Mushroom Toxicity

Etiology

The symptoms of mushroom poisoning relate to the toxin ingested, including amatoxin, psilocybin, muscarine, coprine, allenic norleucine, gyromitrin, etc. 

Epidemiology

Of the vast number of mushroom species, there are only approximately 100 that are toxic. There are about 6000 ingestions annually in the United States.  Of these, over half of the exposures are in children under six years.  Most poisonings exhibit symptoms only of gastrointestinal upset, which is a common feature across several toxidromes and is most likely to occur with ingestions of small quantities of toxic mushrooms.  Severe poisonings, when they take place, are primarily a consequence of misidentification by adults foraging for wild mushrooms who consume them as a food source.[2][3]

Pathophysiology

The clinical presentation differs depending on the species of mushroom and toxin ingested.

Acute gastroenteritis: Most often secondary to one of a variety of “backyard mushrooms” such as Chlorophyllum molybdites. Symptoms of nausea, vomiting, abdominal cramping and possibly diarrhea associated with ingestion account for the vast majority of reported poisonings. It manifests typically within 1-3 hrs.[4]

Hallucinations: Caused by psilocybin and psilocin containing species which include Psilocybe, Conocybe, Gymnopilus, and Panaeolus. These agents act as agonists or partial agonists at 5-hydroxytryptamine (5-HT) subtype receptors.[5] These are grown and abused for recreational purposes, though they may grow naturally in warm, moist climates. Ingestion may be of fresh mushroom caps or dried mushrooms. Altered sensorium and euphoria occur 30 minutes to 2 hours after ingestion and last typically 4–12 hours depending on the amount. 

Cholinergic toxicity: Caused by muscarine containing species in various genera such as Clitocybe and Inocybe. Though Amanita muscari contains small amounts of muscarine, levels are typically not sufficient to cause a cholinergic presentation. Cholinergic effects of abdominal cramping, diaphoresis, salivation, lacrimation, bronchospasm, bronchorrhea, and bradycardia usually occur within 30 minutes. Duration is dose-dependent though typically short-lived when compared to other sources of cholinergic poisoning such as pesticides.

Disulfiram-like reaction: Caused by coprine-containing species such as Coprinus atramentarius (“inky cap”). The toxin’s metabolites result in aldehyde dehydrogenase inhibition leading to headache, nausea, vomiting, flushing, tachycardia, and rarely hypotension. This only occurs if alcohol is ingested hours to days after the consumption of coprine-containing mushrooms. Co-ingestion of alcohol and the toxin leads to lessened effects because of the slower metabolism of coprine to its toxic metabolites.[6] 

Liver toxicity: Caused by amatoxin in species of Galerina, and Lepiota and especially Amanita.[7]  They disrupt RNA polymerase II, leading to protein deficiency at the cellular level.  Toxicity characteristically demonstrates three distinct phases. Gastrointestinal effects start typically 6-12 hours post-ingestion, followed by a quiescent interval 24-36 hours after ingestion with symptomatic improvement. During this phase, however, there may be laboratory signs of hepatotoxicity. After 48 hours, hepatic damage intensifies, leading to liver failure and its sequelae. Death may occur within a week in severe cases or require liver transplantation.

Nephrotoxicity: Members of the Cortinarius genus produce orellanine, a nephrotoxic agent.  Renal symptoms may delay for 1-2 weeks after ingestion.[8] Nephrotoxicity also results from allenic norleucine found most commonly in Amanita smithiana, but present in other Amanita species. Amanita smithiana is prevalent in the Pacific Northwest of the United States.[9] The typical presentation includes acute gastroenteritis symptoms progressing to renal injury in 12-24 hrs. Although some patients will require hemodialysis, most patients have a full recovery with appropriate supportive care.[10] 

Seizures: Caused by gyromitrin present in Gyromitra, Paxina, and Cyathipodia micropus species, though the latter two are far less common. Foragers looking for morel (Morchella esculenta) may mistakenly consume Gyromitra. Toxicity stems from a metabolite, monomethylhydrazine, that leads to pyridoxine (B6) and ultimately GABA depletion. Because of this, these seizures may be intractable to anticonvulsant therapy and may require supplemental treatment including pyridoxine.[11]

Other manifestations: Given the broad range of mushrooms that could be ingested, multiple other clinical manifestations can occur. These include but are not limited to headaches, vertigo, somnolence, palpitations, dysrhythmias, rhabdomyolysis (Tricholoma equestre), methemoglobinemia, hemolysis (Paxillus involutus), erythromelalgia (acromelic acid), dermatitis (shiitake mushrooms), and cramping.

History and Physical

History components that are helpful to relay to your local poison control center include:

• Description of the mushroom including color, texture, cap appearance (brain-like, smooth, small, large)
• How much was eaten? In the evaluation of possible Coprinus consumption, was there any concomitant alcohol intake?
• The onset of symptoms after ingestion, though note that if there is more than one type of mushroom ingested, acute as well as delayed symptoms may occur.
• Location and season of collection, given that some mushrooms are preserved and eaten at a later time
• Are any additional people that consumed the mushrooms ill?

Physical examination findings are nonspecific and again, vary depending on the mushroom ingested. In addition to a thorough physical exam, evaluate for signs of:

• Dehydration secondary to gastroenteritis
• Cholinergic toxicity
• Liver dysfunction
• Systemic allergic reactions

Evaluation

Testing should be guided by the presentation and may include:

• Observation without testing in asymptomatic low-risk patients
• Serum electrolytes, kidney function testing, urinalysis
• Serum CK
• Liver enzymes, coagulation studies
• Complete blood count

In severely symptomatic patients, target additional studies based on the presentation of hepatic failure, altered mental status, hypoxia or respiratory distress.

Treatment / Management

Treatment of the vast array of possible symptoms primarily consists of supportive care.

Depending on the timing of ingestion, activated charcoal may provide some benefit. 

Acute gastrointestinal effects may benefit from rehydration and antiemetics in addition to correction of any electrolyte derangements. For those patients with adverse hallucinations, benzodiazepines may provide anxiolysis. Cholinergic toxicity may benefit from the administration of anticholinergic agents such as glycopyrrolate or atropine.  Consider Atropine 0.5-1mg IV adults or 0.01mg/kg for pediatric patients. 

Specifically, for patients with refractory seizures secondary to gyromitra ingestion, pyridoxine (B6) should be administered. Pyridoxine at 25 mg/kg IV can be given as treatment or prophylactically for seizure control. Benzodiazepines may be a helpful adjunct. 

Specifically, for patients ingesting amatoxin, consider N-acetylcysteine (NAC), silibinin, and penicillin.

Practitioners should evaluate and manage patients in consultation with the local poison control center or toxicology resource.

Differential Diagnosis

• Gastroenteritis
• Foodborne toxin
• Acute viral hepatitis 
• Acetaminophen overdose/toxicity
• Ischemic hepatitis
• Alcoholic hepatitis
• Isoniazid toxicity (for refractory seizures in gyromitra ingestions)
• Organophosphate toxicity 
• Carbamate toxicity

Prognosis

Most mushroom ingestions which present with gastrointestinal symptoms will recover without complication when provided adequate supportive care. 

For patients with Cortinarius ingestion, one study found that 68% had evidence of renal impairment with 51% requiring hemodialysis and 11% developing end-stage renal failure. Out of the cohort of 90 patients, 12 ultimately received kidney transplantation.[12]

For those with Gyromitra ingestion, most of these patients return to health within one week with the initiation of prompt seizure management and supportive care. One Eastern European study found a 10% mortality rate.[13]

For patients with Amanita toxicity, one review showed that 2% of patients ultimately required liver transplantation. Patients with mild hepatotoxicity usually will recover.[14]

Patients with mild anticholinergic toxicity will typically recover though there have been reports of refractory bradycardia, shock, and death in severe anticholinergic toxicity.[15]

Complications

Complications of ingestion depend on the toxin ingested and may range from dehydration in benign cases to renal failure, liver failure, and death in severe toxicities.