Despite cultural changes over the past decades, mushroom ingestions, particularly toxic mushroom ingestions, are becoming more common.

According to the American Association of Poison Control Centers, there were 7,733 mushroom exposures in the United States in 2007, and nearly 35% of those exposures resulted in health care facility visits.¹ A smaller 2-year study performed in Texas revealed an admission rate of 7.9% for intentional mushroom exposures.² Luckily, the vast majority of these ingestions result in minimal symptomatology, with few fatalities.

However, even in intentional ingestions, it is often difficult for emergency physicians to differentiate between potentially life-threatening ingestions and those with more benign clinical courses.

Adding to the diagnostic confusion of mycotoxic exposures is the rarity with which patients or physicians are able to identify the species of mushroom that was ingested. Regional, and especially international, variation does occur, and knowledge of prior exposures or potential pathogens in your particular area is often helpful. Further aid can sometimes be garnered by patient characteristics and the history of the ingestion.

The overwhelming majority of pediatric patients present with accidental, also known as “backyard,” ingestions. In a review of Toxic Exposure Surveillance System (TESS) data, more than 82,000 accidental ingestions of mushrooms in pediatric patients were catalogued, and just 16 cases had major effects, with no fatalities.³ Adults, on the other hand, present mainly for intentional ingestions, most commonly because of culinary use of misidentified mushrooms, illicit use of hallucinogenic mushrooms, or, more rarely, deliberate self-injurious behavior.

Experts agree that, in terms of emergency department management, a syndromic classification scheme is needed to promote accurate diagnosis and risk stratification. Multiple iterations have been proposed over the past three decades (see sidebars, p. 13).^4,5 It is also important to have knowledge of the most common mushroom species and their varied, and time-dependent, effects.

Please note that disposition recommendations are for known ingestions in the following sections, and that patients with persistent, uncontrolled symptoms following a mushroom ingestion should always be admitted.

Ibotenic Acid/Muscimol

Mushrooms containing these compounds are most commonly found in the Amanita sp., with the noted exclusion of Amanita phalloides (addressed later). They contain ibotenic acid and its metabolite, muscimol, which act in vivo like glutamic acid and GABA, respectively. Onset of symptoms is typically rapid, within 2 hours, and may produce hallucinations, dysphoria, and delirium. In children, symptoms may include seizures and myoclonus. Treatment is supportive, there are no delayed ill effects, and symptomatically controlled patients may be discharged.

Muscarine

Clitocybe and Inocybe sp. are the representative members of this toxicologic group, and predictable peripheral muscarinic effects predominate (see sidebar for the DUMBBELS mnemonic). Though atropine would be the drug of choice for symptomatic control, it is rarely needed. Symptoms develop rapidly, within 2 hours, but may persist for hours more as well. Again, symptomatically controlled patients are safe for discharge.

Psilocybin

Likely the most recognizable mushroom by name, it is also the most common identifiable mushroom to be ingested year after year.¹ Psilocybe sp. mushrooms contain the indole psilocybin, which mimics the action of serotonin in the brain. Hallucinations, which are often the intended purpose of mushroom ingestion, are common, as are tachycardia, hypertension, hyperthermia, and diaphoresis. In fact, these clinical effects may precede the hallucinations in some cases.

While psilocybin has some similarities to lysergic acid diethylamide (LSD), severe effects such as coma, malignant hyperthermia, and death have been documented only once in mushroom ingestion.⁶ Effects are very rapid, and often only reassurance is needed. However, benzodiazepines also may offer some relief. Discharge is appropriate once vital signs normalize.

Gastrointestinal Toxins

The majority of mushroom ingestions that present to health care facilities do cause some gastrointestinal (GI) upset. Multiple species are responsible for this phenomenon, and onset of nausea, vomiting, and abdominal pain rapidly follows ingestion, usually in less than 3 hours. Patients may divulge a history of foraging for edible brown mushrooms, or may admit to searching for hallucinogenic mushrooms. Care is symptomatic, and some patients may present fairly dehydrated. Disposition is similar to that in other causes of gastroenteritis.

A special case, the Paxillus sp. mushroom, merits mention in this class as well. While Paxillus sp. cases present as do other mushrooms with predominantly gastrointestinal effects, it can also cause hemolytic anemia and renal failure. Syndromic classification systems have missed this potential morbidity in the past.⁵ In patients with severe GI symptoms requiring admission, it may be useful to evaluate a blood count, metabolic panel, and urinalysis to rule out this syndrome.

Coprine

The last specific rapid-acting toxin, coprine, is found in many Coprinus sp. of mushrooms. The mushrooms are also known as “inky caps” because of the substance they produce when picked. Ingested alone, little effect is noted, but subsequent ingestion of alcohol produces a disulfiram-like reaction, with intense vomiting, tachycardia, and flushing. This is caused by inhibition of acetaldehyde dehydrogenase.⁶ Care, once again, is symptomatic, and vomiting tends to resolve in a matter of hours.

These mushroom classes have the similarity that clinical effects present rapidly following ingestion, within 3 hours in almost all cases. This important distinction led to the early syndromic classification schemes, which have been modified significantly with increasing complexity.^7,8 The following ingestions, if identified, can produce serious clinical effects, including hepatic and renal failure, seizures, and rhabdomyolysis.

Cyclopeptides

More than 90% of fatalities associated with toxic mushroom ingestion have been attributed to amatoxin-containing species such as Amanita phalloides.⁹ Gallerina sp. and Lepiota sp. are also included in this classification. Gastrointestinal effects such as nausea and vomiting are common, but tend to be delayed until 6-24 hours after ingestion, which is a subtle differentiation from the other five classifications. Unfortunately, it is not uncommon to miss or be unable to obtain this history, and thus discharge patients with this highly dangerous ingestion after their symptoms are controlled. A quiescent phase, occurring at 12–36 hours after ingestion, may falsely lead patients and physicians alike to believe that a more benign species has been consumed. However, 2-6 days after ingestion, some patients experience hepatic and renal toxicity that can lead to death.

These toxicities are caused primarily by alpha-amanitin, a cyclopeptide that is one of the deadliest naturally occurring compounds. As little as 0.1 mg/kg can be fatal, a dose that is often present in a single mushroom.⁶ The mechanism of toxicity relates to interference with RNA polymerase II, which prevents DNA transcription. While elevation of liver enzymes may begin in the quiescent phase, fulminant hepatic failure with elevated transaminases and bilirubin and coagulopathy are not present until the third stage of poisoning.

Evidence-based recommendations are difficult to find for amatoxin poisoning, but multiple recommendations do exist in the literature.

Transfer to a center capable of performing liver transplantation is mandatory if advanced poisoning with evidence of liver failure is present. Multiple studies have attempted to delineate criteria that would merit transplantation, including two of the following: grade 2 hepatic encephalopathy or higher, prothrombin time of more than twice normal despite therapy, bilirubin level greater than 25 mg/dL, and hypoglycemia requiring infusion therapy.¹⁰

Aside from transplantation, few specific therapies have been shown to have clinical benefit. Benzathine penicillin is one of the most commonly used therapeutic options but demonstrates little efficacy.¹¹ The same review showed the most favorable outcomes with silibinin, which is an extract from the milk thistle plant. Unfortunately, dosing is not standardized, and this therapy appears to be difficult to obtain in the United States.

Gyromitrin

Also known as the false morel, appropriately dubbed for its resemblance to the highly prized morel mushroom (Morchella esculenta), Gyromitra sp. mushrooms rarely can cause severe neurologic toxicity and seizures. Gastrointestinal symptoms are usually delayed at least 5-10 hours after ingestion, and most patients recover fully. However, because of metabolism, gyromitrin is converted in vitro to monomethylhydrazine, which interrupts pyridoxal-phosphate related reactions, including those involved in GABA synthesis. As GABA is an inhibitory neurotransmitter, seizures may be precipitated and can be refractory to benzodiazepine therapy. As in isoniazid overdose, which works biochemically in the same fashion, treatment should include repeated boluses of vitamin B6 (recommended dose of 70 mg/kg IV).⁶ Patients with this ingestion should be admitted for neurologic checks.

Orelline/Orellanine

Though more prevalent in Europe, Cortinarius sp. found in the United States also contain the toxic compound orellanine. With a particularly insidious course, delayed toxicity in this mushroom ingestion may not be preventable. The earliest symptoms, such as gastritis, chills, and headache, tend to occur 1 day after ingestion, but oliguric renal failure tends to begin days to weeks after ingestion. It follows a pattern of interstitial nephritis, and there is no benefit to detoxification by hemodialysis early on; but it is the mainstay of treatment once nephrotoxic damage has set in.⁹ Renal transplantation has been warranted in some cases.

Rhabdomyolysis Toxins

While the specific toxin has not yet been elucidated, certain Tricholoma sp. mushrooms have been linked to remarkable cases of rhabdomyolysis with creatine kinase levels greater than 200,000 U/L.6 In a case series involving this ingestion, all individuals had ingested the mushrooms on multiple consecutive days.¹² There were three fatalities, and autopsy revealed myocardial as well as skeletal muscle damage. Onset of symptoms was delayed, beginning 1-3 days after the last meal, and included fatigue, weakness, and myalgias.

Allenic Norleucine

Different Amanita sp. mushrooms in Europe (proxima) and the United States (smithiana) have recently challenged the long-held belief that early gastrointestinal effects following mushroom ingestion belied an overall benign clinical course. In the 1990s, both in Europe and in the Pacific Northwest of the United States, multiple patients with mushroom ingestions characterized by early gastrointestinal symptoms developed accelerated renal failure. Allenic norleucine, among other compounds, has been found to be the culprit, and toxicity is about twice as rapid as orellanine (12 hours vs. 24 hours, respectively). This particular ingestion is not accounted for by many of the earlier syndromic classification schemes, but it is included in recent work by Diaz.^7,8

Resulting renal failure has been universally responsive to hemodialysis in the case series to date. However, this ingestion has prompted local management recommendations in the Pacific Northwest to include early hemodialysis if historical, clinical, or temporal clues point to Amanita smithiana ingestion.

As previously addressed, positive identification of the mushroom species ingested is rarely possible, and in some instances, any history of ingestion can be difficult to obtain. Syndromic classification, which is an attempt to identify the mushroom species empirically based on the patient’s clinical presentation, is a more clinically oriented approach to mycotoxic presentations. The most recent classification scheme, although complicated, accounts for all current major species ingestions (see table).^7,8

Management

Syndromic classification should be used to identify the possible culprit species of mushroom in any ingestion. From this, many of the specific management details have been addressed in this article. General management of an unknown mushroom ingestion is purposefully conservative, as late effects are often quite serious.

Given the propensity for many mushrooms to affect liver and kidney function, baseline laboratory testing is indicated and can include a complete blood count, metabolic panel, liver function testing, creatine kinase, and urinalysis. Symptomatic control is a mainstay of treatment as well.

In addition, while gastric lavage is controversial in other conditions in emergency medicine, it continues to be recommended in mushroom ingestions as long as it can be completed within 6 hours of ingestion. This will allow specimens to be submitted to mycologic experts for possible identification. Multiple-dose activated charcoal is also recommended, although there is limited evidence of benefit and no randomized trials, given the sporadic nature of toxicologic exposures in general. Disposition recommendations are given for each specific mushroom classification previously addressed.

Summary

While mushroom ingestions are rare and fatalities even more uncommon, poisonings are increasing globally. Syndromic classification should be the initial aim of evaluation, and specific management then can be tailored to the most likely mushroom species.

Though rigorous evidence is lacking, gastric lavage and multiple-dose activated charcoal remain as recommendations, and symptomatic care is all that is needed in the majority of ingestions.

Delayed onset of symptoms should raise a red flag for potentially serious outcomes. New mushroom species have been included in the most recent classification schemes.

References

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12. Bedry R, Baudrimont I, Deffieux G, et al. Wild-mushroom intoxication as a cause of rhabdomyolysis. N. Engl. J. Med. 2001;345:798-802.