Mushroom poisoning

Background

• Mushroom poisoning encompasses a spectrum of clinical syndromes caused by ingestion of toxic mushroom species.
• The key distinction for the emergency physician is between early-onset (<6 hours) and delayed-onset (>6 hours) symptoms, as delayed presentations are far more likely to be life-threatening.
• There are over 5,000 species of mushrooms; approximately 50-100 are toxic to humans
• 95% of mushroom-related deaths worldwide are caused by amatoxin-containing mushrooms (Amanita, Galerina, Lepiota species)
• Most poisonings occur in foragers who misidentify wild mushrooms as edible species
  • Immigrants may mistake toxic local species for edible ones from their home country
  • Recreational users may confuse toxic species for hallucinogenic Psilocybe mushrooms
• Children and elderly are more susceptible to volume depletion and toxicity
• Amatoxins are heat-stable — cooking does not eliminate the toxin
• Most mushroom ingestions are benign GI irritants; the challenge is identifying the dangerous minority

Critical clinical pearl

• Symptom onset >6 hours after ingestion should be considered potentially lethal until proven otherwise
• Early-onset GI symptoms (<6 hours) are generally self-limited
• Delayed-onset GI symptoms (6-24+ hours) suggest amatoxin, gyromitrin, or orellanine poisoning and carry significant morbidity and mortality

Clinical features

Classified by onset and predominant toxidrome:

Early-onset syndromes (<6 hours)

GI irritant syndrome (most common)

• Caused by many species (e.g. Chlorophyllum molybdites, Entoloma, Boletus)
• Nausea, vomiting, abdominal cramps, diarrhea within 1-3 hours
• Self-limited; resolves with supportive care
• Rarely life-threatening unless severe dehydration

Muscarinic (cholinergic) syndrome

• Caused by Inocybe and Clitocybe species
• Onset 15-30 minutes
• SLUDGE/DUMBELS: salivation, lacrimation, urination, diarrhea, GI cramping, emesis; diaphoresis, urination, miosis, bronchospasm/bronchorrhea, emesis, lacrimation, salivation
• Bradycardia, hypotension
• Treatment: atropine

Isoxazole (anticholinergic/GABAergic) syndrome

• Caused by Amanita muscaria (fly agaric), A. pantherina
• Onset 30 min - 2 hours
• Confusion, agitation, hallucinations, ataxia, myoclonus, seizures
• Mydriasis, tachycardia, dry skin
• Alternating sedation and excitation
• No hepatic or renal injury
• Treatment: supportive; benzodiazepines for agitation/seizures

Psilocybin syndrome

• Caused by Psilocybe, Panaeolus, Gymnopilus species
• Onset 30 min - 1 hour
• Hallucinations (visual), euphoria, anxiety, agitation, tachycardia, mydriasis, hyperthermia
• Self-limited (4-6 hours)
• Treatment: supportive; benzodiazepines for agitation; reassurance

Coprine (disulfiram-like) syndrome

• Caused by Coprinus atramentarius (inky cap)
• Symptoms occur only when mushroom ingestion is combined with alcohol (within 2-72 hours of mushroom ingestion)
• Flushing, tachycardia, headache, nausea, vomiting, hypotension
• Treatment: supportive; IV fluids; avoid alcohol; fomepizole may be considered in severe cases

GI with early renal toxicity

• Caused by Amanita smithiana
• GI symptoms as early as 2-4 hours; renal injury follows
• May present earlier than other serious syndromes — do not assume safety based on early onset alone

Delayed-onset syndromes (>6 hours) — potentially life-threatening

Amatoxin syndrome (most dangerous)

• Caused by Amanita phalloides (death cap), A. virosa (destroying angel), A. verna, A. bisporigera, Galerina spp., Lepiota spp.
• Phase 1 (6-24 hours): severe cholera-like vomiting and watery diarrhea → dehydration, electrolyte derangement
• Phase 2 (24-48 hours): apparent clinical improvement ("false recovery" or "quiescent phase") — transaminases begin rising
• Phase 3 (48-96 hours): fulminant hepatic failure — markedly elevated AST/ALT, coagulopathy, hypoglycemia, encephalopathy, hepatorenal syndrome, DIC, multiorgan failure, death
• Mortality 10-30% overall; higher in children and delayed presentations
• Mechanism: alpha-amanitin inhibits RNA polymerase II → arrests protein synthesis → hepatocellular necrosis
• Amatoxin undergoes enterohepatic recirculation, which is the rationale for multi-dose activated charcoal

Gyromitrin syndrome

• Caused by Gyromitra esculenta (false morel) and related species
• Onset 6-12 hours
• GI symptoms followed by hepatic failure (similar to amatoxin)
• Also causes methemoglobinemia, hemolysis, seizures (via GABA inhibition)
• Mechanism: gyromitrin metabolized to monomethylhydrazine (rocket fuel analog)
• Treatment: pyridoxine (vitamin B6) 25 mg/kg IV for seizures refractory to benzodiazepines; folinic acid; methylene blue for methemoglobinemia

Orellanine syndrome

• Caused by Cortinarius species
• Onset delayed 1-3 days, sometimes up to 2 weeks
• GI symptoms followed by progressive renal failure
• Renal injury may be irreversible, requiring long-term hemodialysis or transplant
• No specific antidote; supportive care

Norleucine (allenic norleucine) syndrome

• Caused by Amanita smithiana, A. proxima
• Onset 4-12 hours (may overlap with early-onset range)
• GI symptoms followed by renal failure (typically reversible)
• Mild hepatotoxicity may accompany

Differential diagnosis

Other causes of acute gastroenteritis

• Acute gastroenteritis (viral, bacterial)
• C. difficile

Other causes of acute liver failure

• Acetaminophen toxicity
• Viral hepatitis
• Wilson disease
• Other drug-induced liver injury

Other toxic ingestions

• Iron toxicity
• Copper sulfate toxicity
• Caustic ingestion
• Organophosphate toxicity (for muscarinic symptoms)

Mushroom toxicity by Type

Mushroom	Toxin	Pathologic Effect
Amanita	Amatoxin	Hepatotoxicity
	Coprine	Disulfiram-like
Crotinarius	Orellanine	Delayed renal failure
Gyromitra	Gyromitrin	Seizures
	Ibotenic Acid	Anticholinergic
	Muscarine	Cholinergic
	Orellanin	Nephrotoxicity
	Psilocybin	Hallucinations

Evaluation

Workup

• Detailed history is the most critical diagnostic tool:
  • Timing of symptom onset relative to ingestion (early vs. delayed)
  • Type of mushroom (save specimens if available; photograph; consult mycologist)
  • Geographic location and season of foraging
  • Preparation method (raw, cooked)
  • Number of people who shared the meal and their symptoms
  • Co-ingestion (especially alcohol for coprine syndrome)
• Attempt mushroom identification:
  • Save any remaining mushroom specimens (including spore prints)
  • Contact local Poison control center — may have access to mycologists
  • Telemedicine/photograph-based identification resources
• Labs (for all symptomatic patients):
  • CBC, BMP, hepatic function panel (AST, ALT, total bilirubin, albumin), coagulation studies (PT/INR), lipase
  • Blood glucose (hypoglycemia may signal hepatic failure)
  • Urinalysis
  • Lactate
• Additional labs for suspected amatoxin or serious poisoning:
  • Serial LFTs and coagulation studies every 6-12 hours for at least 48-72 hours (transaminases may be initially normal during Phase 1)
  • Ammonia (for hepatic encephalopathy)
  • Blood type and screen (anticipate possible liver transplant)
  • Urine amatoxin assay — available at some specialty/reference labs; may be positive within 24-48 hours of ingestion; not widely available or rapid enough to guide acute management
• Additional labs for specific syndromes:
  • Methemoglobin level (gyromitrin poisoning)
  • CK (rhabdomyolysis)
  • Serial creatinine (orellanine, norleucine syndromes)
• Salicylate, acetaminophen, ethanol levels — if intentional ingestion suspected

Diagnosis

• Primarily clinical, based on timing of symptom onset and symptom constellation
• Key diagnostic rule: GI symptoms >6 hours post-ingestion = assume amatoxin poisoning until proven otherwise
• Rising AST/ALT after initial GI illness is highly concerning for amatoxin or gyromitrin hepatotoxicity
• The "false recovery" period in amatoxin poisoning (GI symptoms improve before liver failure manifests) is a dangerous diagnostic trap — do not discharge patients during this window

Management

All patients

• IV fluid resuscitation; correct electrolyte abnormalities and hypoglycemia
• Continuous cardiac monitoring
• Contact Poison control and attempt mushroom identification
• Anti-emetics (ondansetron) for persistent vomiting

GI decontamination

• Activated charcoal (1 g/kg, max 50 g) if presenting within 1-2 hours of ingestion
• For suspected amatoxin poisoning: give multi-dose activated charcoal (even if presenting late) to interrupt enterohepatic recirculation
  • Repeat dosing every 2-4 hours
• Gastric lavage generally not recommended beyond 1 hour post-ingestion
• Whole-bowel irrigation may be considered for amatoxin ingestion

Amatoxin-specific management

No proven antidote exists; all therapies are supportive and based on limited evidence:

• N-acetylcysteine (NAC): IV per acetaminophen protocol — provides glutathione, hepatoprotective; widely recommended
• Silibinin (IV): 5 mg/kg IV over 1 hour, then 20 mg/kg/day as continuous infusion — thought to block hepatic amatoxin uptake; used in Europe; not FDA-approved in the US
  • Silymarin (oral): milk thistle extract, 1 g PO QID — available over-the-counter in North America as surrogate for IV silibinin
• High-dose penicillin G: 300,000-1,000,000 units/kg/day IV (commonly 4 million units q4h) — may compete with hepatic uptake of amatoxin; evidence is limited
• Multi-dose activated charcoal — interrupts enterohepatic recirculation (see above)
• Aggressive fluid resuscitation — maintain urine output to enhance renal amatoxin clearance
• Liver transplant evaluation: early referral to a transplant center for patients with progressive hepatic failure
  • King's College criteria or Clichy criteria may guide transplant listing
  • Approximately 50% of patients who develop fulminant hepatic failure will require transplantation

Gyromitrin-specific management

• Pyridoxine (vitamin B6): 25 mg/kg IV — for seizures refractory to benzodiazepines (gyromitrin depletes pyridoxal phosphate/GABA)
• Folinic acid — adjunctive (hydrazines inhibit folic acid conversion)
• Methylene blue 1-2 mg/kg IV — for methemoglobinemia
• Supportive care for hepatic failure similar to amatoxin poisoning

Muscarinic syndrome management

• Atropine 0.5-1 mg IV (adults), 0.01-0.02 mg/kg IV (children); titrate to effect (drying of secretions, resolution of bradycardia)
• May need repeated dosing

Isoxazole/psilocybin syndrome management

• Supportive care
• Benzodiazepines for agitation, anxiety, or seizures
• Reassurance and calm environment (especially psilocybin)
• Avoid restraints if possible (risk of rhabdomyolysis with agitation)

Orellanine syndrome management

• No specific antidote
• Supportive care with nephrology consultation
• Hemodialysis for renal failure; renal transplant if no recovery

Disposition

• Early-onset GI symptoms only (<6 hours), known non-toxic species, mild symptoms:
  • Observe 4-6 hours; if tolerating PO and clinically well, may discharge with return precautions
• Symptom onset >6 hours post-ingestion, unknown mushroom species, or suspected amatoxin:
  • Admit all patients — ICU if hemodynamically unstable or evidence of organ injury
  • Serial labs (LFTs, coagulation, renal function, glucose) every 6-12 hours for minimum 48-72 hours
  • Do NOT discharge during the "false recovery" phase (24-48 hours post-ingestion when GI symptoms improve but hepatic injury is evolving)
  • Early contact with liver transplant center for amatoxin poisoning
• Patients with isoxazole/psilocybin syndromes:
  • Observe until symptoms resolve (typically 4-8 hours); discharge if stable and safe
  • Psychiatric evaluation if intentional ingestion
• Orellanine suspected:
  • Admit; serial renal function monitoring; nephrology consultation
• All intentional ingestions: psychiatric evaluation mandatory prior to discharge
• All patients: contact Poison control (1-800-222-1222 in the US)

See Also

• Acute liver failure
• Acetaminophen toxicity
• Methemoglobinemia
• Organophosphate toxicity
• Caustic ingestion
• Copper sulfate toxicity
• Rhabdomyolysis
• Acute kidney injury

External Links

• StatPearls — Amatoxin Mushroom Toxicity
• Medscape — Mushroom Toxicity
• American Association of Poison Control Centers (1-800-222-1222)
• Diaz JH — Amatoxin-Containing Mushroom Poisonings: Species, Toxidromes, Treatments, and Outcomes (2018)