Mushroom Toxicity

OVERVIEW

Mushrooms are the macroscopic fleshy, spore-bearing fruiting body of a fungus, typically produced above ground on soil or on its food source.

• severe toxicity from mushrooms is rare in humans
• most symptomatic presentations are a self-limiting gastroenteritis requiring supportive care only
• lethal hepatotoxicity from Amanita mushrooms must be excluded
  • very rare in Australia
  • accounts for most mushroom related deaths worldwide
• mushroom identification is very difficult (requires a mycologist) and is often impossible (e.g. mushrooms are unavailable, decomposing, cooked, or partially digested)

EXPOSURE

• mushroom toxicity typically occurs from:
  • incorrect collection, preparation, and/or storage of wild edible mushrooms (Gawlikowski et al, 2014)
  • when wild toxic mushrooms are misidentified as an edible species
• may present as clusters with more than one person poisoned

SYNDROMES OF MUSHROOM TOXICITY

Clinical presentations can be categorised as:

• early onset (<6 hours)
• late onset (6-24 hours)
• very late onset (>24 hours)

EARLY ONSET (<6 HOURS)

Gastrointestinal (GI), e.g. many mushroom species

• toxic mechanisms uncertain
• GI symptoms with onset 30min-3h and resolution in 6-24h

Cholinergic, e.g. Citocybe and Inocybe species

• muscarine-mediated
• 30min-2h: cholinergic syndrome

Hallucinogenic, e.g. Psilocybin spp

• psilocybin-mediated
• onset in minutes: anxiety, mydriasis, ataxia, tachycardia, dyskinesia, hallucinations, delirium

Disulfram-like; e.g. Coprinus spp

• coprine-mediated
• <2h of mushroom ingestion with prior ethanol consumption, lasts 6 hours: N&V, flushing, tachycardia, sweating, chest pain

Glutaminergic, e.g. Amanita muscaria and panterina

• 30min-2h: delirium, dysphoria, drowsiness, hallucinations, myoclonus, hyperreflexia, seizures

Epileptogenic, e.g. Gyromitra spp

• gyromitrin-mediated symptoms
• <6h: GI symptoms
• CNS symptoms: headache, ataxia, fatigue, nystagmus, tremor, vertigo, seizures (rare)
• 2-3 days: delayed hepatotoxicity (rare)
• 1-3 days after hepatotoxicity: haemolysis and methaemoglobinaemia

Immunohaemolytic, e.g. Paxillus spp

• <3h: GI symptoms
• days: haemolytic anemia, immune-complex nephritis and renal failure

Pneumonic, e.g. inhalation of dried Lycoperdonosis spores

• <6h: N&V, rhinitis
• days: pneumonia

LATE ONSET (6-24 HOURS)

Hepatotoxic, e.g Amanita, Galerina and Lepiota spp

• hepatotoxic cyclopeptides: amatoxins, phallotoxins and virotoxins
• 6-24h: GI symptoms
• 18-36h: transient improvement, asymptomatic transaminitis
• 2-6d: severe gastroenteritis, hepatic failure and pancreatitis

Erythromelagia

• acromelic acids
• 24-72h onset, with resolution over 8 days to 5 months: burning pain, redness and swelling of hands and feet, exacerbated by heat and cold

VERY LATE ONSET (>24 HOURS)

Nephrotoxic, e.g. Cortinarius  and A. smithiana spp

• orellanine-mediated
• 24-36h: headache, GI symptoms, flank pain progressing to interstitial nephritis and renal failure

Rhabdomyolysis, e.g. tricholoma and Russula  spp

• onset 24-72h: fatigue, myalgias, muscle weakness and myocarditis (very rare)

ASSESSMENT

History

• Exposure history
  • Description of the mushroom (e.g. color, texture, cap appearance)
  • How much was eaten?
  • Recent alcohol intake? (f suspected disulfram-like reaction)
  • Location and season of mushroom collection/ purchase?
  • How was mushroom collected, prepared, and stored?
  • Anyone else exposed or ill?
• Symptom history
  • features of toxicity syndromes describe above
  • Time course (onset and duration after mushroom exposure)

Examination

• Often non-specific
• Assess for:
  • Dehydration secondary to gastroenteritis
  • Specific toxidromes (e.g. cholinergic)
  • Features of organ failure (e.g. hepatic encephalopathy)

Investigations

• guided by clinical assessment
• check LFTs and renal function first if GI symptoms present >6 hours after exposure
• consider: FBC, UEC, CMP, LFTs, coagulation profile, CK, glucose, ECG, blood gas and lactate
• mycologist examination of mushroom samples

MANAGEMENT

Resuscitation

• rarely necessary
• life-threats include:
  • severe gastroenteritis causing hypovolemic shock
  • seizures or coma
  • cholinergic crisis
  • complications of organ failure (e.g. hepatic toxicity, renal toxicity)

Supportive care and monitoring, may include:

• neurological observations for seizures, coma and paralysis
• delirium management
• glucose monitoring
• cardiac monitoring
• rehydration and antiemetics
• monitor LFTs for 48 hours if suspected cyclopeptide hepatotoxin

Decontamination

• activated charcoal 50g (1g/kg in children) if onset of GI symptoms occurs >6 hours post-ingestion

Enhanced elimination

• consider multi-dose activated charcoal if suspected cyclopeptide hepatoxicity as alpha-amantin undergoes enterohepatic circulation

Antidotes

• cyclopeptide hepatoxicity (e.g. GI symptoms onset >6 hours or increasing transaminases)
  • N-acetylcysteine
  • penicilin 1 MU/kg/day
  • silibinin 5 mg/kg IB over 1 hour then 20 mg/kg/day for up to 3 days
• cholinergic syndrome
  • atropine
• seizures due to Gyromitra  mushrooms
  • pyridoxine (similar management to isonizid toxicity)

Disposition

• discharge home if risk assessment does not predict severe toxicity and:
  • asymptomatic, or
  • early onset GI symptoms are resolving and patient is clinically well (check LFTs and renal function first if lasts >6 hours)
• observe in hospital:
  • significant symptoms
  • risk assessment predicts potential for severe toxicity
• admit to HDU/ ICU:
  • coma or CNS dysfunction
  • liver or renal failure (may require transfer to a specialist center)

PROGNOSIS

• Most mushroom toxicity presentations are mild or resolve with supportive care
• mushroom ingestions which present with gastrointestinal symptoms will recover without complication when provided adequate supportive care.
• Nephrotoxicity from Cortinarius ingestion may lead to a requirement for haemodialysis (51%), end-stage renal failure (11%) and require renal transplantation (Danel et al, 2001).
• Neurotoxicity from Gyromitra typically resolves over a week with effective seizure management, though fatalities can occur .
• A small minority of patients who ingest Amanita mushrooms develop hepatoxicity (~1%). However, about half of those who present with acute liver failure may require liver transplantation. (Karvellas et al, 2016)
• Anticholinergic toxicity usually resolves without sequelae, however deaths have occurred (Pauli and Foote, 2005)

PREVENTION

• Don’t collect and eat wild mushrooms!

OTHER

• The Emperor Claudius is thought to have been murdered by his wife Agrippina with the aid of poisonous mushrooms.
• The German composer Johan Schubert died from poisonous mushrooms but remained adamant they were edible until the end.

References and Links

• Bedry R, Baudrimont I, Deffieux G, Creppy EE, Pomies JP, Ragnaud JM, Dupon M, Neau D, Gabinski C, De Witte S, Chapalain JC, Godeau P, Beylot J. Wild-mushroom intoxication as a cause of rhabdomyolysis. N Engl J Med. 2001 Sep 13;345(11):798-802. PMID: 11556299.
• Danel VC, Saviuc PF, Garon D. Main features of Cortinarius spp. poisoning: a literature review. Toxicon. 2001 Jul;39(7):1053-60. doi: 10.1016/s0041-0101(00)00248-8. PMID: 11223095.
• Diaz JH. Syndromic diagnosis and management of confirmed mushroom poisonings. Crit Care Med. 2005 Feb;33(2):427-36. PMID: 15699849.
• Gawlikowski T, Romek M, Satora L. Edible mushroom-related poisoning: A study on circumstances of mushroom collection, transport, and storage. Hum Exp Toxicol. 2015 Jul;34(7):718-24. doi: 10.1177/0960327114557901. Epub 2014 Nov 4. PMID: 25378095.
• 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. doi: 10.1111/liv.13080. Epub 2016 Mar 4. PMID: 26837055.
• Lima AD, Costa Fortes R, Carvalho Garbi Novaes MR, Percário S. Poisonous mushrooms: a review of the most common intoxications. Nutr Hosp. 2012 Mar-Apr;27(2):402-8. PMID: 22732961.
• Pauli JL, Foot CL. Fatal muscarinic syndrome after eating wild mushrooms. Med J Aust. 2005 Mar 21;182(6):294-5. doi: 10.5694/j.1326-5377.2005.tb06705.x. PMID: 15777146.
• Roberts DM, Hall MJ, Falkland MM, Strasser SI, Buckley NA. Amanita phalloides poisoning and treatment with silibinin in the Australian Capital Territory and New South Wales. Med J Aust. 2013 Jan 21;198(1):43-7. PMID: 23330770.