II. Pathophysiology: Amatoxin - Amanitins (alpha, beta)
- Amanitins are Amatoxins (subset of Mycotoxins) found in various mushroom species
- Amanita (A. bisporigera, A. phalloides)
- Galerina (G. marginata)
- Lepiota (L. brunneoincarnata)
- Amanitins are cyclic octapeptides contained in carpophores (narrow stalks leading to fungal fruiting bodies)
- Potent RNA Polymerase inhibitors (blocks mRNA and Protein synthesis)
- Amanitin 0.1 mg/kg is a potentially lethal dose
- Some mushrooms may contain 0.2-0.4 mg a-Amanitin per dry weight mushroom (25-50 g per mushroom)
III. Pharmacokinetics: Amatoxin
- Rapid gastrointestinal absorption
- Hepatic uptake with bile salts and organic anions (via transport Proteins OATP1B3, NTCP)
- Excretion
- Renal excretion in the urine
- Bile excretion (but significant enterohepatic recirculation)
IV. Causes
- Amatoxins (esp. alpha-Amanitin)
- Death Cap (Amanita Phalloides)
- Destroying Angels (Amanita Bisporigera, Amanita ocreata, Amanita virosa)
- Isoxazole (muscimol and ibotenic acid)
- Amanita muscaria (Fly Agaric)
- Hallucinogenic mushrooms without renal and hepatic toxicity (not covered on this page)
V. Findings: Amatoxin
- Onset of intial symptoms (gastrointestinal) delayed 5-24 hours after ingestion
- Gastrointestinal
-
Liver
- Increased AST and ALT
- Coagulopathy
- Hyperbilirubinemia
- Hepatic necrosis
- Renal
- Neurologic
- Hepatic Encephalopathy
- Altered Level of Consciousness to coma
- Seizures
- Peripheral Neuropathy (sensory and motor)
- Endocrine
- Hypoglycemia
- Thyroid Hormone levels (T4 and T3) decreased
- Serum Calcium Decreased and Parathyroid Hormone and Calcitonin levels increased
- Insulin and C-Peptide levels increased
VI. Labs: Suspected Amatoxin Poisoning
- See Unknown Ingestion
- Complete Blood Count (CBC)
- Comprehensive metabolic panel (including renal and Liver Function Tests, Electrolytes, Glucose, Calcium)
- Serum Lactic Acid
- Coagulation studies (INR and PTT)
- Thyroid Stimulating Hormone (TSH)
- Free Thyroxine Level (Free T4)
- Alpha-Amanitin serum or urine levels (limited availability)
VII. Management: Amatoxin Poisoning
- Gastric Decontamination (Activated Charcoal)
- Supportive care
- Antiemetics
- Intravenous Fluids with dextrose
- Replace Electrolytes
- Admission for serial lab testing in suspected ingestions
- Enhanced elimination (extracorporeal removal)
- Strongly consider in early presentation in first 12 to 24 hours
- Hemodialysis or Hemoperfusion
- Hepatic uptake inhibitors of Amanitin
- Penicillin G infusion (500,000 IU/kg/day)
- Methylprednisolone
- Silibinin (Silybin)
- Active ingredient in Silymarin, extracted from seeds of Milk Thistle (Silybum marianum)
- Strongly consider in early presentations
- Other agents to consider
- Polymyxin B (starting at 2.5 mg/kg IV)
- Displaces alpha-Amanitin from RNA Polymerase II
- N-Acetylcysteine (NAC)
- Hepatoprotection
- Polymyxin B (starting at 2.5 mg/kg IV)
-
Acute Liver Failure
- ICU admission
- Transfer to tertiary center if transplant candidate
VIII. Prognosis: Factors Associated with Poor Outcomes in Amatoxin Poisoning
- Hypotension
- Mucosal Hemorrhage
- Uremia
- Thrombocytopenia
IX. Resources
- Amatoxin Mushroom Toxicity
X. References
- Carroll and Yakey (2026) Crit Dec Emerg Med 40(9): 36