Mushroom Ingestion and Toxicity: Toxin Identification, Patient Assessment, and Administration of Life-Saving Antidotes
Mushroom Ingestion and Toxicity: Toxin Identification, Patient Assessment, and Administration of Life-Saving Antidotes
Author: Ginger W. Wilhelm, MD, FACEP, Assistant Professor of Emergency Medicine and Residency Director, University of Texas—Houston Department of Emergency Medicine.
Peer reviewer: Jeffrey S. Jones, MD, Associate Professor and Research Director, Spectrum Health/Michigan State University Program in Emergency Medicine, Grand Rapids, MI.
Proper medical care of a patient who has ingested a wild mushroom that may be toxic can seem like a daunting task for the emergency physician. Many issues must be considered depending upon the patient’s age, site of contamination, and presenting symptoms. For example, is gastric decontamination warranted for the toddler who took a bite of the little brown mushroom ("LBM") found on the lawn? What is a logical approach to the teenager who thought he ingested a hallucinogenic psilocybe mushroom, but who is instead stricken with profuse vomiting and diarrhea two hours later? What type of treatment and referral is warranted for the mushroom forager who presents with delayed hepatotoxicity following ingestion of freshly picked field mushrooms?
In this review of mushroom toxicity and poisoning, the authors provide a logical framework for approaching the patient with possible toxic mushroom ingestion. At the outset it should be stressed that in any given mushroom ingestion, the odds are in favor of a benign outcome unless the patient was intent upon suicide. Of the 5,000-10,000 species of mushrooms in North America, only about 100 are toxic, and only about 10 species are considered deadly.1,2 However, even the most feared of all, Amanita phalloides (the "death cap"), has been found growing in urban yards. As a result, in each case, an attempt should be made to identify the mushroom. Sources for identification will be presented in this review.
Prediction of patient outcome also can be based upon a symptoms approach. A symptom complex that is predictably associated with a toxin or group of toxins is known as a toxidrome. A good example of a toxidrome is the symptom complex associated with an organophosphate poisoning. Those symptoms of cholinergic nervous system excess, often given the acronym "SLUDGE," consist of salivation, lacrimation, urination, diarrhea, gastrointestinal distress, and emesis. One of the mushroom toxin groups that contains muscarine causes a very similar symptom complex.
The currently known mushroom toxins can be categorized into eight groups, each with a characteristic symptom complex. The most deadly Amanita species, with their potential for delayed hepatic failure, fall into the first group. The hallucinogenic psilocybe is an example of another. The last group contains the miscellaneous gastrointestinal irritants, which cause unpleasant symptoms, but usually have benign outcomes, particularly with appropriate fluid resuscitation. This review outlines the epidemiology of mushroom poisoning and highlights the "at risk" populations. Each toxin group is discussed with respect to pathophysiology and specific treatments.
Finally, a general approach to mushroom ingestions is provided, including questions that should be asked about each ingestion.
— The Editor
Epidemiology and Mushroom Identification
The American Association of Poison Control Centers (AAPCC) maintains a database of toxic exposures known as the Toxic Exposure Surveillance System (TESS). In 1998, of the 2.2 million reported human exposures to toxins, approximately 10,000 were mushroom exposures (0.5% of total exposures).3 This percentage has remained constant for several years.4 It is of interest to note that the number of ingestions of hallucinogenic mushrooms doubled between 1989 and 1998.4,5
Identification. Fortunately, the majority of mushroom exposures will have a benign outcome. However, many cases go unreported, so that the actual number of cases with a benign outcome may be considerably higher. Although a positive identification of the involved mushrooms is not made in the majority of cases, this should not deter the clinician from trying to make an identification in each case. Most exposures occur in children younger than 6 years, and they occur as a result of "backyard grazing" of LBM’s. However, deadly species of Amanita have been found in backyards, so any given ingestion should be considered potentially toxic, and an attempt should be made at definitive identification.
A mycologist can prove invaluable for identification of mushrooms. Accordingly, the emergency physician should know how to contact a mycologist in his or her area. These individuals usually are listed with the local Poison Control Center, or they may be contacted through the Rocky Mountain Poison Control and Drug Center (303-739-1123). Other sources include local universities, botanical organizations, museums, mycological societies, commercial growers, or the U.S. Department of Agriculture.5 If a mycologist is not available, field guidebooks, Certified Poison Centers, and the Poisondex database may be helpful for mushroom identification.6 A useful Internet site for contacting mycological societies in the United States and Canada is http://namyco.org (North American Mycological Association). A guide to mushroom databases also can be found at http://molbiol.soton.ac.uk/msdn/web.html.
Because mushroom identification can be complex, it is preferable to consult with experts. Mushroom identification keys can be helpful, but can be difficult to interpret.7 To use a key requires familiarity with mushrooms and their anatomy. Identification of a mushroom can be foiled if a component of the fungus, such as the annulus or volva (see Figure 1) has been removed from an Amanita specimen. Moreover, individual specimens in the same species may vary considerably in color, shape, and odor.
A sample mushroom of the type ingested should be retrieved if possible; even uneaten portions of a meal may prove helpful. Emesis and stool can also be saved for potential spore and chemical analysis. Uneaten mushroom specimens are best transported by courier to the mycologist in a dry paper bag, as transportation in plastic will hasten decomposition.8 There can be other pitfalls to correct mushroom identification. More than one type of mushroom may have been ingested, compromising the reliability of diagnosis according to symptom complex and onset of symptoms. Furthermore, bacterial contamination may be the cause of gastrointestinal symptoms. A few individuals may experience idiosyncratic or allergic symptoms instead of true toxin ingestion.
Epidemiology and Ingestion Patterns. A mushroom is actually the fruiting body of a much larger organism, the mycelium, which is underground. The mushroom fruiting bodies often emerge from the mycelium, yielding the "fairy rings" of legend and folklore. Because fungi have no chlorophyll, they must extract nutrients from other sources; as a result, they live in symbiosis with trees or are found on cow dung. Mushrooms change shape as they emerge from the ground, starting as egg shaped inside a veil, and then maturing with fully extended umbrella-like cap with the spores underneath. Some species have remnants of the veil remaining as "warts" on top.9 (See Figure 1.)
Both recreational and commercial mushroom hunting have increased in the last few years.10 In the Pacific Northwest, mushroom hunting has been nicknamed "a new gold rush," and exportation of mushrooms such as the matsutake or "pine mushroom" to Japan (where supplies have diminished) has become a multimillion-dollar industry. Amanita smithiana, which has been associated with renal failure, has been mistaken for the matsutake by amateurs.12,13 The highly prized chanterelle can be confused with the American Jack O’ Lantern, which is toxic. Because mushrooming is more common in Europe, several hundred deaths are reported annually from this part of the world.10 Immigrants from Asia and Europe are considered potential "at risk" populations for making errors with mushroom identification. However, no ethnic group should be excluded as "at risk" because mushrooms have always been a food source, especially during times of war and in periods of deprivation.14
In a case report from 1989, a group of four illegal aliens who had been without food for several days were fatally poisoned after consuming Amanita phalloides picked in a field in southern California. It is notable that they did not seek medical care until about three days after the ingestion.15 A 1996 study of patients with serious mushroom poisonings who were hospitalized in California showed that poisoning rates between ethnic groups did not vary significantly. This report also mentioned another death, in a migrant farm worker, which also appeared to be linked to Amanita ingestion. The authors noted that their study might have been limited by the fact that not all groups presented themselves for medical care. They also concluded that children younger than age 5 had a higher rate of hospitalization than other age groups.10
Mushroom Toxin Classification System
Mushroom toxins have been classified into several groups. Unfortunately, different authorities use slightly different classification systems. This review uses the classification system outlined by the Poisondex database by Micromedex and the Handbook of Mushroom Poisoning, edited by Spoerke and Rumack.6,7 Mushroom toxins generally fall into one of eight groups, as listed below:
I. Cyclopeptide-containing group (e.g., Amanita phalloides)
IA. Cyclopeptides/Orellanine (Cortinarius mushrooms)
II. Muscimol/Ibotenic Acid-containing group
III. Gyromitrin-containing group (monomethylhydrazine)
IV. Muscarine-containing group
V. Coprine-containing group
VI. Psilocybin-containing group
VII. Miscellaneous/gastrointestinal irritants
A few exceptions to the aforementioned classification systems do occur, and it is likely that more will be discovered as knowledge of the chemistry of mushroom toxins expands. For example, in the Pacific Northwest there have been recent case reports of acute renal failure associated with ingestion of Amanita smithiana as mentioned above. However, the toxidrome of renal failure is more typically associated with Cortinarius mushrooms, rather than with members of the Amanita genus. The implicated toxins, pentynoic acid and allenic norleucine, are distinct from both groups I and IA.13 Please refer to Table 1, which provides an overview of mushroom toxins, their associated symptoms, and treatment strategies.
| Table 1. Mushroom Toxins, Symptoms, and Treatment Strategies | |||
| Toxin | Onset & Symptoms | Treatment | Prognosis |
| I. Cyclopeptides | First 6-10 hours: gastrointestinal symptoms, followed by silent phase; In 2-3 days, delayed hepatic failure, hypoglycemia, pancreatitis |
Admission to the ICU, fluids, activated charcoal, high-dose penicillin-G, silibinin, cimetidine, liver transplant |
20-30% mortality |
| Ia. Orellanine | Delay of days to weeks, at which point renal failure is the predominant symptom |
Hemodialysis, renal transplant | Mortality rare with dialysis |
| II. Muscimol/Ibotenic acid |
30-90 minutes of intoxication, agitation, hallucinations, seizures |
Supportive treatment, benzodiazepines |
Full recovery |
| III. Monomethylhydrazine | Delay of 6-24 hrs, gastrointestinal then CNS, seizures, liver, RBCs. | Supportive, benzodiazepines, pyridoxine 25 mg/kg |
Mortality 15-35% |
| IV. Muscarine | < 2 hr onset gastrointestinal and cholinergic excess: perspiration, lacrimation, salivation |
Atropine and fluids | Full recovery |
| V. Coprine | < 1 hr after ethanol ingestion, if ethanol taken within 72 hrs of mushroom. Disulfiram- like with headache, flushing, tachycardia, vomiting, potension |
Fluids, vasopressors | Full recovery |
| VI. Psilocybin | < 1 hr of euphoria, hallucinations | Reassurance, calm environment, benzodiazepines |
Full recovery |
| VII. Miscellaneous gastrointestinal irritants |
< 2 hr onset of gastrointestinal symptoms | Charcoal, fluids | Full recovery |
| Adapted from: Goldfrank LR, Flomenbaum NE, Lewis NA, eds. Goldfrank's Toxicologic Emergencies. 6th ed. Stamford, Conn: Appleton & Lange; 1998:1209; and Schneider SM, Cochran KW, Krenzlok EP. Mushroom poisoning: Recognition and management. Emerg Med Reports 1991;12:83. |
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Cyclopeptide-Containing Mushrooms
Although exposures to cyclopeptide-containing mushrooms are uncommon, they account for 95% of all mushroom fatalities in North America and a significant percentage of mushroom-related deaths in Europe.8,16,17 In this regard, the Amanita genus is associated with the greatest number of fatalities, and three of the most common species are A. phalloides (the "death cap"), A. verna, and A. virosa (the "destroying angel"). However, not all members of the genus Amanita contain the highly toxic cyclopeptide toxins; some are associated with other toxidromes (see group II below) and others are listed in some field guides as edible.18
Moreover, the toxic cyclopeptides have been reported in other genera, including selected species of Galerina and Lepiota genera. Interestingly, cyclopeptide-containing mushrooms exist on all continents except Antarctica. Amanita phalloides is known to be indigenous to the gulf coastal regions of the United States, and Amanita species have been found throughout the United States including urban yards, although they are more commonly found in temperate forests, especially in symbiosis with oak trees.19
In addition to the cap and stem, members of the Amanita group usually have both an annulus (ring) around the stem and a cup (volva) at the base.19,20 (See Figure 1.) It is important to remember that these distinguishing features for identifying an Amanita mushroom might be separated from an individual specimen. A typical A. phalloides has no warts on the cap, is light to olive green or brown, but also can be off-white. It has white gills on the undersurface on the cap and white spores (spore color must be determined by spore print).18,20 A single death cap contains enough toxins to be fatal to an adult.18,19
Clinical Syndrome. The offending toxins are small cyclopeptides, among them amatoxins, phallotoxins, and virotoxins.8 Phalloidins or phallotoxins impair cell membrane function, but have limited gastrointestinal (GI) absorption, so it is postulated that the phalloidin’s toxicity is primarily gastrointestinal in nature.16,21,22 The amatoxins are heat stable, and therefore, cooking does not diminish toxicity. Amatoxins are absorbed systemically and cause severe hepatic, renal, and central nervous system (CNS) damage.23 The cyclic structure of amatoxin resists digestive peptidases.24 Alpha-amanitin is cytotoxic because it interferes with RNA polymerase II, an enzyme required for protein synthesis.25 The liver and kidneys are primary target organs because of their high rate of protein synthesis.21 Toxins are eliminated in the urine and feces for several days following ingestion; they can be detected by various chemical analyses of serum, urine, gastrointestinal fluid, and liver and by kidney biopsy.8,19 Serum amatoxin levels do not correlate well with the severity of illness.19,21,26,27
The initial phase of a cyclopeptide poisoning is similar to several other mushroom toxicities and may be indistinguishable from gastroenteritis. Typically, there is a delay of 6-10 hours after ingestion before the onset of severe abdominal pain, vomiting, and cholera-like diarrhea.5,8,27 The stools may progress to contain blood and mucus. This phase usually lasts several hours, and if the patient is not identified as a potential amatoxin victim, he or she may be inadvertently discharged without adequate follow-up. The stages of toxicity that follow, which are somewhat analogous to acetaminophen toxicity, include a second quiescent phase in which the patient feels well but the liver enzymes begin to rise.
The second phase is followed by a third phase at 3-5 days post ingestion and is characterized by potentially severe hepatic, renal, and occasionally, pancreatic involvement.8,19 The patient may manifest fever, fatigue, malaise, loss of appetite, nausea, abdominal pain, dark urine, and jaundice.26 Lab abnormalities include elevated liver function tests, hyperbilirubinemia, abnormal clotting studies, hypoglycemia, hypocalcemia, and elevated creatinine, and blood urea nitrogen.5,8,16 Hepatic necrosis, which is primarily centrilobular, may rapidly progress to clinical hepatic failure and encephalopathy. Renal failure also may ensue by direct toxic effect or by the hepatorenal syndrome.25 Bone marrow suppression also has been noted.22 Death from fulminant hepatic failure typically occurs at an average of eight days post ingestion.19,22
Treatment. Current therapy has reduced mortality associated with A. phalloides ingestion from the 50-60% rate of previous years to 20-30%.8,19,22,25 Children, it should be noted, have a predictably higher mortality rate.8,22 Any patient in whom cyclopeptide ingestion is suspected should be admitted to the hospital. Initial management should include vigorous monitoring and replacement of expected fluid and electrolyte losses, which may be several liters per day.22 Emesis and lavage are usually not indicated because of the emesis induced by the toxin itself.8 Because amatoxin undergoes enterohepatic circulation, oral multidose activated charcoal is indicated.8,19 The initial dose is 30-100 grams of charcoal in 240 mL diluent orally, with repeat doses of 20-50 grams every 2-6 hours. For children, a dose of 1-2 gm/kg in 4 mL/kg diluent is recommended.19 A cathartic is ill-advised if the patient has diarrhea. The patient should be hemodynamically monitored and lab parameters also followed closely.
Other therapeutic approaches also are used. High-dose penicillin G in doses of 300,000 to 1,000,000 U/kg per day by intravenous infusion has been shown in experimental studies to inhibit liver uptake of amatoxin and is used in several centers.8,19,21,22,26 Another drug, Silibinin, available in Europe for parenteral use, is derived from the milk thistle plant and has fewer side effects than penicillin.27 The oral form, silymarin, is more available in the United States. Silibinin and silymarin are thought to work by a mechanism similar to that of high-dose penicillin.
High-dose cimetidine, a cytochrome P-450 inhibitor, is often used for its theoretical role in preventing toxic metabolites.5,19,28,29 Thioctic (alpha-lipoic) acid is another experimental therapy. It is an antioxidant that may be of benefit in some case series but is unproven.8,19 Some of the therapies listed above have become part of many centers’ standard treatment regimens, even though they have not been subjected to well controlled studies; consequently, their precise benefit may be difficult to determine.
If a patient begins to manifest significant hepatotoxicty, he or she should be transferred to a liver transplantation center. Indications for liver transplantation include markedly prolonged prothrombin time and other clotting abnormalities, hypoglycemia, acidosis, and hyperbilirubinemia.16,22,29 Generally, liver transplantation is advised before the onset of advancing hepatic encephalopathy because of the associated poorer prognosis once hepatic encephalopathy has been established.16,26 Recent case series report good results when liver transplantation is performed according to the aforementioned criteria.16,22,30
Orellanine- and Cortinarin-Containing Mushrooms
Orellanine and related compounds are found in some of the Cortinarius species of mushrooms. Cortinarius mushrooms are widespread in Europe and have been reported in North America, but ingestions of this genus are much more rare in the United States.3,29,31,32 Cortinarius orellanus is a large handsome mushroom with a vivid orange and brown cap that flourishes in late summer through fall.
The world literature’s first large case series was reported in the 1950s from Poland (where "mushrooming" is very common) by Gryzmala, who also did work to isolate the toxins.32 Orellanine has a bipyridyl structure similar to the deadly herbicide paraquat but has a different mode of action and exerts it principal effects on the kidneys.8,21,31,33 Poisonous Cortinarius species also have been reported to contain cyclopeptides that are closely related to the amatoxins. These are called cortinarins A, B, and C. Cortinarins A and B have been shown to be nephrotoxic in laboratory animals.24
Clinical Syndrome. The target organ of Cortinarius toxicity is the kidney. The delay of symptoms is one of the longest of all mushroom poisonings: from 3 to 20 days, with the more severe cases presenting closer to three days.34 Because of this delay in the onset of symptoms, the patient may not make the association between symptoms and the mushroom ingestion. In some cases, the diagnosis is often not made until renal failure has already started.33
The typical symptoms of Cortinarius or orellanine poisoning consist of severe thirst, headache, chills, polyuria or oliguria, and back pain.21,32,33 On laboratory examination, signs of renal failure are evident, including elevation of blood urea nitrogen and creatinine; the urinalysis may show hematuria, red cell casts, and proteinuria. Other lab parameters usually are normal, including liver enzymes.32
Treatment. Treatment of orellanine poisoning is supportive, with hemodialysis being indicated for cases with severe renal impairment. Approximately 50% of patients requiring hemodialysis will eventually recover renal function and will not require permanent dialysis or renal transplant.33 Extracorporeal hemoperfusion in combination with hemodialysis also has been suggested by some authors.21,32
Muscimol/Botenic Acid-Containing Mushrooms
Muscimol, and its derivative, ibotenic acid, are stereochemically related to gammaminobutyric acid (GABA) and glutamic acid, respectively. As a result, muscimol is a strong GABA agonist and has sedative properties; ibotenic acid is a CNS stimulant.8,21
These compounds are found in a few species of Amanita, but not in Amanita phalloides as they are group I toxins. Examples of muscimol/ibotenic acid-containing mushrooms include Amanita muscaria and A. Pantherina (the "panther" because it is brown with white spots).18 The toxidrome is sometimes known as the "pantherina syndrome." Amanita muscaria is a large, bright orange mushroom with white spots on the cap. Both types of mushrooms are distributed worldwide, and A. muscaria has the nickname "fly agaric" for its ability to attract and kill flies (agaric means mushroom).35 These mushrooms contain other chemicals in smaller amounts such as muscarine, which was isolated first from A. muscaria in 1869 and used in the elucidation of cholinergic receptors.
Clinical Syndrome. The CNS effects of the muscaria mushroom have been known for centuries. In the 16th century, Siberians would drink the urine of other people who had become intoxicated from eating the mushroom, with similar intoxicating effects; suggesting that the toxins are excreted at least partially unchanged in the urine.35
After ingestion of the mushroom, symptoms begin rapidly, usually within 30-90 minutes, and they are similar to ethanol intoxication.2,21,36 There is often a mixture of CNS depression and stimulation, causing drowsiness alternating with agitation, ataxia, and mild hallucinations. Occasionally, patients may become comatose or have seizures. Gastrointestinal symptoms usually are mild.
Treatment of the muscimol/ibotenic acid group is supportive, and symptoms usually resolve within a few hours. Gastrointestinal decontamination with oral activated charcoal is reasonable if the patient is seen early after the ingestion. Severe cases may warrant airway control or anti-seizure therapy with benzodiazepines.
Monomethylhydrazine-Containing Mushrooms
The mushroom genus Gyromitra is found during the spring months in North America and Europe. These unusual-appearing mushrooms with irregularly convoluted caps are known as false morels and are occasionally mistaken for true morels, which are considered a delicacy. Despite a potential for significant toxicity, Gyromitra have been canned and sold in eastern Europe, but are banned now in some countries.24
Gyromitras contain precursors to a toxin known as gyromitrin. Gyromitrin is N-methyl-N-formyl hydrazine, which is unstable, and upon hydrolysis in the body yields monomethylhydrazine (MMH). MMH is a highly reactive compound used in industry as a solvent and rocket fuel!37 These chemicals are highly volatile and, as a result, boiling will eliminate a significant percentage, but not all, of the toxins. Vapors definitely pose a hazard to the cook and, until recently, have been a hazard in the canning industry.24,38
Similar to the clinical effects of isoniazid, which is chemically related to MMH and is a hydrazine derivative, the hydrazine toxins of Gyromitra interfere with pyridoxine dependent enzymes used for the production of acid GABA in the brain. This leads to lack of GABA, which can result in seizures.8,38-40
Clinical Syndrome. Like the mushroom toxins in group I and IA, Gyromitra ingestions often have a delay prior to onset of toxic symptoms for 6-24 hours or longer.39 Initial symptoms are gastrointestinal, with abdominal pain, bloating, vomiting, and diarrhea lasting a few days.39,40 Other target involved include the liver, red blood cells, and the CNS. Late findings may include jaundice and elevation of liver enzymes. Because of its reactivity, MMH can cause oxidation of hemoglobin to methemoglobin and cause hemolysis. The CNS effects include headache, ataxia, depressed sensorium, and seizures.40
Treatment. General decontamination methods will be addressed in the final section. Seizures initially should be treated with benzodiazepines. Like isoniazid toxicity, the seizures induced by monomethylydrazine also can be treated with pyridoxine in doses of 25 mg/kg intravenously to restore GABA production in the CNS.8 Very large doses of pyridoxine can result in delayed peripheral neuropathies. Intravenous methylene blue can be used in cases with severe methemoglobinemia. Patients should be followed closely for evidence of hypoglycemia and delayed hepatotoxicity. Mortality rates have been reported to be in the range of 15% to 35%.29,39
Muscarine-Containing Mushrooms
Although muscarine was initially discovered in Amanita muscaria, much greater quantities of this toxin are present in many species of Inocybe mushrooms, and some species of Clitocybe, which are distributed worldwide. The orange luminous Jack-O-Lantern mushroom (Omphalotus illudens and O. oleareus), which is often mistaken for the yellow edible chanterelle, has previously been classified in the genus Clitocybe. The Jack-O-Lantern has not been definitely shown to contain muscarine, but is associated with a very similar symptom complex of acute gastrointestinal irritation, and therefore, it is mentioned in this discussion.41,42
Stimulating these receptors causes perspiration, salivation, and lacrimation (PSL syndrome) along with vomiting, diarrhea, urination, bronchorrhea, bradycardia, and pupillary constriction.41 This complex is similar to that encountered in organophosphate poisoning, but without the nicotinic effects on striated muscles. Although the GI symptoms are common to most mushroom intoxication syndromes, the PSL syndrome is unique to this group of mushrooms; fortunately, it is self-limited to less than a day.43 If a patient clearly has symptoms of cholinergic excess, the specific antidote atropine may be titrated to block the symptoms. The dose of atropine for an adult is 1-2 mg given IV slowly. For children the dosage is 0.05 mg/kg.6,41
Coprine-Containing Mushrooms
Various members of the widely disseminated genus Coprinus—in particular C. atramentarius—have the peculiar feature of only causing toxicity if consumed with alcohol. The resultant toxic symptom complex is similar to a disulfiram reaction, causing several hours of extreme unpleasantness for the victim, but is seldom life threatening. The light-colored Coprinus atramentarius is known as the "inky cap," and gets its name from its association with dung ("Coprinus") and the phenomenon of autodigestion of the gills into an inky black residue ("atramentarius") when the specimen begins to age.
The offending protoxin is coprine, an atypical amino acid. Coprine is metabolized in the body to 1-aminocyclopropanol, which is further metabolized to an intermediate that blocks the function of the enzyme aldehyde dehydrogenase.44 If ethanol is consumed, the acetaldehyde that is a normal intermediate in ethanol’s metabolism will accumulate, leading to the toxic symptoms. Coprine is not inactivated by cooking.45,46
The patient is vulnerable to the effects of coprine if alcohol is consumed shortly before and up to 72 hours after the mushroom is ingested.45 Symptoms include throbbing headache and upper body flushing from the vasodilatory effects, as well as nausea and vomiting, a metallic taste in the mouth, tachycardia, and hypotension.44 Occasional cases of atrial fibrillation are reported.46 The symptoms are self-limited, but the patient should be warned not to ingest any more alcohol for a few days.
Gastrointestinal decontamination is not necessary and syrup of ipecac, because it may contain ethanol, should be avoided. Isotonic fluid resuscitation is indicated and diphenhydramine may help the flushing. Vasopressors may occasionally be indicated. An antidote, which sould theoretically work, but has not been FDA approved is 4-methylpyrazole (4-MP).46 4-MP, which is approved for toxic alcohol ingestion (e.g., methanol), works by blocking the metabolic step before aldehyde dehydrogenase. That step is alcohol dehydrogenase; as a result, acetaldehyde is not produced after alcohol consumption.47
It should be noted there are several other drugs and chemicals that have a disulfiram-like reaction when taken with ethanol. One of the most familiar is metronidazole. Workers in the rubber industry who are exposed to tetramethylthiuram disulfide can have the same reaction if they ingest a beer after work.47 Coprine was investigated as a potential therapeutic agent for alcoholism, but was found to be carcinogenic when used long term.44
Psilocybin-Containing Mushrooms
Psilocybin-containing, or hallucinogenic, "magic" mushrooms have been popular in the drug culture for the past last 30 years. Their popularity was a consequence of the rediscovery during the 1950s of "teonanacatl" ("flesh of the gods"), which was the psilocybe mushroom used in Mexican Aztec religious rituals as long as 2000 years ago. The discoverer of lysergic acid diethylamide (LSD), the organic chemist Dr. Albert Hofman, also isolated psilocybin and psilocin, the active hallucinogens in some Psilocybe, Panaeolus, and Gymnopilus species of mushrooms. These mushrooms are distributed worldwide, and Gymnopilus spectabilis is known as the "big laughing mushroom" in Japan.48 Hallucinogens were briefly used in legitimate psychiatric research in the 1950s and 60s but became rapidly adapted as pleasure drugs in the hippie movement of the 1960s.49
Magic mushroom growing spore kits have been available through mail order in drug-oriented periodicals for many years, and they are now available for credit card purchase at various Web sites on the Internet. Possession of psilocybin mushrooms is illegal but possession or shipment of spores may not be.50 Various surveys of college students indicate 10-15% of them have tried "shrooms" at least once.50,51
Several species of psilocybe mushrooms are indigenous to the United States, particularly in moist fertile areas of the Northwest and Southeast. "Magic" mushrooms sold on the street often contain no psilocybin, but instead may represent commercial mushrooms laced with LSD or phencyclidine.48 The largest percentage of mushroom exposures reported to poison control centers, other than unknowns, are hallucinogenic.3,52 There are a few hundred reports of hallucinogenic mushrooms ingestions to poison centers yearly, but this represents only a tiny fraction of the actual ingestions.
Hallucinogenic mushrooms vary widely in their psilocybin content, some requiring ingestion of only a few specimens; and some, like Psilocybe semilanceata (Liberty caps), 20-40 fresh specimens must be ingested for an adequate dose.48 This explains the frequent gastrointestinal symptoms associated with these ingestions, inasmuch as large quantities of mushrooms may be difficult to digest or may contain other toxins. Several species of hallucinogenic mushrooms have the characteristic of turning blue when bruised, but this neither necessarily indicates hallucinogen content nor confirms lack of other toxicity.48,50,53
Clinical Syndrome. Psilocybin and psilocin are indole derivatives, and therefore, are closely related to serotonin, LSD, and tryptophan. Symptoms begin shortly after ingestion, usually within one hour, and typically last 2-4 hours.48 Gastrointestinal side effects are common. Sympathomimetic effects also accompany the perceptual changes, and include tachycardia, mydriasis, and occasional hypertension.48,54 The hallucinations produced by psilocybin and other psychedelic "mind-expanding" drugs are distinct from those produced by toxic amounts of other drugs such as anticholinergics and cocaine and withdrawal states. The hallucinations consist of altered or heightened sensory perceptions ("hearing colors" or "seeing music"), altered time, or visual distortions. The individual may experience these perceptions with a sense of religious exhalation or may become very frightened.
Commonly cited is the feeling of being outside one’s self, observing; also commonly reported is the sensation or feeling of a union with mankind or the cosmos.55
The effects last a few hours. Occasional overdoses may result in a more prolonged toxic psychosis. Seizures and hyperthermia have been occasionally reported in children.48 Accidental trauma such as jumping off a roof while thinking one can fly is another consequence. Treatment of the ingestion usually is not necessary. Assurance and a calm environment often suffice. Benzodiazepines are the drugs of choice for agitation.54
Gastrointestinal Irritants
This final and largest category also qualifies as a "miscellaneous" since many varieties of mushrooms that have not been mentioned in previous categories may lead to GI upset. The most commonly ingested mushroom from this group is Chlorophyllum molybdites (also known as Lepiota morgani or the green parasol mushroom), which grows throughout the United States and much of the southern hemisphere. This is a large, light-colored mushroom with grayish green gills and is often mistaken as edible or is eaten by young children. This mushroom produces symptoms that begin quickly (within 30 minutes to two hours after ingestion), and are characterized by intense nausea, vomiting, and diarrhea. Clinical shock from severe dehydration is possible.56,57
Chlorophyllum can occasionally cause disseminated intravascular coagulation and obtundation but these are rare.56,58 The toxins involved have not been elucidated. Most cases are self-limited and require only fluid resuscitation, electrolyte monitoring, and symptomatic treatment. There is variable susceptibility among individuals, so some may become ill when others do not.5
Approach to Mushroom Ingestion
There are several questions that should be asked in cases of suspected mushroom poisoning:1,2,6
1. How long after mushroom consumption did symptoms begin? (A latency period of six hours or greater suggests exposure to the more poisonous groups: I, IA, or III.)
2. Was more than one type of mushroom consumed? (The prolonged latency period of a more toxic mushroom could be masked, leading to a false sense of security.)
3. What were the initial symptoms? (Autonomic symptoms, inebriation, or hallucinations suggests groups: II, IV, V, or VI.)
4. Was alcohol consumed within 72 hours after mushroom ingestion? (Autonomic symptoms and GI upset suggest group V.)
5. Did everyone who ate the mushrooms become ill? (If only one person became ill, this might represent food sensitivity or an unrelated illness.)
6. Did anyone who did not eat the mushrooms become ill? (This suggests food poisoning or infectious gastroenteritis.)
7. How were the mushrooms collected, prepared, and stored? (Again, consider the possibility of bacterial contamination.)
8. Were the mushrooms collected on a golf course, public park, or transportation right-of-way? (Mushrooms can cause illness if contaminated by fertilizers, insecticides, or herbicides.)
Symptomatic patients should be admitted for observation until symptoms resolve. Patients with delayed symptoms should be admitted to the hospital for monitoring and treatment while an attempt is made to identify the mushroom, to exclude cyclopeptide, orellanine, or gyromitrin poisoning. If follow-up of a patient cannot be assured, admission for 3-5 days also should be considered.6,8
Gastrointestinal decontamination methods should be individualized to each patient’s circumstance. Only very recent ingestions (1-2 hours) would have any benefit from ipecac or gastric lavage. Administration of ipecac will confuse the clinical picture by causing vomiting, yet it maybe more efficacious than lavage at retrieving larger undigested pieces of mushroom. Administration of activated charcoal is a very reasonable, and perhaps preferable, alternative.1,5,59
Close attention should be paid to the patient’s vital signs, glucose, and fluid and electrolyte status. Fluid resuscitation and symptomatic treatment will be adequate in the majority of cases. Thorough discharge instructions alerting the patient to delayed symptoms and follow-up arrangements should be provided.8
As mushroom hunting for food and thrill seeking is rising, emergency physicians will continue to be called upon to treat these patients. Knowledge of the types of toxins and their clinical features, along with a plan for mushroom identification and appropriate treatment will contribute to a successful outcome.
References
1. McPartland JM, Vilgalys RJ, Cubeta MA. Mushroom poisoning. Am Fam Physician 1997;55:1797-1800, 1805-1809, 1811-1812.
2. Blackman JR. Clinical approach to toxic mushroom ingestion. J Am Board Fam Pract 1994;7:31-37.
3. Livovitz TL, Klein-Schwartz W, Caravati EM, et al. 1998 Annual Report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med 1999;17:435-487.
4. Trestrail JH. Mushroom poisoning in the United States—An analysis of 1989 United States Poison Control Center data. J Toxicol Clin Tox 1991;29:459-465.
5. Schneider SM, Cochran KW, Krenzlok EP. Mushroom poisoning: Recognition and emergency management. Emerg Med Rep 1991;12:81-88.
6. Poisondex System: Toxicologic Management. Mushrooms. In: Rumack BH, Sayre NK, Gelman CR, eds. Poisondex System. Englewood, Colorado: Micromedex; Ed expires 6-30-99.
7. Spoerke DG. Introduction to Identification and Toxicology. In: Spoerke DG, Rumack BH, eds. Handbook of Mushroom Poisoning, Diagnosis and Treatment. Boca Raton, FL: CRC Press; 1994:1-8.
8. Goldfrank LR. Mushrooms: Toxic and Hallucinogenic. In: Goldfrank LR, Flomenbaum NE, Lewis NA, eds. Goldfrank’s Toxicological Emergencies. 6th ed. Stamford Conn: Appleton and Lange; 1998:1207-1220.
9. Grimes GL. Principles of Mushroom Identification. In: Spoerke DG, Rumack BH, eds. Handbook of Mushroom Poisoning, Diagnosis and Treatment. Boca Raton, FL: CRC Press; 1994:65-96.
10. Jacobs J, VonBehren J, Kreutzer R. Serious mushroom poisoning in California requiring hospital admission, 1990 through 1994. West J Med 1996;165:318-319.
11. Lipske M. A new gold rush packs the woods in Central Oregon. Smithsonian 1994;24:35-45.
12. Warden CR, Benjamin DR. Acute renal failure associated with suspected Amanita smithsonia. Mushroom Ingestions: A case series. Acad Emerg Med 1998;5:808-812.
13. Leathem AM, Purssell RA, Chan VR et al. Renal failure caused by mushroom poisoning. Toxicol Clin Tox 1997;35:67-75.
14. Shaw M. Amateur Opportunity. In: Spoerke DG, Rumack BH, eds. Handbook of Mushroom Poisoning, Diagnosis and Treatment. Boca Raton, FL: CRC Press; 1994:9-38.
15. McClain JL, Hause DW, Clark MA. Amanita phalloides mushroom poisoning: A cluster of four fatalities. J Forensic Sci 1989;34:83-87.
16. Klein AS, Hart J, Brems JJ, et al. Amanita poisoning: Treatment and the role of liver transplantation. Am J Med 1989;86:187-193.
17. Larrey D, Pageaux GP. Hepatotoxicity of herbal remedies and mushrooms. Semin Liver Dis 1995;15:183-188.
18. Pacioni G, Lincott G. Simon & Schuster’s Guide to Mushrooms. New York: Simon & Schuster; 1981.
19. Poisondex System: Toxicologic Management. Mushrooms-Cyclopeptides. In: Rumack BH, Sayre NK, Gelman CR, eds. Poisondex System. Englewood, CO., Micromedex, Ed expires 6-30-99.
20. Gillman L. Identification of Common Poisonous Mushrooms. In: Spoerke DG, Rumack BH, eds. Handbook of Mushroom Poisoning, Diagnosis and Treatment. Boca Raton, Fla: CRC Press; 1994:97-130.
21. Köppel C. Clinical symptomatology and management of mushroom poisoning. Toxicon 1993;31:1513-1540.
22. Pinson CW, Daya MR, Benner KH, et al. Liver transplantation for severe Amanita phalloides mushroom poisoning. Am J Surg 1990;159:493-499.
23. Vetter J. Toxins of Amanita phalloides. Toxicon 1998;36:13-24.
24. Chilton WS. The Chemistry and Mode of Action of Mushroom Toxins. In: Spoerke DG, Rumack BH, eds. Handbook of Mushroom Poisoning, Diagnosis and Treatment. Boca Raton, FL: CRC Press; 1994:165-233.
25. Cappell MS, Hassan T. Gastrointestinal and hepatic effects of Amanita phalloides ingestion. J Clin Gastroenterol 1992;15:225-228.
26. Shakil AO, Mazariegos GV, Kramer DJ. Fulminant hepatic failure. Surg Clin North Am 1999;79:77-108.
27. Faulstich H, Zilker TR. Amatoxins. In: Spoerke DG, Rumack BH, eds. Handbook of Mushroom Poisoning, Diagnosis and Treatment. Boca Raton, FL: CRC Press; 1994:233-249.
28. Schneider SM, Borochovitz D, Krenzlok EP. Cimetidine protection against alpha-Amanitin hepatotoxicity in mice: A potential model for the treatment of Amanita phalloides poisoning. Am Emerg Med 1987;16:1136-1140.
29. Schneider SM. Mushroom Toxicity. In: Auerbach PS. Wilderness medicine, Management of Wilderness and Environmental Emergencies. 3rd ed. St. Louis: Mosby; 1995:891-907.
30. Meunier B, Camus CM, Houssin DP, et al. Liver transplantation after severe poisoning due to Amatoxin-containing Lepiota—Report of three cases. J Toxicol Clin Txi 1995;33:165-171.
31. Horn S, Horina JH, Krejs GJ, et al. End-stage renal failure from mushroom poisoning with Cortinarius orellanus: Report of four cases and review of the literature. Am J Kidney Dis 1997;30:282-286.
32. Poisondex System: Toxicologic Management. Mushrooms-Cyclopeptides. In: Rumack BH, Sayre NK, Gelman CR, eds. Poisondex System. Englewood, CO: Micromedex; Ed expires 6-30-99.
33. Jaeger A. Orellanine Mushrooms. In: Spoerke DG, Rumack BH, eds. Handbook of Mushroom Poisoning, Diagnosis and Treatment. Boca Raton, FL: CRC Press; 1994:249-264.
34. Bouget J, Bousser J, Pats B. Acute Renal Failure following collective intoxication by Cortinarius orellanus. Intens Care Med 1990;16:506-510.
35. Hall AH, Hall K. Ibotenic Acid/Muscimol Containing Mushrooms. In: Spoerke DG, Rumack BH. eds. Handbook of Mushroom Poisoning, Diagnosis and Treatment. Boca Raton, FL: CRC Press; 1994:265-278.
36. Poisondex System: Toxicologic Management. Mushrooms-Muscimol/Ibotenic Acid. In: Rumack BH, Sayre NK, Gelman CR, eds. Poisondex System. Englewood, CO: Micromedex; Ed expires 6-30-99.
37. Sullivan JB. Cryogenics, Oxidizers, Reducing Agents and Explosives. In: Sullivan JB, Krieger GR, eds. Hazardous Materials Toxicology, Clinical Principles of Environmental Health. Baltimore, MD: Williams & Wilkins; 1992:1192-1201.
38. Michelot D, Toth B. Poisoning by Gyromita esculenta—A Review. J Appl Toxicol 1991;11:235-243.
39. Poisondex System: Toxicologic Management. Mushrooms-Monomethylhydrazine. In: Rumack BH, Sayre NK, Gelman CR, eds. Poisondex System. Englewood, CO: Micromedex; Ed expires 6-30-99.
40. Trestrail JH. Monomethylhydrazine-Containing Mushrooms. In: Spoerke DG, Rumack BH, eds. Handbook of Mushroom Poisoning, Diagnosis and Treatment. Boca Raton, FL: CRC Press; 1994:279-288.
41. Young A. Muscarine-Containing Mushrooms. In: Spoerke DG, Rumack BH, eds. Handbook of Mushroom Poisoning, Diagnosis and Treatment. Boca Raton, FL: CRC Press; 1994:289-302.
42. French AL, Garrettson LK. Poisoning with the North American Jack O’Lantern Mushroom, Omphalotus illudens. J Toxicol Clin Tox 1988:26:81-88.
43. Mitchell DH, Rumack BH. Symptomatic Diagnosis and Treatment of Mushroom Poisoning. In: Rumack BH, Salzman E, eds. Mushroom Poisoning: Diagnosis and Treatment. West Palm Beach, FL: CRC press; 1978:171-180.
44. Michelot D. Poisoning by Coprinus atramentarius. Natural Toxins 1992;1:73-80.
45. Kunkel DB, Connor DA. Coprine-Containing Mushrooms. In: Spoerke DG, Rumack BH. eds. Handbook of Mushroom Poisoning, Diagnosis and Treatment. Boca Raton, FL: CRC Press; 1994:303-308.
46. Poisondex System: Toxicologic Management. Mushrooms-Coprine. In: Rumack BH, Sayre NK, Gelman CR, eds. Poisondex System. Englewood, CO: Micromedex, Ed expires 6-30-99.
47. Goldfrank LR. Disulfiram and Disulfiram-like Reactions. In: Goldfrank LR, Flomenbaum NE, Lewin NA, et al. Goldfrank’s Toxicologic Emergencies. 6th ed., Stamford, Connecticut: Appleton and Lange; 1998:1043-1048.
48. Smolinske SC. Psilocybin-Containing Mushrooms. In: Spoerke DG, Rumack BH, eds. Handbook of Mushroom Poisoning, Diagnosis and Treatment. Boca Raton, FL: CRC Press; 1994:309-324.
49. Hofmann A. LSD, My Problem Child. New York, NY: JP Tarcher/Perigree Books; 1983.
50. Schwartz RH, Smith DE. Hallucinogenic mushrooms. Clin Peds 1988;27:70-73.
51. Webb E, Ashton CH, Kelly P. Alcohol and drug use in UK University Students. Lancet 1996;348:922-925.
52. Litovitz TL, Klein-Schwartz W, Dyer KS, et al. 1997 Annual Report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med 1998;16:443-490.
53. Lincoff G, Mitchel DH. Toxic and Hallucinogenic Mushroom Poisoning, A Handbook for Physicians and Mushroom Hunters. New York: Van Nostrand Reinhold Co.; 1977:100-136.
54. Poisondex System: Toxicologic Management. Mushrooms-Hallucinogenic. In: Rumack BH, Sayre NK, Gelman CR. eds: Poisondex System. Englewood, CO: Micromedex; Ed expires 6-30-99.
55. Jaffe JH. Drug Addiction and Drug Abuse. In: Goodman Gilman A, Rall TW, Nies AS, et al, eds. Goodman and Gilman’s The Pharmacologic Basis of Therapeutics, 8th ed. New York: Pergamon Press; 1990:522-573.
56. Poisondex System: Toxicologic Management. Mushrooms-Chlorophyllum. In: Rumack BH, Sayre NK, Gelman CR, eds. Poisondex System. Englewood, CO: Micromedex; Ed. expires 6-30-99.
57. Stenklyft PH, Augenstein WL. Chlorophyllym molybdites—Severe mushroom poisoning in a child. J Toxicol Clin Tox 1990;28:159-168.
58. Augenstein WL. Chlorophyllum molybdites. In: Spoerke DG, Rumack BH, eds. Handbook of Mushroom Poisoning, Diagnosis and Treatment. Boca Raton, FL: CRC Press; 1994:325-338.
59. Rumack BH. Symptomatic Diagnosis and Treatment of Mushroom Poisoning. In: Spoerke DG, Rumack BH. eds. Handbook of Mushroom Poisoning, Diagnosis and Treatment. Boca Raton, FL: CRC Press; 1994:149-164.
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