Mushrooms

Elora Apantaku, MD
Epidemiology
● Rare, but consistent, annual
exposures
● 0.25% of Poison Center
Calls
● 5/100,000 persons per year
will have a toxic mushroom
exposure
● 100,000 mushrooms species
exist
● < 0.1% of these are toxic
● 75-95% of exposures have an
unidentified mushroom spp.
● Most common symptoms are
GI.
Classification
● Because classification is difficult by species identification,
classification by clinical symptoms is recommended.
○ However, many mushrooms present with mixed symptoms
● Additional attempts at identification involve:
○ Geographic Origin
○ Initial Signs and Symptoms
○ Organ System(s) Involved
○ Obtaining a sample/photograph/spores
○ Contact a mycologist
Management and Disposition
● Activated charcoal is recommended if a potentially toxic mushroom is ingested.
● Fluids, electrolytes, and dextrose repletion PRN.
● Early GI symptoms (<5 hours) that remain for several hours despite supportive care
should be admitted.
● Patients with delayed initial symptoms (>5 hours) suggestive of amatoxin exposure
should be hospitalized.
● Certain mushrooms have nephrotoxicity and hepatotoxicity days to weeks after
ingestion. Subsequent follow-up is encouraged.
I: Galerinas, Lepiotas, and (some) Amanitas
● 50 - 100 cases reported ● α-Amanitin
annually, much fewer in ○ Most toxic cyclopeptide
North America ○ Cause Liver, kidney, and CNS
○ Most North American damage
cases occur along West ○ Rapidly absorbed from GI tract, liver
and East Coasts uptake by bile acid transporters
● Initial presentation of ○ Interferes with RNA polymerase II,
n/v/d, with more severe prevents protein synthesis →
presentation later apoptosis
● Early amanitas look like ○ Heat stable, unaffected by cooking
edible puffball mushrooms ○ Amanitin Lethality is 0.1mg/kg
■ 15 mg/1 g dry Amanitas
phalloides (0.5 g lethality)
■ 3.5 mg/1 g dry Lepiotas
(2 g lethality)
Early Amanita virosiformis
I: Galerinas, Lepiotas, and (some) Amanitas
Clinical Presentation
● Phase III: 2 - 6 days post ingestion
● Phase I: 5 - 24 hrs post ingestion
○ severe gastroenteritis
● Phase II: 12 - 36 hrs post ingestion
○ Transient improvement of
symptoms with worsening hepatic
injury
■ Acute liver failure INR > 1.5
■ May continue to have n/v/d,
abd pain
○ Clinically apparent hepatotoxicity
■ Elevated bilirubin, AST, ALT,
jaundice, and hypoglycemia
■ Additional endocrine
abnormalities, including
elevated insulin and c-
peptide concentrations from
β cell toxicity
I: Galerinas, Lepiotas, and (some) Amanitas
Treatment
● Emesis, lavage,
● N-acetylcysteine for hepatoprotection, standard non-
catharsis,
hemodialysis, &
acetaminophen dosing.
hemoperfusion ● Polymyxin B has chemical similarities to α-amanitin and
can be competes with similar binding sites. Dosing 0.75 mg/kg.
considered ● Silibinin (a milk thistle extract) competitively inhibits the
during the first enterohepatic recycling of α-amanitin and may (or may not be) undergoing
12 to 24 hours clinical trials to assess effectiveness. Dosing 20-50 mg/kg/d.
following
ingestion
I: Galerinas, Lepiotas, and (some) Amanitas
Time of Primary
Xenobiotics Site of Clinical Findings Mortality Therapy
Onset
Toxicity

Cyclopeptides: 5-24 Liver Phase I 30% Early: Activated Charcoal

1. Amatoxins hours GI toxicity, n/v/d Hemoperfusion
2. Phallotoxins Hemodialysis
Phase II
Quiescent Silibinin

Phase III Polymyxin B

n/v/d, jaundice,
elevated AST, Late: N-acetylcysteine
ALT, bilirubin
 I: Galerinas, Lepiotas, and (some) Amanitas

Galerina marginata Lepiota subincarnata Amanita virosiformis

“Funeral bell” & “Deadly skullcap” Grows in dead plant material “Narrow-Spored Destroying Angel”
Predominantly grows on decaying trees and occasionally on lawns Grows in Oak forests
II: Gyomitras
● Confused for edible morels, in spring,
under conifers.
● Contains gyromitrin, hydrolyzed several
times to monomethylhydrazine, which
interferes with pyridoxal phosphate
synthesis, impairing the production of
GABA and causing neurologic
symptoms.
● Toxicity within 5 - 10 hrs post ingestion
○ Symptoms: n/v/d, abd pain,
headaches, weakness, diffuse
muscle cramping
○ Rarely: nystagmus, ataxia,
delirium, stupor, seizures, and
Treatment
coma.
● Activated charcoal 1g/kg
○ Most patients improve within ● Benzodiazepines for seizures
several days. ● Pyridoxine 70 mg/kg IV (max 5g)
II: Gyomitras
Time of Primary
Xenobiotics Site of Clinical Findings Mortality Therapy
Onset
Toxicity

Gyromitrin 5-10 CNS Seizures, rare Benzodiazepines

hydrolyzed into hours abdominal pain,
monomethyl- n/v, Pyridoxine 70 mg/kg
hydrazine weakness, (max 5 g)
hepatorenal
failure
III: Muscarine-Containing Mushrooms
Clinical Presentation
● Cholinergic symptoms:
○ bradycardia, miosis, salivation, lacrimation, vomiting,
diarrhea, bronchospasm, bronchorrhea, and micturition.
● Timing:
○ Onset within 0.25 - 2hrs, complete resolution within 24 hrs
● Treatment: Clitocybe dealbata
○ IV Atropine for symptomatic bradycardia
○ (1-2 mg slowly via IV (adults) or 0.02 mg/kg IV (children))
for symptomatic bradycardia.

Omphalotus illudens
III: Muscarine-Containing Mushrooms
Time of Primary Site of
Xenobiotics Onset Toxicity Clinical Findings Mortality Therapy

Muscarine 0.25 - 2 Autonomic salivation, rare Adults:

hours Nervous bradycardia, Atropine 1-2 mg IV
System lacrimation,
urination, Children:
defecation, Atropine 0.02 mg/kg IV
diaphoresis (minimum 0.1 mg)
IV: Coprine-Containing Mushrooms
● “Inky” gills
● Edible, but poisonous when consumed with alcohol
● Coprine is hydrolyzed into 1-aminocyclopropranol
then metabolized to cyclopropanone hydrate, which
inhibits aldehyde dehydrogenase
● Sprouts following rains, found commonly in
disturbed, urban areas such as vacant lots and lawns

Coprinopsis atramentaria
Coprine “Tippler’s Bane”
IV: Coprine-Containing Mushrooms
Time of Primary Site of
Xenobiotics Onset Toxicity Clinical Findings Mortality Therapy

Coprine 0.5 - 2 Aldehyde Disulfiramlike rare Antiemetics

hydrolyzed to hours dehydrogenase effect with
1-aminocyclopropanol ethanol: Fluid Resuscitation
and cyclopropanone tachycardia,
hydrate nausea, Fomepizole for
vomiting, refractory toxicity
flushing
V: Ibotenic Acid- and Muscimol-Containing Mushrooms

● Found in Woodlands
● Ibotenic acid is a glutamate antagonist at NMDA
receptors and causes myoclonic movements and
seizures.
● Muscimol is a GABA type A agonist and causes
hallucinations, somnolence, and dizziness.

Amanita muscaria
Muscimol “Fly amanita”

Ibotenic Acid
V: Ibotenic Acid- and Muscimol-Containing Mushrooms
Time of Primary Site of
Xenobiotics Onset Toxicity Clinical Findings Mortality Therapy

Ibotenic Acid 0.5 - 2 CNS GABAergic rare Benzodiazepines

and its active metabolite hours effects, rare during excitatory
Muscimol delirium, phase
hallucinations,
dizziness, ataxia
VI: Psilocybin-Containing Mushrooms
● Popular recreational drug, grown throughout the US.
● Psilocybin is rapidly and completely hydrolyzed to
psilocin which is almost identical structurally to
serotonin, and is thought to function as an agonist.
● Symptoms include ataxia, hyperkinesis, visual illusions,
and hallucinations.
Psilocybe cubensis
● May also cause GI distress, tachycardia, anxiety, tremor,
and agitation (rare cases of kidney failure, seizures, and
cardiopulmonary arrest may be 2/2 coingestions).

Serotonin
(for comparison)

Psilocybin Psilocin
VI: Psilocybin-Containing Mushrooms
Time of Primary Site of
Xenobiotics Onset Toxicity Clinical Findings Mortality Therapy

Psilocybin 0.5 - 1 CNS Ataxia, rare Benzodiazepines

hours hyperkinesis, for agitation
Psilocin hallucinations,
illusions,
n/v
VII: Gastrointestinal Toxin-Containing Mushrooms

● Literally 100s of mushrooms

● Toxicity thought to occur due to malabsorption of of proteins and sugars,
ingestion of infected mushrooms, or allergies
● Resolution of symptoms within 24 hours (if symptoms persist, consider
coingestion)

Xenobiotics Time of Primary Site of Clinical Findings Mortality Therapy

Onset Toxicity

Various 0.3 - 3 GI n/v/d, rare Symptomatic Care

GI hours malaise
Irritants
VIII: Orellanine- and Orellinine-containing Mushrooms

● Toxicity is from Orellanine, a nephrotoxin activated by cytochromes.

● Initial manifestations include headache, n/v/d, chills, polydipsia,
anorexia, oliguria, flank and abdominal pain 24 to 72 hours after
ingestion.
● Kidney failure takes days to weeks to develop (3-21 d), but can be
proceeded by hematuria, pyuria, and proteinuria.
Cortinarius rubellus
“Deadly webcap”

Orellanine
VIII: Orellanine- and Orellinine-containing Mushrooms
Time of Primary Site of
Xenobiotics Onset Toxicity Clinical Findings Mortality Therapy

Orellanine > 1 day Kidney Phase I: n/v rare Hemodialysis for

Orellinine - weeks Acute Kidney Injury
Phase II:
Oliguria, Acute
Kidney Injury
IX: Allenic Norleucine-Containing Mushrooms

● Confusion with edible pine mushroom matsutake. Allenic Norleucine

● GI symptoms initially are followed by kidney injury after several
days, which can manifest as oliguria or anuria.
● Mechanism of toxicity is unknown, but isolated allenic
Amanita Smithiana
norleucine had cytotoxic effects on renal tubular cells.

Xenobiotics Time of Primary Site of Clinical Findings Mortality Therapy

Onset Toxicity

Allenic norleucine 0.5 - 12 Kidney Phase I: n/v None Hemodialysis for

hours Acute Kidney Injury
Phase II:
Oliguria, Acute
Kidney Injury,
Anuria
X: Cycloprop-2-Enecarboxylic Acid-Containing Mushrooms

● Although considered edible in Europe, Tricholoma

equestre ingestions can cause significant skeletal
muscle myotoxicity.
● Case study in Poland and France
○ Fatigue, muscle weakness, and myalgias in 24 to 72
hrs
○ Flushing, nausea without vomiting, profuse sweating Tricholoma equestre
○ Elevated Creatinine Phosphokinase (CPK) “Man on Horseback”
○ EMG & biopsies showed myofibrillar injury and edema
○ Dyspnea, muscle weakness, acute myocarditis,
dysrhythmias, CHF → death

Russula subnigricans
“Nisekurohatsu”
X: Cycloprop-2-Enecarboxylic Acid-Containing Mushrooms
Time of Primary Site of
Xenobiotics Onset Toxicity Clinical Findings Mortality Therapy

Cycloprop-2- 24 - 72 Muscle Fatigue, nausea, 10% Sodium bicarbonate

enecarboxylic acid hrs (skeletal & vomiting,
cardiac) muscle Hemodialysis for
0.5-2 weakness, Acute Kidney Injury
hrs myalgias,
increased CK,
flushing,
diaphoresis,
myocarditis
XI: 2R-Amino-4,5-Hydroxy-5-Hexynoic Acid and 2R-Amino-
5-Hexynoic Acid-Containing Mushrooms
● Cause of toxic effects are toxic amino acids
● Myocarditis and sudden cardiovascular collapse
● Thought to be the most likely cause of Yunnan
Sudden Unexplained Death in the Yunnan
province of China
○ Deaths following exposure (likely 2/2
Trogia venenata
ventricular fibrillation) “Little white mushroom”
● Symptoms include myalgias, dysesthesias, and
tremor.
● Hypotension and syncope occur after several
days.
XI: 2R-Amino-4,5-Hydroxy-5-Hexynoic Acid and 2R-Amino-5-Hexynoic Acid-Containing Mushrooms

Time of Primary Site of

Xenobiotics Onset Toxicity Clinical Findings Mortality Therapy

2R-Amino-4,5- 1-5 Cardiac and Tachycardia, GI High? ICU monitoring

Hydroxy-5-Hexynoic days Skeletal symptoms,
Acid and 2R-Amino-5- Muscle myalgias,
Hexynoic Acid- tremor, seizures,
Containing dizziness,
Mushrooms weakness,
syncope,
palpitations,
VFib
XII: Acromelic Acid-Containing Mushrooms

● Acromelic acids acts as an NMDA receptor

agonist.
● Erythromelalgia - paresthesias of distal
extremities followed by paroxysms of severe
Acromelic Acid
burning dysesthesias. Resolves after several
months. Clitocybe acromelalga

Xenobiotics Time of Primary Site of Clinical Findings Mortality Therapy

Onset Toxicity

Acromelic acids 24 Peripheral Erythromelagia, None Symptomatic Care

hours Nervous erythema,
System edema
XIII: Polyporic Acid-Containing Mushrooms

● Encephalopathy
● CNS symptoms: vertigo, ataxia, visual
disturbances, somnolence

Hapalopilus nidulans
“Cinnamon bracket”

Pleurocybella porrigens
“Angel wings”

Polyporic acid
XIII: Polyporic Acid-Containing Mushrooms
Xenobiotics Time of Primary Site of Clinical Findings Mortality Therapy
Onset Toxicity

Unknown 1 - 31 CNS Encephalopathy, High Hemodialysis

(Pleurocybella days convulsions, (30%)
porrigens) myoclonus in
patients with
CKD

Polyporic acid > 12 GI, CNS n/v, abdominal None Symptomatic care
(Hapalopilus rutilans) hours pain, vertigo,
ataxia,
drowsiness,
encephalopathy
XIV: Involutin-Containing Mushrooms
Involutin
● Immune-mediated hemolytic anemia, hemoglobinuria, oliguria, and
AKI.
● IgG antibodies to involutin have been detected in affected patients.

Paxillus involutus
“Brown roll-rim”

Time of Primary Site of

Xenobiotics Clinical Findings Mortality Therapy
Onset Toxicity

Involutin Repeat RBCs, Kidney Hemolytic rare Hemodialysis

exposure, anemia, AKI
0.5 - 3
hours
XV: Lycoperdonosis

● Puffball mushrooms (multiple

Lycoperdon spp.) are edible but
release spores when compressed
or agitated.
● Lycoperdonosis, a hypersensitivity
pneumonitis, can occur within Lycoperdon perlatum
hours after massive spore “Common puffball”

exposure.

Xenobiotics Time of Primary Site of Clinical Findings Mortality Therapy

Onset Toxicity

Spores Hours Pulmonary, GI Cough, SOB, None Corticosteroids

fever, n/v