Mushroom Toxicity (2024)

Continuing Education Activity

The term mushroom refers to the fungal fruiting body. Anatomically, the prototypical mushroom comprises the stem and a cap with gills on the underside. However, the term may refer to many stemless gilled fungi with varying forms such as the "morel," "puffball," or "stinkhorn." The gills of the mushroom produces spores which aid in the propagation of the fungus itself. Mushroom toxicity has also been known for millennia and is implicated in the death of several historical figures, including the Roman Emperor Claudius. This activity reviews the cause, pathophysiology, and presentation of mushroom toxicity and highlights the role of the interprofessional team in its management.

Objectives:

Describe the pathophysiology of mushroom toxicity.
Review the presentation of a patient with mushroom toxicity.
Summarize the treatment options for mushroom toxicity.
Explain modalities to improve care coordination among interprofessional team members in order to improve outcomes for patients affected by mushroom toxicity.

Access free multiple choice questions on this topic.

Introduction

Humans have consumed mushrooms since prehistory. Mushroom toxicity has also been known for millennia and is implicated in the death of several historical figures, including the Roman Emperor Claudius.[1] Today most mushrooms are farmed commercially, but foraging for mushrooms is on the rise as a recreational endeavor.

Mushroom poisonings can occur because of forager misidentification of a poisonous species as edible, although many cases are intentional ingestions.Mushroom poisonings may range from benign symptoms of generalized gastrointestinal upset to potentially devastating manifestations which include liver failure, kidney failure, and neurologic sequelae. There are up to 14 described syndromes, which manifest depending on the species, toxins, and amount ingested.

Etiology

The symptoms of mushroom poisoningrelateto the toxin ingested, includingamatoxin, psilocybin, muscarine, coprine, allenic norleucine, gyromitrin, etc.

Epidemiology

Of the vast numberof 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, andPanaeolus. These agentsact 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 speciesin various genera such as cl*tocybe 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 asCoprinus 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 ofcoprine-containing mushrooms.Co-ingestion of alcohol and the toxin leads to lessened effects because ofthe 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 smithianais 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 consumeGyromitra. 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 theevaluation 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 bythe 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 possiblesymptoms primarily consists of supportive care.

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

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 fromthe 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.

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 usuallywill 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 torenal failure,liver failure, and death in severe toxicities.

Deterrence and Patient Education

Most mushroom poisonings result in mild to moderate gastrointestinal manifestations which include nausea, vomiting, and diarrhea. However, there is a variety of sequelaethat lead to organ failure and even death. Foragers must know the vast number of differing mushroom species and potential look-a-likes; this is particularlytrue for those new to the hobby. Knowledge of local edible and toxic mushroom species is paramount for amateur foragers. Even mild nausea will require evaluation as this could be an early manifestation of severe illness.

Enhancing Healthcare Team Outcomes

Mushroom toxicity has a broad range of manifestations and will require an interprofessional approach to care for the patient. Nursing staff and physicians must know the possibility that nonspecific gastrointestinal symptoms could be secondary to mushroom toxin ingestion, which will depend largelyon the local geography. If this diagnosis is not on the differential, treatment cannot be efficient and timely. Technicians and nurses are paramount in the patient's care as they will have the most time bedside evaluating for any changes or decompensation. For many of these toxidromes, the early presentation may appear benign, but over the course ofhours, the patient may continue to deteriorate. The medical team should reach out expeditiously to local poison control centers for additional resources and recommendations. Pharmacists shouldbe consulted early as most of the medications (N-acetylcysteine, pyridoxine, etc.) are not readily available.

As with many other toxic ingestions and wilderness medicine, most of the data about management and treatment in specific mushroom poisonings comes from case reports, case studies, or expert opinion (Level V). Management of most mushroom ingestions is with supportive care. The management of renal, liver, and neurologic manifestations should take place in consultationwith specialists in those respective fields. Administration of antidotes such as N-acetylcysteine, pyridoxine, methylene blue, atropine, and glycopyrrolateshould be per toxicologist recommendations.

Review Questions

Figure

Types of toxic mushrooms Image courtesy S Bhimji MD

References

1.: Marmion VJ, Wiedemann TE. The death of Claudius. J R Soc Med. 2002 May;95(5):260-1. [PMC free article: PMC1279685] [PubMed: 11983773]
2.: Bronstein AC, Spyker DA, Cantilena LR, Green JL, Rumack BH, Giffin SL. 2008 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 26th Annual Report. Clin Toxicol (Phila). 2009 Dec;47(10):911-1084. [PubMed: 20028214]
3.: Beuhler MC, Sasser HC, Watson WA. The outcome of North American pediatric unintentional mushroom ingestions with various decontamination treatments: an analysis of 14 years of TESS data. Toxicon. 2009 Mar 15;53(4):437-43. [PubMed: 19708122]
4.: Lehmann PF, Khazan U. Mushroom poisoning by Chlorophyllum molybdites in the Midwest United States. Cases and a review of the syndrome. Mycopathologia. 1992 Apr;118(1):3-13. [PubMed: 1406900]
5.: Dinis-Oliveira RJ. Metabolism of psilocybin and psilocin: clinical and forensic toxicological relevance. Drug Metab Rev. 2017 Feb;49(1):84-91. [PubMed: 28074670]
6.: Michelot D. Poisoning by Coprinus atramentarius. Nat Toxins. 1992;1(2):73-80. [PubMed: 1344910]
7.: Diaz JH. Amatoxin-Containing Mushroom Poisonings: Species, Toxidromes, Treatments, and Outcomes. Wilderness Environ Med. 2018 Mar;29(1):111-118. [PubMed: 29325729]
8.: Dinis-Oliveira RJ, Soares M, Rocha-Pereira C, Carvalho F. Human and experimental toxicology of orellanine. Hum Exp Toxicol. 2016 Sep;35(9):1016-29. [PubMed: 26553321]
9.: Mancini A, Assisi F, Balestreri S, Angelini P, Bozzi M, Cuzzola C, Davanzo F, Giancaspro V, Laraia E, Nisi MT, Proscia A, Tarantino G, Vitale O, Petrarulo F. [A rare case of acute renal failure related to amanita proxima ingestion]. G Ital Nefrol. 2015 Jul-Aug;32(4) [PubMed: 26252264]
10.: Kirchmair M, Carrilho P, Pfab R, Haberl B, Felgueiras J, Carvalho F, Cardoso J, Melo I, Vinhas J, Neuhauser S. Amanita poisonings resulting in acute, reversible renal failure: new cases, new toxic Amanita mushrooms. Nephrol Dial Transplant. 2012 Apr;27(4):1380-6. [PubMed: 21965588]
11.: Lheureux P, Penaloza A, Gris M. Pyridoxine in clinical toxicology: a review. Eur J Emerg Med. 2005 Apr;12(2):78-85. [PubMed: 15756083]
12.: Danel VC, Saviuc PF, Garon D. Main features of Cortinarius spp. poisoning: a literature review. Toxicon. 2001 Jul;39(7):1053-60. [PubMed: 11223095]
13.: Leathem AM, Dorran TJ. Poisoning due to raw Gyromitra esculenta (false morels) west of the Rockies. CJEM. 2007 Mar;9(2):127-30. [PubMed: 17391587]
14.: Karvellas CJ, Tillman H, Leung AA, Lee WM, Schilsky ML, Hameed B, Stravitz RT, McGuire BM, Fix OK., United States Acute Liver Failure Study Group. Acute liver injury and acute liver failure from mushroom poisoning in North America. Liver Int. 2016 Jul;36(7):1043-50. [PubMed: 26837055]
15.: Pauli JL, Foot CL. Fatal muscarinic syndrome after eating wild mushrooms. Med J Aust. 2005 Mar 21;182(6):294-5. [PubMed: 15777146]

: Disclosure: Huu Tran declares no relevant financial relationships with ineligible companies.
: Disclosure: Andrew Juergens declares no relevant financial relationships with ineligible companies.