Transcript Mushrooms, Mycology and Toxicology

Mushrooms, Mycology
and Toxicology
Tracy A. Cushing, MD MPH
University of Colorado School of
Medicine
1
Epidemiology
 <0.5%
of all toxic
exposures over 19
years (AAPCC)
 Estimated 5
exposures per
100,000 pop.
 95% of exposures
are unidentified
 22
deaths in 19 years
of AAPCC data
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Mushroom Life Cycle
Spore
Spore Germination
Mature
Mushroom
Mycelium
Mushroom Primordia
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Mushroom Anatomy
 Cap
(pleus)
 Scales
 Ring (annulus)
 Cup (volva)
 Gills (Lamellae)
 Stem (stape)
 Mycelial threads
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Classification

1.
2.
3.
4.
5.
10 main toxins:
General GI irritants
Cyclopeptides
Gyromitrin
Muscarine
Coprine
6. Ibotenic acid &
muscimol
7. Psilocybin
8. Orellanine
9. Allenic norleucine
10. Myotoxins
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Classification
 Onset
of symptoms…….
Early (0-4)
Late (>6 hrs)
Cyclopeptides
GI toxins
Ibotenic acid/muscimol
Psilocybin
Muscarine
Coprine
Gyromitrin
Orelline/orellanine
Allenic norleucine
Myotoxin
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….and target organ system

CNS

Hepatic

Renal

Muscle

PNS
Amatoxins
-Amanita
-Galerina
-Lepiota
Ibotenic acid/muscimol
Psilocybin
Gyromitrin
Orellanine
Allenic norleucine
“Myotoxin” (Tricholoma)
Muscarine
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I. Gastrointestinal Toxins
 Nausea,
vomiting, abdominal cramping,
diarrhea
 Onset within 1-2 hours of ingestion**
 Watery/loose stools
 Symptom remission in 8-12 hours
 Supportive care
(IVF, antiemetics, loperamide
as needed).
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GI-toxic Species

Chlorophyllum molybdites

-summer, white, large, free gills

Omphalotus illudens

-bright orange/yellow, grows in clusters along
stumps/roots
-sharp-edged gills


Amanaita flavorubescens/ Amanita
brunnesce

-broad yellow-brown caps
-stalks enlarge towards base

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II. Isoxazole-derived Toxins
 Ibotenic
acid ------------> glutamic acid
 Muscimol------------> GABA
 Onset
30-120 minutes
 Ataxia, somnolence, delirium, hallucinations
 Children: hyperactivity, hyperreflexia,
seizures
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Amanita muscaria
Amanita pantherina
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III. Coprine Toxins

Glutamine-derived toxin
 Inhibits acetaldehyde dehydrogenase

Symptom onset within 15-30 min of alcohol
ingestion
 Severe headache, flushing, tachycardia,
hyperventilation, palpitations
 EtOH sensitivity lasts 2-72 hours

Supportive treatment, no role for AC
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 Coprinus
atramentarius
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IV. Muscarine

Onset 30-60 min
 Salivation, urination,
lacrimation, diarrhea,
diaphoresis, abdominal
pain, vomiting
(SLUDGE)
 Bradycardia,
bronchospasm
 Miosis
Treatment:
 Supportive care
 Atropine for bradycardia,
excessive secretions
(1 mg IV adults/0.01 mg/kg
IM or IV kids)
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Clitocybe, Inocybe
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V. Psilocybin & psilocin
“Magic Mushrooms”
Plentiful in North America
Structurally similar to serotonin  5HT(2)
30-60 min: ataxia, hyperkinesis, visual
hallucinations.
may develop anxiety, agitation, tremors, seizures.
Resolution in 6-12 hours.
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Psilocybe cubensis
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Late-onset Toxins
 Usually
more severe / serious
 May be hours – days after ingestion
 Liver, Kidneys, Muscle
 History
Cyclopeptide
Orellanine/orelline
Gyromitrin
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A. Cylopeptide Toxins
Most toxic: “amatoxin”
 Limited protein binding,
found in Amanita
low
plasma
concentration
phalloides; A.
tenuifoilia; A. virosa.
 ++ Enterohepatic
circulation
 -Galeria autumnalis;
G.marginata, G.
 LD50= 0.1 mg /kg
venenata


Lepiota josserandi; L.
helveola

1.5-2.5 mg amanitin in 1
gm A.phalloides
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Amanita Phalloides
“Death Angel”
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Galeria
autumnalis
Lepiota josserandi
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Clinical Presentation
I – gastroenteritis, diarrhea (5-24 hrs)
 Stage II – transient improvement (12-36 hrs)
 Stage III – hepatic failure; renal failure; death
(2-6 DAYS)
 Stage
 Amatoxin inhibits
RNA polymerase II - no
transcription
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Treatment

Supportive, ABC’s
Fluids / electrolytes / glucose
Thiocytic Acid (?)
Penicillin G (1 gm/kg/d) (?)
Silibinin (milk thistle) (?)
Cimetidine
NAC - encephalopathy
Liver Transplantation (1983)

10-20% mortality (higher in kids)







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B. Gyromitrin
 Gyromitra
species
 Inhibits GABA by interfering with pyridoxine
 Europe > North America
 Onset 5-10 hours
 Headache, weakness, nausea, vomiting,
cramping, delirium, seizures
 Rarely progresses to coma, hepatorenal
failure, or death
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Treatment
 Supportive
 Activated
charcoal
 Benzodiazepines
 Pyridoxine 70 mg/kg IV for intractable
seizures
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Gyromitra sp. (false morel)
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C. Orellanine & orelline
 Onset
24-36 hrs (delayed GI toxicity)
 HA, chills, myalgias, nausea, vomiting,
abdominal/flank pain
 Oliguric renal failure (days-weeks)
 Hematuria, leukocyturia, proteinuria
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Cortinarius speciosissimus

US: cortinarius
rainierensis
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Treatment
 Supportive
 Dialysis
 Kidney
Transplant
 Permanent kidney failure 8-50%
 No
role for prophylactic dialysis
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Newcomers to the Tox
Scene
 Amanita
-
smithiana
allenic norleucine; renal failure
 Tricholoma equestre
 -unknown toxin; severe
rhabdomyolysis
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Amanita smithiana
 All
13 cases in Pacific NW
 Onset 30 min - 12 hrs (early GI toxicity)
 Nausea, vomiting, anorexia, malaise,
dizziness, diaphoresis
 Acute renal failure 4-6 days later
 Elevated BUN, Creatinine, ALT
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
No deaths
 Prolonged dialysis
 Toxin: allenic norleucine (amino acid)
 Early onset GI symptoms vs. late (A. smithiana vs. C.
rainierensis)

Treatment:
- Supportive
- Activated charcoal
- Dialysis
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Tricholoma equestre
 12
patients-all had eaten 3 meals of
mushrooms
 Southwestern France
 Onset 24-36 hours
 Fatigue, myalgias, proximal muscle weakness
 Mean CPK 22,000 women; 34,000 men
 AST 1200/ALT 600
 3 deaths
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Tricholoma equestre
Toxin unknown-acute myopathy on biopsy
CK elevation reproduced in mice
No US cases
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References
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Auerbach, P. & Schneider, S. “Mushroom Toxicity” Wilderness Medicine 4th
Ed. Mosby 2001; 1141-1160
Bedry, R. et al “Wild mushroom intoxication as a cause of rhabdomyolysis”
NEJM 345; Sept 13, 2001; 798-802
Bickel, M. et al “Severe rhabdomyolysis, acute renal failure, and posterior
encephalopathy after ‘magic mushroom’ abuse” Euro J Em Med 2005; 12;
306-308
Burton, J. et al “Liver Transplantation in Mushroom Poisoning” J Clin
Gastroenterology 2002; 35(3); 276-280
Diaz, J. “Evolving global epidemiology, syndromic classification, general
management, and prevention of unknown mushroom poisoning” Crit Care
Med 2005 Vol. 33, No. 2; 419-426
Goldfrank, L.R: Mushrooms in Goldfrank’s Toxicologic Emergencies 8th Ed.
Goldfrank, L., Flomenbaum, N. et al. Appleton and Lange. 2006 1564-1576
Marx, J., Hochberger, R., Walls, R. Rosen’s Emergency Medicine 5th Ed Ch.
158 “Plants, Mushrooms, and Herbal Medicines” Mosby 2002; 2203-2205
Vicellio, P. & Shih, R. “Mushroom Poisoning” Emergency Toxicology 2nd
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Ed. Lippincott-Raven 1998; 1081-1086