrosis and centrilobular hemorrhage in amatoxin poisoning.
• Electron microscopy reveals changes consistent with extensive lipid peroxidation of the cytoplasm as well as the nucleus, vacuolization of the mitochondria, and clumping of the nucleolar chromatin.
• Renal biopsy findings may reveal interstitial nephritis in gyromitrin toxicity, acute tubular necrosis, and dedifferentiation of the proximal tubule in orellanine toxicity.
• Electron microscopy reveals vacuolization of the tubular cells with loss of the brush border.

Treatment

Medical Care

In the absence of a definitive identification of the mushroom, all ingestions should be considered serious and possibly lethal. Once diagnosed, treatment of mushroom poisoning is largely supportive.

Endotracheal intubation is recommended in all patients at risk of aspiration, and mechanical ventilation should be initiated in all patients with hypoxia, hypercarbia, acidemia, and shock. Aggressive rehydration in the ICU may be necessary in patients with choleralike gastroenteritis, and infusions of large amounts of electrolytes with dextrose solutions may be necessary to maintain vital functions.

Blood transfusions may be required in patients with hemorrhagic diarrhea, blood loss, and severe hemolytic anemia.

Blood pressure support with dopamine and norepinephrine may be required when crystalloids and colloid infusions fail. Hypoglycemia is treated with infusions of 10% dextrose with thiamine.

Cerebral edema is also treated in a conventional manner, which is aimed at reducing intracerebral pressure and preventing herniation. Hyperventilation, fluid restriction, osmotic diuresis, positioning the head of the bed at 30° from the horizontal plane, barbiturate coma, and anticonvulsants may be necessary.

GI decontamination, including whole-bowel irrigation, may be necessary. Beyond the first postprandial hour, orogastric lavage is not recommended because of the procedure's questionable efficacy. Activated charcoal plays a much more important role in limiting absorption of most toxins and is indicated for all patients with mushroom poisoning, regardless of the timing of presentation. When amatoxins are suspected, repeated doses of activated charcoal should be administered for 3-4 days to interrupt enterohepatic circulation of these toxins.

Once absorbed, the toxin may be neutralized with inhibition of the tissue uptake of the toxin, inhibition of the metabolic pathways involved in the development of toxicity, or enhanced elimination of the toxin. Specific therapy depends on the presumed toxin ingested.

Other complications of mushroom poisoning are treated in a standard manner.

Methemoglobinemia, which may occur after the ingestion of gyromitrins and, occasionally, after an intravenous injection of psilocybin, is treated with intravenous methylene blue.

Hemolysis, which may occur with gyromitrin toxicity, is usually mild, requires the administration of large amounts of intravenous fluids only to prevent renal complications, and rarely requires blood transfusions. Hemolysis due to Paxillus species may be more severe and may result in acute renal failure.

Agitation, commonly observed with hallucinogenic mushrooms, is treated with benzodiazepines. Phenothiazines are best avoided in this setting. Other causes of agitation (eg, hypoxia, hypovolemia, shock) should also be sought and corrected.

Anticholinergic poisoning may be treated with benzodiazepines and rarely requires physostigmine.

Severe muscarinic symptoms may require the infusion of small doses of atropine.

Patients with severe poisoning from disulfiram-containing mushrooms may benefit from fomepizole (4-methylpyrazole), which blocks alcohol dehydrogenase and, hence, the formation of the toxic aldehyde.

Renal failure, commonly observed with orellanine poisoning, may require hemodialysis. Patients with orellanine and orelline poisoning may benefit from hemoperfusion when it is performed within a week of ingestion, prior to the development of renal failure. Acute renal failure may also follow the ingestion of Amanita smithiamna and A proxima. Conventional indications for dialysis include uremic encephalopathy, fluid overload (with pulmonary edema), severe hyperkalemia, and acidosis. Patients with unremitting renal failure are candidates for renal transplantation.

Fulminant hepatic failure is a common complication observed with amatoxin and gyromitrin poisoning, and it should be treated aggressively because it commonly follows a fatal course.

The development of hepatic encephalopathy, hyperbilirubinemia greater than 4.6 mg/dL, prolongation of the prothrombin time to greater than twice the reference range, and a serum creatinine level greater than 1.4 mg/dL signal a fatal course. For these patients, orthotopic liver transplantation may be the only life-saving therapy. Therefore, transfer to a liver transplant center should be undertaken early in the setting of amanita poisoning and prior to the development of stage III encephalopathy, jaundice, or renal failure. Patients who develop shock, acidosis, hypoglycemia, and coagulopathy with hemorrhage and those who exhibit marked elevations of liver transaminases also should be considered for immediate orthotopic liver transplantation, even in the absence of hepatic encephalopathy, azotemia, and hyperbilirubinemia.

While waiting for an orthotopic liver transplant, patients with fulminant hepatic failure should be intubated early in order to prevent the added burden of aspiration pneumonia and hypoxia. Hypovolemia is treated with crystalloids. Hemorrhage is treated with blood transfusions and, when accompanied by coagulopathy, infusions of fresh frozen plasma. Lactulose may be administered to patients who exhibit hepatic encephalopathy. 

The development of renal failure in patients with fulminant hepatic failure warrants an attentive search for the etiology of the renal failure. Patients with hepatorenal syndrome are candidates for liver transplantation. Prerenal azotemia may be treated with cautious infusions of crystalloids, albumin, and fresh frozen plasma. Low-dose dopamine occasionally may aid in reversing renal failure. Should hemodialysis be required, continuous renal replacement therapy (CRRT) is the dialysis mode of choice because standard hemodialysis can cause rapid elevations in intracranial pressure and decreased cerebral perfusion.

Specific therapies include the following:

• Amatoxin  
• In addition to intensive airway and fluid therapy, correction of coagulation factors, multiple dose activated charcoal, a number of therapeutic options have been proposed, but to date, no controlled studies comparing the efficacy of different modalities have been published.
• The most frequently recommended therapy for amatoxin poisoning is intravenous benzyl penicillin, combined with silibinin (an extract of milk thistle) and cimetidine. N -acetylcysteine (NAC) has also been frequently recommended. Benzyl penicillin and silibinin appear to reduce the uptake of amatoxin by hepatocytes. Of the 2 modalities, silibinin has been purported to offer a better survival advantage compared to benzyl penicillin.
• Cimetidine (a cytochrome P-450 inhibitor) is used to inhibit the uptake of amatoxins by the mixed function oxidase system, thereby reducing toxicity. N -acetylcysteine, a glutathione precursor, capable of binding amatoxin-related free radicals, has been found in one case series to be efficacious.
• In a murine model, however, none of the proposed antidotal therapies were found to significantly affect the hepatic aminotransferase levels compared with controls; nor did any of them demonstrate an important decrease in hepatic necrosis histologically.⁴
• The intravenous form of silibinin is not currently available in the United States; however, an oral form (ie, silymarin) may be obtained. Silymarin is a dietary supplement found in health food stores.
• Corticosteroids, vitamin C, kutkin, aucubin, and thioctic acid have been used in the past but have no proven benefit and are no longer recommended. Charcoal hemoperfusion and hemodialysis are also ineffective in removing toxins because, once formed, the toxin is excreted rapidly by the kidneys.
• Plasma exchange transfusions have also been used with some success, but controlled studies are lacking. MARS (Molecular Absorbent Regenerating System), a new extracorporeal liver-assistance method that uses an albumin dialysate for the removal of albumin-bound toxins, has shown promising survival results in amatoxin-related hepatic failure. Hyperbaric oxygen therapy has been advocated for amatoxin poisoning and should be considered, when available.
• In the case of gyromitrin poisoning, in which systemic toxicity results from reduced concentrations of GABA, seizures may be overcome by the infusions of pyridoxine if they do not respond to benzodiazepines. Phenobarbital increases the metabolism of hydrazines to toxic compounds and should be avoided in the treatment of seizures in this setting. Hydrazines also inhibit the transformation of folic acid to tetrahydrofolic acid. Therefore, patients with gyromitrin toxicity should receive folinic acid.

Surgical Care

• Indications for immediate orthotopic liver transplant include the following:
  • Stage III hepatic encephalopathy
  • Serum bilirubin levels greater than 4.6 mg/dL
  • Prothrombin time prolongation greater than twice the reference range and unresponsive to fresh frozen plasma infusions (Patients with a prothrombin time >100 s should be considered for transplant.)
  • Quick-test value less than 20%
  • Other suggested indications include age younger than 12 years, serum creatinine level greater than 1.4 mg/dL, hemorrhage, shock, acidosis, hypoglycemia, and factor V deficiency (concentration <10% of the reference range).

Consultations

• Identification of the mushroom: Specialists from the regional poison center, toxicologists, botanists, and mycologists may assist in the identification of the mushroom. The Internet may also provide answers. However, decontamination and treatment should not await the identification of the mushroom.
• Transplant surgery: Consultation is indicated as soon as the diagnosis of amanita-induced fulminant hepatic liver failure is entertained.
• Nephrology: Consultation is indicated for renal failure or when dialysis or hemoperfusion is required.

Diet

• Hepatic failure: The catabolic rate of patients with fulminant hepatic failure (FHF) is quadruple the reference range catabolic rate, and patients in FHF should receive adequate protein and carbohydrates so that hepatocyte regeneration may be optimized. Limiting protein in patients with FHF is associated with an increased mortality rate. Patients with acute FHF also are at risk for hypoglycemia and require close monitoring of their glucose levels along with infusions of 10% dextrose solutions. Patients receiving high-carbohydrate solutions also must receive thiamine.
• Renal failure: Use of essential amino acids is not associated with better outcomes than is the use of standard amino acids. Nutrition of patients with acute renal failure should include amino acids and glucose, with a relatively normal calorie-to-nitrogen ratio.

Medication

The goals of pharmacotherapy are to neutralize the toxin, to reduce morbidity, and to prevent complications.

Anticonvulsants

These agents prevent seizure recurrence and terminate clinical and electrical seizure activity.

Lorazepam (Ativan)

Sedative hypnotic with short onset of effects and relatively long half-life.
By increasing the action of gamma-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter in the brain, it may depress all levels of CNS, including limbic and reticular formation.
Monitor patient's blood pressure after administering dose. Adjust as necessary.

Dosing

Adult

2 mg/dose IV slowly over 2-5 min; not to exceed 8 mg/dose

Pediatric

0.05-0.1 mg/kg IV slowly over 2-5 min; not to exceed 2 mg/dose

Interactions

Toxicity of benzodiazepines in CNS increases when used concurrently with alcohol, phenothiazines, barbiturates, MAOIs, narcotics, valproate, oral contraceptives, and antihistamines

Contraindications

Documented hypersensitivity; preexisting CNS depression; hypotension; narrow-angle glaucoma

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in renal or hepatic impairment, myasthenia gravis, organic brain syndrome, respiratory depression, or Parkinson disease

Diazepam (Valium)

Depresses all levels of CNS (eg, limbic, reticular formation), possibly by increasing activity of GABA.

Dosing

Adult

5-10 mg IV q10-15min; not to exceed 30 mg/8h period

Pediatric

0.05-0.3 mg/kg IV q10-15min; not to exceed 5 mg/dose

Interactions

Effects potentiated with alcohol, barbiturates, MAOIs, narcotics, valproate, oral contraceptives, and antihistamines

Contraindications

Documented hypersensitivity; narrow-angle glaucoma

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution with other CNS depressants, low albumin levels, hepatic disease (may increase toxicity), impaired renal function, and respiratory depression

Phenobarbital (Barbita, Luminal)

Interferes with transmission of impulses from thalamus to cortex of brain.

Dosing

Adult

Loading dose: 15-20 mg/kg IV at 25-50 mg/min
Maintenance dose: 1-5 mg/kg/d

Pediatric

Administer as in adults

Interactions

May decrease effects of chloramphenicol, digitoxin, corticosteroids, carbamazepine, theophylline, verapamil, metronidazole, and anticoagulants (patients stabilized on anticoagulants may require dosage adjustments if added to or withdrawn from their regimen); coadministration with alcohol may produce additive CNS effects and death; chloramphenicol, valproic acid, and MAOIs may increase phenobarbital toxicity; rifampin may decrease phenobarbital effects; induction of microsomal enzymes may result in decreased effects of oral contraceptives in women (must use additional contraceptive methods to prevent unwanted pregnancy; menstrual irregularities also may occur)

Contraindications

Documented hypersensitivity; severe respiratory disease; marked impairment of liver function; nephritis

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

In prolonged therapy, evaluate hematopoietic, renal, hepatic, and other organ systems; caution in fever, hyperthyroidism, diabetes mellitus, and severe anemia because adverse reactions can occur; caution in myasthenia gravis and myxedema

Antiemetics

These agents block the dopamine receptors in the chemoreceptor trigger zone.

Prochlorperazine (Compazine)

May relieve nausea and vomiting by blocking postsynaptic mesolimbic dopamine receptors through anticholinergic effects and depressing reticular activating system.
Not recommended in children <20 lb due to high incidence of extrapyramidal effects.

Dosing

Adult

5-10 mg IV slowly; not to exceed 40 mg/d

Pediatric

Not established

Interactions

Coadministration with other CNS depressants or anticonvulsants may cause additive effects; administration with epinephrine may cause hypotension; cardiovascular effects are potentiated with use of diuretics

Contraindications

Documented hypersensitivity; bone marrow suppression; narrow-angle glaucoma; severe liver or cardiac disease

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Drug-induced parkinsonian syndrome or pseudoparkinsonism occurs quite frequently; akathisia is the most common extrapyramidal reaction in elderly patients; lowers seizure threshold; caution in patients with history of seizures; caution in cardiovascular disease (may cause arrhythmias and hypotension)

Metoclopramide (Reglan)

Works as antiemetic by blocking dopamine receptors in the chemoreceptor trigger zone of the CNS.

Dosing

Adult

10 mg IV slowly up to 1 mg/kg

Pediatric

2.5 mg IV slowly up to 1-2 mg/kg IV q2-4h

Interactions

Anticholinergic agents may antagonize effects of metoclopramide; opiate analgesics may increase metoclopramide toxicity in CNS

Contraindications

Documented hypersensitivity; pheochromocytoma; Parkinson disease; GI obstruction; GI bleed

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in history of mental illness and Parkinson disease; may induce seizures, changes in mental status, extrapyramidal symptoms, and arrhythmias

GI decontaminants

These agents are empirically used to minimize systemic absorption of the toxin.

Activated charcoal (Liqui-Char)

Emergency treatment in poisoning caused by drugs and chemicals. Network of pores present in activated charcoal absorbs 100-1000 mg of drug per g of charcoal. Does not dissolve in water. For maximum effect, administer within 30 min after ingesting poison. The first dose of activated charcoal generally is used with a cathartic (eg, sorbitol 1 g/kg PO). Additional doses of sorbitol are not administered to children due to resultant excessive intraintestinal osmotic shifts, electrolyte imbalance, and intravascular volume depletion.

Dosing

Adult

1-2 g/kg PO; repeat q4h

Pediatric

<1 year: 1 g/kg PO, without sorbitol
1-12 years: 1-2 g/kg PO; repeat q4h; use sorbitol for only 1-2 doses
>12 years: Administer as in adults

Interactions

May inactivate syrup of ipecac if used concomitantly; effectiveness of other medications decrease with coadministration; do not mix charcoal with sherbet, milk, or ice cream (decreases absorptive properties of activated charcoal)

Contraindications

Documented hypersensitivity; poisoning or overdosage of mineral acids and alkalies

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May result in intestinal obstruction; aspiration may result in tracheal obstruction and bronchiolitis obliterans; combination with a cathartic in children may result in hemodynamic instability; not very effective in poisonings of ethanol, methanol, and iron salts; induce emesis before administering activated charcoal; after emesis with ipecac, 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

Polyethylene glycol (GoLYTELY)

Laxative with strong electrolyte and osmotic effects that has cathartic actions in GI tract.

Dosing

Adult

1-2 L/h PO until rectal effluent is clear

Pediatric

50-250 mL/kg/h PO until rectal effluent is clear

Interactions

Reduces effectiveness and absorption of oral medications

Contraindications

Documented hypersensitivity; colitis; megacolon; bowel perforation; gastric retention; GI obstruction

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in ulcerative colitis and hot loop polypectomy

Antidotes

Most amatoxin antidotes are experimental and based on animal studies and/or anecdotal reports of success in humans.

Penicillin G (Pfizerpen)

Interferes with synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms. Blocks amanitin uptake by hepatocytes and prevents amanitin from binding to RNA polymerase.

Dosing

Adult

1 million U/kg/d IV

Pediatric

<15 kilograms: 600,000 U IV
15-30 kilograms: 1 million U IV

Interactions

Probenecid can increase effects of penicillin; coadministration of tetracyclines can decrease effects of penicillin

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in impaired renal function; high doses are associated with seizures

Silibinin (Silibinin Plus)

Compound made of silymarin, an extract of the milk thistle plant Silybum marianum. May act as a free radical scavenger or may interrupt enterohepatic circulation. Blocks amanitin uptake by hepatocytes. Available in Europe but not the United States.

Dosing

Adult

Intravenous loading: 5 mg/kg over 1 h, followed by continuous IV infusion of 20/mg/kg for 3 d

Pediatric

Not established

Interactions

Decreased efficacy when activated charcoal is administered concomitantly; may decrease effectiveness of oral contraceptives

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

None reported

N-acetylcysteine (Mucosil, Mucomyst)

May provide substrate for conjugation with toxic metabolite.

Dosing

Adult

Loading dose: 140 mg/kg PO
Maintenance dose: 70 mg/kg PO q4h

Pediatric

Administer as in adults

Interactions

Absorption is reduced by charcoal

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

GI distress may occur

Pyridoxine (Nestrex)

May be used in conjunction with benzodiazepines for the treatment of convulsions that develop with gyromitrin toxicity. Involved in synthesis of GABA within the CNS.

Dosing

Adult

25 mg/kg up to 5 g IV over 30 min

Pediatric

Administer as in adults

Interactions

Pyridoxine may decrease levodopa, phenytoin, and phenobarbital serum levels

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Doses >70 mg/kg are associated with increased toxicity; long-term use of high doses of pyridoxine may result in neuropathy manifested by numbness, paresthesias, or unsteady gait

Methylene blue (Urolene Blue)

In reduced form, leukomethylene blue is an electron donor to reduce methemoglobin. Reduction of methylene blue is by NADPH generated by G-6-PD.

Dosing

Adult

1-2 mg/kg IV over 5 min

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity; renal insufficiency

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

In G-6-PD deficiency, can cause profound anemia; do not inject into CNS

Fomepizole (Antizol)

Anticortinarius antidote with better safety profile than ethanol. Easier to dose and administer. In contrast to ethanol, 4-MP levels do not need to be monitored during therapy.

Dosing

Adult

15 mg/kg IV over 30 min, then 10 mg/kg q12h for 4 doses

Pediatric

Not established

Interactions

Inhibitory effects on alcohol dehydrogenase are increased in presence of ethanol

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Do not administer as bolus; caution in breastfeeding women because no information on excretion of this medication in breast milk is available; caution in renal impairment; may induce seizures

Follow-up

Further Inpatient Care

• Amatoxin poisoning: Further inpatient care of patients who survive focuses on the management of direct complications of poisoning and on the management of the liver transplant.
• Gyromitrin poisoning: Further inpatient care of patients who survive focuses on the management of complications of poisoning, such as rhabdomyolysis, methemoglobinemia, and hemolysis, and on management of the liver transplant.
• Orellanine poisoning: Further inpatient care of patients focuses on the management of complications such as renal failure.

Transfer

Transfer to a liver transplant facility should occur early in the course of FHF and prior to the development of stage III hepatic encephalopathy.

Deterrence/Prevention

Education regarding the poisonous nature of wild mushrooms may act as a deterrent to mushroom foraging and ingestion.

Complications

• Respiratory complications: Aspiration pneumonia common to all poisonings involves loss of airway protective reflexes. Noncardiogenic pulmonary edema may complicate poisonings.
• CNS complications: Convulsions are common in gyromitrin poisoning, but they also may be due to hypoxia, acidosis, and metabolic abnormalities. Cerebral edema may be a complication of hypoxia, acidosis, trauma, and hepatic failure.
• Hepatic complications: Fulminant hepatic failure (FHF) is a complication for amatoxin and gyromitrin poisoning.
• Renal failure is a common complication of orellanine poisoning but also may be due to hypoperfusion and shock and may be part of the hepatorenal syndrome.
• Methemoglobinemia may complicate gyromitrin poisoning.
• Hemolysis may complicate gyromitrin poisoning.
• Hypoglycemia is a common complication of hepatic failure caused by poisoning with gyromitrins and amatoxins.
• Trauma may complicate hallucinogenic mushroom poisoning.
• Hypovolemia and electrolyte disturbances may complicate any mushroom poisoning.

Prognosis

• Amatoxin poisoning: With good supportive care, the mortality rate for amatoxin poisoning may be reduced from 60% to less than 10%.  In a retrospective analysis of amatoxin poisoned patients, Giannini found found that the evolution of hepatic transaminases and prothrombin time over the initial 4 days were highly predictive of recovery or death.⁵
• Gyromitrin poisoning: Most patients recover; death is rare in the United States, but, in some areas of Europe, mushrooms containing gyromitrins account for the most mushroom fatalities.
• Orellanine poisoning: Although it is not found in the United States, in some areas of Europe, mushrooms containing orellanine account for the most mushroom fatalities. A shorter time course between ingestion and toxicity portends a worse prognosis. Mild renal insufficiency may resolve a few months after the ingestion.
• Psilocybin poisoning: Prognosis is excellent; no fatalities were reported in the United States in 2004.

Patient Education

• Education regarding the poisonous nature of wild mushrooms may act as a deterrent to mushroom foraging and ingestion.
• Patients ingesting coprine-containing mushrooms should be educated regarding the interaction with alcohol.
• For excellent patient education resources, visit eMedicine's Poisoning Center and Poisoning - First Aid and Emergency Center. Also, see eMedicine's patient education articles Poisoning and Activated Charcoal.

Miscellaneous

Medicolegal Pitfalls

• Failure to consider the diagnosis of mushroom poisoning
• Failure to recognize that more than one species of mushroom was ingested
• Failure to institute supportive therapy prior to the identification of the mushroom
• Failure to recognize and treat complications
• Failure to consider liver transplant, when indicated

Special Concerns

• Children are more susceptible to volume depletion and mushroom toxicity (mushroom poisoning) than are healthy adults.
• Elderly patients are more susceptible to volume depletion than are healthy adults.
• Patients with comorbidities have worse prognoses.

Multimedia

Media file 1: Amanita phalloides.

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Keywords

mushroom toxicity, mushroom poisoning, mycetism, toadstool poisoning, amatoxins, gyromitrins, orellanine, muscarine, psilocybin, muscimol/ibotenic acid, coprine, general GI irritants, neurotoxins, nephrotoxins, myotoxins, phallotoxins, virotoxins, destroying angel, autumn skullcap, Amanita phalloides, Amanita virosa, Amanita verna, Galerina autumnalis, false morel, Gyromitra esculenta, Gyromitra ambigua, Gyromitra gigas, Gyromitra infula, early false morel, Verpa bohemica, webcap, Cortinarius orellanus, Cortinarius speciosissimus, Cortinarius gentilis, Cortinarius callisteus, Cortinarius rainierensis, Cortinarius splendens, Amanita proxima, fly agaric, panthercap, Amanita muscaria, Amanita pantherine, Psilocybe, Panaeolus, Gymnopilus, Copelandia, Conocybe, Psathyrella Pluteus, sweater mushroom, Clitocybe dealbata, Paxillus involutus, green gill, Chlorophyllum molybdates, jack-o'-lantern, Omphalotus illudens, pepper bolete, Boletus piperatus, horse mushroom, Agaricus arvensis

Contributor Information and Disclosures

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Rania Habal, MD, Assistant Professor, Department of Emergency Medicine, New York Medical College
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