22.Nov.2017-Expires: 7 days - Do not archive

Amanita phalloides

Amanita phalloides
22.Nov.2017-Expires: 7 days - Do not archive

IDENTIFICATION

The correct identification of the mushroom is imperative. If the identity is uncertain, or the patient’s signs and symptoms differ from those listed or are delayed in onset, seek clarification from a reliable source such as a mycologist or your local Poisons Information Center.
 
Further information on unidentified mushrooms can also be found by following the below link:
 
 

FAMILY NAME

Amanitaceae
 

GENUS NAME

Amanita
 

SPECIES NAME

Amanita phalloides
 

COMMON NAME(S)

Amanite phalloideDeadly amanita
Death capDeath cap mushroom
Deathcap amanitaDeathcap mushroom
Green death capOronge Verte
Stinking amanita
 
 

IMAGE

 
To search for more images, please click on the following link that will take you to Google Images. The content of this site is not controlled by TOXINZ and care should be used when assessing this information.
 
 

HABITAT

Amanita phalloides occurs mainly in deciduous and mixed deciduous forests, especially under oak trees but also near hornbeam or beech. The fungus avoids colder localities.[1]
 

USES

This mushroom is poisonous, however it may be mistaken for other edible mushrooms.

INTERVENTION CRITERIA

Intervention Level

Child and Adult

Decontamination, if appropriate, and medical observation is recommended for:
- Any ingestion of a cyclopeptide mushroom
- Exposures with intent to self-harm
 
History of dose ingested is not a reliable guide to management.
 

Observation Period

Observation at Home

All patients require medical attention.
 

Medical Observation

Any patient known to have ingested this type of mushroom must be admitted for monitoring and treatment, certainly those with symptoms or deranged biochemistry.
 

Investigations

If it is suspected that the patient has ingested cyclopeptide mushrooms, every effort should be made to get the mushroom identified by a mycologist.

When possible, a sample of the mushroom should be collected for identification. A whole mushroom, including the stalk and its base is preferable. The sample should be placed in a paper (not plastic) bag and then put in a sturdy container to protect the mushroom from damage. If the mushroom needs to be stored, it should be placed in the refrigerator, not the freezer.
 

Diagnostic Tests

Wieland (Meixner) Test:[2]
 
Determines presence of amatoxin
Methods
- Perform indoors away from sunlight and excessive heat
- Squeeze a small drop of fungus juice onto a piece of pulp paper
i.e. newspaper, phone book page
- Encircle wet stop with pencil to mark location
- Dry the spot with warm air
- Add a drop of concentrated hydrochloric acid to the dry spot
The presence of amatoxins is indicated by the formation of a blue color
 
False positives
- Use a control without amatoxins so false positives can be identified
- A false positive reaction can occur at high temperatures or exposure to sunlight
- Psilocybin, bufotenine, and certain terpines can give false positives[3][4]
 
This test is limited but can be helpful in the rapid testing in cases of suspected cyclopeptide poisoning.
 

Admission Criteria

Any patient who has ingested cyclopeptide mushrooms must be admitted.
 
Furthermore, any patient who has ingested an unknown mushroom but has features or biochemical changes indicative of cyclopeptide poisoning must be admitted.
 
The admission hospital will require the following resources:
Specific antidotes
Advanced care/ICU
Enhanced elimination
 

TREATMENT

TREATMENT SUMMARY

Any patient suspected of ingesting cyclopeptide-containing mushrooms should be admitted to hospital. Initial management consists of vigorous monitoring and replacement of expected fluid losses, which may be several liters per day.[5] Along with fluid replacement correction of metabolic disturbances such as acidosis, hypoglycemia, and electrolyte imbalances should be undertaken. The patient should be hemodynamically monitored and biochemical parameters followed closely.
 
Due to the low oral bioavailability of cyclopeptide mushrooms and the difficulty humans have in digesting large amounts of mushrooms, single dose activated charcoal may be given up to 12 hours following ingestion.[6][7] The use of multiple dose activated charcoal in the enhanced elimination of amatoxins is indicated up to 48 hours post-ingestion due to the extensive enterohepatic circulation of these toxins.[8] It is important that a good renal output is established during the first 48 hours following ingestion.
 
Supportive care is the mainstay of management. Although there is no clinically proven antidote for cyclopeptide mushroom poisoning, common therapies used have included silibinin, N-Acetylcysteine, benzylpenicillin, thioctic acid, and steroids. None of the antidotes used have undergone randomized, prospective clinical trials. Silibinin and N-Acetylcysteine appear to be the treatments of choice and should be considered in the management of these poisonings.[9][10][11][12] Efficacy has not been shown for the other therapies.[10] Benzylpenicillin, thioctic acid, and steroids are no longer recommended.[10]
 
Use of sedating drugs is not recommended due to their impact on the assessment of mental function/encephalopathy. Acute hepatic failure is a well-recognized concern and transplantation may be required.[13][14]
 
Advice should be sought from a specialist liver transplant unit
if:
The International Normalized Ratio (INR) is greater or equal to 2 at 24 hours or, 3 at any time
or
Creatinine is greater or equal to 200 umol/L (2.2 mg/dL)
or
pH is less than or equal to 7.3 or bicarbonate less than or equal to 18 mmol/L (18 mEq/L)
or
Blood pressure is low after volume loading (mean arterial pressure less than or equal to 60 mmHg)
or
The patient becomes encephalopathic
 
Early discussion of patients with a liver transplant unit is essential. Advice may be given and a decision to transport dependent upon results. In general it is considered desirable to transport patients prior to development of grade 2 encephalopathy.
 
Emergency Stabilization
Decontamination
Ingestion
Antidote(s)
Enhanced Elimination
Supportive Care
Gastrointestinal
Cardiovascular
Hepatic
Renal
Metabolic
Fluid and electrolytes
Hematologic
Neurologic
 

EMERGENCY STABILIZATION

Ensure Adequate Cardiopulmonary Function

Correct Hypovolemia

Immediately establish secure intravenous access.
 
Profound hypotension may occur requiring volume replacement.

CHILD
Where the systolic blood pressure is below normal blood pressure ranges for the age group:[15]
 
Age (years)
Normal Systolic Blood Pressure (mm Hg)
< 1
70 to 90
1 to 2
80 to 95
2 to 5
80 to 100
5 to 12
90 to 110
> 12
100 to 120
 
Administer normal (0.9%) saline
10 mL/kg IV over 5 to 10 minutes
 
If the systolic blood pressure does not return to the normal range, give a further 10 mL/kg body weight normal saline over 5 to 10 minutes. If intravenous access cannot be obtained consider intra-osseus access.
 
ADULT
Administer a bolus of normal saline if systolic blood pressure is less than 100 mmHg.
 
Normal (0.9%) saline dose:
10 mL/kg IV over 5 to 10 minutes
 
If the systolic blood pressure does not return to the normal range, give a further 10 mL/kg body weight normal saline over 5 to 10 minutes.
 
If hypotension can not be reversed then follow standard protocols for the management of hypotension.

Emergency Monitoring

Seizure activity
Blood pressure
Heart rate
ECG
Fluid balance
Serum electrolytes
Renal function
Liver function
 

DECONTAMINATION

Ingestion

Single Dose Activated Charcoal

Administer activated charcoal up to 12 hours following a potentially toxic ingestion.
 
Single dose activated charcoal[16]
CHILD
1 to 2 g/kg orally
ADULT
50 to 100 g orally
 

ANTIDOTE(S)

Silibinin

Animal studies have shown that silibinin (Milk thistle) prevents the uptake of amatoxins by hepatocytes, reducing enterohepatic circulation and therefore enhancing renal elimination. Furthermore, silibinin stimulates DNA-dependent RNA polymerases, leading to an increase in RNA synthesis.[17] However, controlled human studies are still pending. Unfortunately, silibinin is not widely available.
 

Indications

Silibinin is indicated in:[18]
All patients presenting with cyclopeptide mushroom ingestion
 

Dose and Administration

Silibinin dose:[19][20]
 
CHILD
IV
Initial dose 5 mg/kg IV over 1 hour
Maintenance dose of 20 mg/kg as a continuous infusion
 
ADULT
IV
Initial dose 5 mg/kg IV over 1 hour
Maintenance dose of 20 mg/kg as a continuous infusion
 
Treatment should be continued for up to 72 hours, or until significant declines in INR and liver function tests are apparent.
 

Precautions

Documented hypersensitivity to silibinin.

Pregnancy
Recommended doses could be administered during pregnancy without being harmful to the fetus.[21]
 

Adverse Effects

Silibinin appears to be well tolerated. However the following adverse effects have been reported following administration:[22][10]
Gastrointestinal upset (nausea, vomiting, diarrhea, abdominal pain)
Intermittent episodes of sweating
Arthralgia
Pruritus
Headache
Urticaria
Weakness
 

Acetylcysteine

Animal studies indicate that sublethal doses of amatoxins deplete hepatic glutathione content.[23] N-acetylcysteine is thought to serve as a glutathione precursor and consequently, the administration of N-acetylcysteine in cyclopeptide mushroom poisoning may prevent reduced glutathione levels and subsequent hepatocellular damage.[11][24] Additionally N-acetylcysteine has been shown to reduce morbidity and mortally in severe hepatic failure irrespective of origin.[25] It is therefore recommended in cyclopeptide mushroom poisoning.
 

Indications

N-acetylcysteine should be administered in:[21]
All patients presenting with cyclopeptide mushroom ingestion
 

Dose and Administration

While acetylcysteine is recommended to be administered intravenously in 5% dextrose in water, 1/2 normal (0.45%) saline may be substituted if necessary.[26] It is recommended that acetylcysteine dose for adults be calculated for actual body weight rounded up to the nearest 10 kg with a ceiling weight of 110 kg.[27]
 
CHILD
 
Children 20 kg or less body weight:[27]
150 mg/kg in 3 mL/kg of 5% dextrose over 60 minutes
Followed by 50 mg/kg in 7 mL/kg of 5% dextrose over 4 hours
Followed by 100 mg/kg in 14 mL/kg of 5% dextrose over 16 hours
 
Children > 20 kg body weight:[27]
150 mg/kg in 100 mL of 5% dextrose over 60 minutes
Followed by 50 mg/kg in 250 mL of 5% dextrose over 4 hours
Followed by 100 mg/kg in 500 mL of 5% dextrose over 16 hours
 
Closely monitor fluid and electrolyte balance.
 
ADULT
 
Administer:[27]
150 mg/kg in 200 mL diluent IV over 60 minutes
Followed by 50 mg/kg in 500 mL diluent IV over 4 hours
Followed by 100 mg/kg in 1,000 mL diluent over 16 hours
 
 

Precautions

Pregnancy
Acetylcysteine should be administered to pregnant patients following the standard adult regimen. Transplacental transport of acetylcysteine is not thought to be clinically significant,[28] however, delay in initiation of acetylcysteine treatment is associated with increased incidence of spontaneous abortion and fetal death.[29] Acetylcysteine is not considered teratogenic.[30]
 

Adverse Effects

Anaphylactoid Reaction
Six to 23% of patients receiving IV acetylcysteine develop an anaphylactoid reaction.[31][32] These do not represent an immunological (allergic) reaction; rather, they are thought due to a direct dose-dependent effect on histamine release and generally occur within the first two hours of an infusion.
 
History of previous anaphylactoid reaction to acetylcysteine does not contraindicate use. If there is concern of recurrence of the reaction the patient may be pre-treated 15 minutes before commencement of the infusion with an antihistamine.[33]
 
Effects range from mild flushing to urticaria, angioedema, or bronchospasm. Hypotension may occasionally occur. Asthmatics appear more at risk. However, effects are usually easily managed and there is no reason to withhold acetylcysteine from any patient when indicated.[33]
 
Hyponatremia
Hyponatremia has been reported in children if administered acetylcysteine in 5% dextrose following adult protocols for dilution of infused dose.[34]
 

ENHANCED ELIMINATION

Maintain Good Renal Output 

Significant amounts of amatoxins are eliminated in the urine,[17] especially during the 48 hours following ingestion.[6] Therefore, maintenance of a good urine output (~200 mL/h) should be ensued, particularly during the first 48 hours.[9] Forced diuresis with a loop diuretic does not increase amatoxin excretion and should be avoided.[10]
 

Multiple Dose Activated Charcoal

Multiple dose activated charcoal should be administered within 48 hours of ingestion to remove any unabsorbed material and to interrupt the enterohepatic circulation of amatoxins.[6][8][12][35] Amatoxins are easily absorbed though the intestinal tract and rapid hepatic uptake occurs via the bile salt transport system. Approximately 60% if the absorbed dose is excreted into the bile, returning to the liver via enterohepatic circulation.[36]
 
Multiple dose activated charcoal dose
CHILD
0.25 g/kg bolus/hourly
ADULT
12.5 g bolus/hourly
 
Administer orally or via nasogastric tube and continue until signs of clinical and biochemical improvement.[37]
 

Other Forms of Enhanced Elimination

Other forms of enhanced elimination including plasmapheresis,[38] peritoneal dialysis,[39] hemodialysis,[40] and hemoperfusion[41][42] have occasionally yielded success but the results are inconsistent.[43] No prospective clinical trial comparing groups of patient treated with and without elimination techniques has been reported and overall these methods are generally no longer recommended.[9] However, hemoperfusion may be of some benefit for patients with pre existing renal disease or if initiated early (within 24 hours) following poisoning.[9][44][41] Hemodialysis should be instituted if renal failure occurs.
 

SUPPORTIVE CARE

Monitoring

Cardiac function including:
Blood pressure
Heart rate
12 lead ECG
Renal function including:
Serum urea
Serum creatinine
Renal output
Serum electrolytes including:
Sodium
Potassium
Calcium
Liver function tests including:
ALT
AST
INR
Serum bilirubin
Urinary urobilinogen
Full blood count including:
Prothrombin time
Fibrinogen
Intracranial pressure
Arterial blood gas
Blood glucose
 

Gastrointestinal

Gastrointestinal Irritation

The amatoxins of cyclopeptide mushrooms target cells with high mitotic indices such as the gastrointestinal mucosa. Symptoms include abdominal pain, nausea, vomiting, and cholera-like diarrhea.[45] Patients will require robust supportive care including IV fluids, electrolyte replacement, and antiemetics.[35][18] In the absence of fluid replacement vomiting and diarrhea may induce rapid dehydration, hemoconcentration, and hypovolemic shock.[46]
 
Observe patient for:
Nausea
Vomiting
Abdominal pain
Hematemesis
Diarrhea
 
Monitor:
Blood pressure
Fluid balance
Serum electrolytes (if severe)
Acid-base (if severe)
 
Manage gastrointestinal irritation following standard treatment protocols.
 

Cardiovascular

Hypovolemia

Hypovolemia may occur due to the large fluid and electrolyte losses that occur as a result of significant vomiting and diarrhea exhibited in the initial gastrointestinal stage of cyclopeptide poisoning. Correction of fluid and electrolyte abnormalities is mandatory.[47]
 
Monitor:
Blood pressure
Renal output
Renal function
 
Manage hypovolemia following standard treatment protocols.

Hepatic

Acute Hepatic Failure

Cyclopeptide mushrooms contain amatoxins, liver toxins that cause liver necrosis with acute hepatic failure and subsequent complications, including hepatic coma, coagulation disorders, and renal failure.[9] Clinical signs of hepatocellular damage usually develop on the third to fourth day after ingestion. Clinical presentation may only include a mild jaundice and hepatomegaly.[45] Elevated liver enzyme levels and elevated bilirubin are common.[18] In severe cases, hepatitis follows a fulminant course with marked jaundice and hepatic coma accompanied by renal failure and cardiovascular collapse.[48]
 
Liver transplants have become a well established option in the treatment of liver failure due to amatoxins.[49] Advice should be sought from a liver transplant unit if the International Normalized Ratio (INR) is greater or equal to 2 at 24 hours or 3 at any time; or, if the patient becomes encephalopathic.
 
Monitor:
Hepatic enzymes
International normalized ratio (INR)
Serum bilirubin
Plasma glucose
Arterial pH
Serum electrolytes
Serum creatinine
Serum urea
 
Manage acute hepatic failure following standard protocols.
 

Renal

Acute Renal Failure

Two kinds of renal failure may be observed following cyclopeptide mushroom ingestion. During the gastrointestinal phase of poisoning, a functional renal failure is frequent.[50] It is associated with hypovolemia and is secondary to fluid losses and hypoperfusion of the kidneys. Rapid and aggressive treatment of dehydration and hypovolemia should reverse this form of renal failure.
 
The second kind of renal failure may arise during the hepatorenal phase of poisoning, either occurring secondary to severe hepatitis[51] or to direct toxic renal damage.[9] Renal failure occurring in this phase usually resolves as hepatic function improves but may require hemodialysis as a supportive measure.
 
Patients should be monitored for the onset of renal failure:
Urine output
Serum creatinine
Blood urea nitrogen (urea)
Proteinuria
Hematuria
Loin pain may occur
 
Manage following standard treatment protocols for acute renal failure.
 

Metabolic

Metabolic Acidosis

During the initial gastrointestinal phase of cyclopeptide mushroom poisoning, metabolic acidosis may occur due to fluid and electrolyte imbalances, particularly large losses of sodium bicarbonate. In contrast, metabolic acidosis in the late stages of cyclopeptide mushroom poisoning is typically a consequence of hepatic failure and should be treated as such.[50]
 
Monitor:
Arterial blood gases (pH, bicarbonate, pCO2, pO2)
Plasma lactate
Base excess
 
Follow standard protocols for the management of metabolic acidosis.
 

Hypoglycemia

In severe hepatic failure, glucose metabolism is often disturbed resulting in hypoglycemia.[52] Patients with evidence of hepatic dysfunction should be monitored for hypoglycemia.
 
Monitor serum glucose.
 
Follow standard protocols for the management of hypoglycemia.

Fluid and Electrolytes

Electrolyte Abnormalities

The gastrointestinal phase of cyclopeptide mushroom poisoning often results in dehydration with electrolyte imbalance, including hypokalemia, hyponatremia, and hypochloremia.[50] Electrolyte replacement, either oral or parenteral, should be guided by symptomatology, ECG findings, and repeat serum levels.
 
Monitor serum electrolytes.
 
Manage serum electrolyte abnormalities following standard protocols.
 

Hematologic

Coagulopathy

Coagulopathy occurs as a consequence of acute hepatic failure with cyclopeptide toxicity. Coagulopathy should be managed in conjunction with hepatic failure. Fresh frozen plasma (FFP) or coagulation factor replenishment may be required.
 
Monitor:
International normalized ratio (INR)
Activated partial thromboplastin time (aPTT)
 
Manage coagulopathy following standard treatment recommendations.

Neurologic

Seizures

Neurological symptoms occur secondary to acute hepatic failure and may include seizures, encephalopathy, somnolence, confusion, and coma.[53] Seizures should respond to treatment with benzodiazepines. If benzodiazepines fail to control the seizures, then barbiturates can be administered.
 
Observe the patient closely for onset of seizure activity.
 

DISCHARGE CRITERIA

Discharge after development of hepatic or renal failure, or other consequences, should follow standard protocols for those conditions.
 

FOLLOW UP

Standard protocols should be used for follow-up of patients suffering hepatic or renal failure, including advice that patients should abstain from alcohol for six weeks to allow regeneration of the liver.
 

PROGNOSIS

In the early part of the 20th century mortality was up to 70%.[54] Since the 1970's with more advanced medical supportive care and the introduction of more specific treatment protocols, overall mortality diminished to below 25%.[55][56][57] Furthermore, recent retrospective analysis's have shown overall mortalities as low as 4.8%[58] and 1.8%.[59]
 
The prognosis is poorer with large doses, a short latency period between ingestion and onset of symptoms, severe coagulopathy, an age below 10 years, or in patients who present to hospital more than 36 hours post ingestion.[55][59][60][61] A fatal outcome is predicted if the prothrombin index is less than 25% combined with serum creatinine greater than 106 mmol/L from day 3 to 10.[49]
 

SIGNS AND SYMPTOMS

Cyclopeptide mushroom ingestion produces the Phalloides syndrome, which typically exhibits a quadriphasic course, and appears to be dose related.
 
Phase 1 and 3 are latent periods where the patient generally feels relatively well. Phase 2 begins approximately 12 hours after mushroom ingestion and consists predominantly of severe gastrointestinal symptoms, which leads to significant water and electrolyte loss. The final phase is hepatorenal, where severe hepatotoxicity may occur and hepatic and renal failure can ensue. In fatal cases, death may occur six to 16 days following ingestion.[62]
 

Routes of Exposure

Cyclopeptide mushrooms are usually ingested in fresh condition. Poisoning typically occurs as a result of amateur mushroom gatherers mistaking the mushrooms for various edible varieties. The toxins remain stable when boiled, thus poisoning is possible whether the mushrooms are eaten raw or cooked.[63]
 

Onset/Duration of Symptoms

Symptoms following the ingestion of amatoxin-containing mushrooms occur in four phases.
 
NOTE: Time frames may vary considerably to those listed below.
 
Latent asymptomatic phase (< 24 hours and usually up to 12 hours post-ingestion)
No symptoms
Gastrointestinal phase (6 to 24 hours post-ingestion)
Abdominal pain
Vomiting
Severe diarrhea
Hypovolemia
Electrolyte disturbances
Acid-base disturbance
Period of well-being (24 to 48 hours post-ingestion)
Hepatic and renal function deteriorates
Hepatic phase (3 to 5 days post-ingestion)
LFT increases
Acute hepatic failure
Acute renal failure
 
In fatal cases, death may occur 6 to 16 days following ingestion due to hepatic and/or renal failure.[62]
 

Severity of Poisoning

Mild Cyclopeptide ToxicityModerate Cyclopeptide ToxicitySevere Cyclopeptide Toxicity
Nausea
Vomiting
Diarrhea
Abdominal pain
Electorlyte imbalances
Hypoglycemia
Right upper quadrant tenderness
Hepatitis
Renal dysfunction
Metabolic acidosis
Coagulopathy
Fulminant hepatic failure
Acute renal failure
Hepatic encephalopathy
Death
 

ACUTE EFFECTS (ORGAN SYSTEM)

Gastrointestinal

Nausea[44]
Vomiting[44][64]
Diarrhea[64] (may be severe)[44]
Abdominal pain[65][35][44][47]
 

Hepatic

Jaundice[66]
Hepatomegaly[45]
Elevated liver enzymes[12][67]
Increased International Normalized Ratio (INR)[12][59]
Coagulopathy[48]
Hepatic encephalopathy[66]
Hepatic coma (in severe cases)[47][55][66][68]
 

Renal

Oliguria[68]
Anuria[67]
Hematuria[47]
Acute tubular necrosis[69]
Renal failure[70]
 

Neurologic

Neurological symptoms are believed to be secondary to hepatorenal failure.
 
Somnolence[66]
Confusion[67]
Encephalopathy[53]
Seizure[68]
Raised intracranial pressure[71]
Neuropathy[53]
Coma[66]
 

Cardiovascular

Tachycardia[69][72]
Hypotension[47]
Cardiomyopathy[73]
 

Fluid and Electrolytes

Dehydration[68]
Hypovolemia[9]
Hypokalemia[9]
Hyponatremia[74]
Hypochloremia
Hypocalcemia[50]
 

Hematologic

Hypofibrinogenemia[5]
Hypoprothrombinemia[75]
Coagulopathy[52]
Epistaxis[76]
Gastrointestinal hemorrhage[5]
Impaired synthesis of clotting factors[77]
 

Metabolic

Hypoglycemia[71][78]
Metabolic acidosis[78]
Lactic acidosis[9][10][12][44][50]
 

Respiratory

Hyperventilation
Hypoventilation
Apnea
Hemorrhagic pulmonary alveolitis[79]
Adult respiratory distress syndrome[80]
Respiratory arrest[68]
 

Hormonal

Hyperinsulinism[50]
Hyperparathyroidism[50]
Hypothyroidism[50]
Elevated serum calcitonin levels[50]
 

Dermatologic

Pallor[44]
Jaundice[70]
Icteric sclera
 

TOXICITY

The toxic content of fungi may vary from year to year due to various factors that affect growth, such as available moisture and spring temperatures. Thus, it is difficult to establish an association between the severity of symptoms and the ingestion of a specific amount of fungus material.

HUMAN

Acute

Effects are dose-dependent. The following list is an approximate guide of how to evaluate the dose taken:
 
The minimal lethal dose of amatoxins in adults is:
<0.1 mg/kg[81]
 
Concentrations of 5 to 15 mg amatoxins per gram of dried mushroom have been found.[81][82] This means that the following amounts of mushroom could kill a healthy adult:[54][82]
Amanita
1 cap
Galerina
15 to 20 caps
Lepiota
30 caps
 
Prognosis appears to be primarily determined by the quantity of mushroom eaten (dose of toxins per kg body weight). Therefore, mortality is far higher in children under 10 years of age than in adults.[55]
 

ANIMAL

Acute

AMATOXIN
 
LD50 IP, Rat
4 mg/kg[83]
Death occurs in 2 to 5 days
LD50 IP, Mouse
0.3 mg/kg[83]
 
LD50 IV, Dog
0.1 mg/kg[83]
 
PHALLOTOXIN
 
LD50 IP, Mouse
2.5 mg/kg[83]
 

REPRODUCTION

PREGNANCY

Amatoxins do not cross the placenta following maternal exposure to cyclopeptide mushrooms.[84] Fetal abnormality has not been reported following ingestion during the second or third trimester. While abortion is not recommended, fetal risk cannot be excluded and monitoring of the fetus should be intensified.
 
There have been a number of cases of maternal intoxication not causing any significant effects to the fetus.[85][21][86][87][88]
 
A 22-year-old woman in the 11th week of pregnancy inadvertently ingested Amanita phalloides. Treatment consisted of intravenous hydration, and administration of silymarine and N-acetylcysteine. No fetal damage was observed and the birth and development of the infant proceeded without incident.[21] Another case reported a 26 year old woman in the 22nd week of pregnancy suffering Amanitia phalloides poisoning. The patient was treated successfully and went on to deliver a normal healthily baby.[86]
 
In contrast, in one reported case of poisoning in the first trimester, the mother developed toxic hepatitis. She was successfully managed, however, a therapeutic abortion was performed because of speculated fetal toxicity. The fetal liver was found to be consistent with cyclopeptide poisoning. Treatment carried out on the mother was not mentioned.[89]
 

LACTATION

It is unknown if the ingestion of these mushrooms results in excretion of amatoxins into breast milk. Breast-feeding patients who have ingested cyclopeptide mushrooms should be advised to avoid breast feeding.
 

FERTILITY

It is unknown if exposure to, or ingestion of, this fungus causes impaired fertility.
 

TOXIC COMPONENTS

Cyclopeptide mushrooms contain three classes of toxin; amatoxins, phallotoxins, and virotoxins. Amatoxins are responsible for the majority of effects seen following the ingestion of cyclopeptide mushrooms.[9]
 
Amatoxins
Phallotoxins
Virotoxins
 
Alpha amanitin
Beta amanitin
Gamma amanitin
Epsilon amanitin
Amanin
Amaninamide
Amanullin
Amanullinic acid
Proamanullin
 
Phalloidin
Phalloin
Prophalloin
Phallisin
Phallicin
Phallacidin
Phallisacin
 
Viroidin
Alloviroidin
Desoxoviroidin
[Ala]viroidin
[Ala]deoxoviroidin
Viroisin
Desoxoviroisin[90]
 
Amatoxins are very stable, mushrooms remain toxic even after long periods of storage. They are also thermostable and not removed by cooking or freezing.[78][63]
 

Plant Content

All parts of cyclopeptide mushrooms are poisonous. Amatoxin concentrations vary greatly within and between cyclopeptide mushroom species.
 
The following concentrations of amatoxins expressed in mg/g of dry tissue have been reported:
 
Amanita phalloides
2 to 7.3
Amanita verna
0.4 to 4.6
Amanita virosa
1.2 to 2.6
Amanita bisporigera
2.4
Galerina autumnalis
0.8 to 1.5
Galerina marginata
0.4
 

TOXIC MECHANISM

Cyclopeptide-containing mushrooms are responsible for producing the phalloides syndrome, a syndrome that is responsible for approximately 90% of all lethal mushroom poisonings.[91] Cyclopeptide mushrooms contain three classes of toxin; amatoxins, phallotoxins, and virotoxins. Amatoxins are responsible for the majority of toxic effects seen following the ingestion of these mushrooms.[9]
 
Amatoxins are bicyclic octapeptides with an indole-(R)-sulphoxide bridge that inhibit RNA polymerase II, thus affecting mRNA synthesis.[35][67] This interferes in the transcription of DNA and leads to cellular necrosis in cells with high rates of protein synthesis, and where initial exposure to high doses of the toxins occurs (i.e., the intestinal mucosa, the hepatocytes of the liver, and the proximal tubules of the kidney).[9][92] The most significant injury is hepatic necrosis. This mechanism is thought to account for the delayed onset of severe gastroenteritis and the long latency period of the hepatic phase of intoxication.[17]
 
Phallotoxins are bicyclic hepatapeptides with an indole/thio-ether bridge.[93] It is probable that the phallotoxins play no role in human poisoning, as they are not absorbed from the gastrointestinal tract.[10][94] When administered parenterally to laboratory animals, phallotoxins destroy the endoplasmic reticulum and mitochondria of the liver cells and induce necrosis of hepatocytes. Phalloidin increases the permeability of the plasma membrane of hepatocytes by binding to the actin G of plasma membranes and polymerizing actin G irreversibly.[95] Phallatoxins are approximately one-tenth as toxic as the amatoxins.
 
Finally, viratoxins are monocyclic hepatapeptides, which are thought to be comparable in their biological activity to that of the phallotoxins in regard to their affinity for F-actin and their toxic action in mice.[96] Virotoxins are not thought to exert any toxicity after ingestion in humans.[9]
 

BIOLOGICAL LEVELS - TOXIC

Serum levels of amatoxins are not readily available,[9][67] do not correlate with severity of poisoning,[10] and are not necessary for clinical management.
 

SI Unit Conversion

To convert an alfa-amanitin concentration expressed in mg/L into mmol/L:
Multiply the mg/L by 0.0011
 
To convert an alfa-amanitin concentration expressed in mmol/L into mg/L:
Multiply the mmol/L by 918.97
 
To convert an beta-amanitin concentration expressed in mg/L into mmol/L:
Multiply the mg/L by 0.0011
 
To convert an beta-amanitin concentration expressed in mmol/L into mg/L:
Multiply the mmol/L by 919.95
 
To convert an phalloidin concentration expressed in mg/L into mmol/L:
Multiply the mg/L by 0.0013
 
To convert an phalloidin concentration expressed in mmol/L into mg/L:
Multiply the mmol/L by 788.87
 

Toxic Serum Level

Concentrations of amatoxins can be detected in some patients up to 30 hours post ingestion.
 
Amatoxin toxic plasma concentrations
 
In a group of 29 patients serum amatoxins were detectable in 65% of patients. Concentrations were:
0.5 to 2.4 ug/L[6]
 
In patients with Amanita phalloides intoxication serum alfa amantin concentrations were:
70 to 90 ug/L[97]
 
Another study of 45 patients with Amanita phalloides poisoning, demonstrated plasma alfa amatoxin concentrations of:
8 to 190 ug/L[98]
 

Toxic Urine Levels

Urine amatoxin detection could potentially be suitable for the early diagnosis of poisoning.[99] However, there is no information on the relationship between urine levels and severity of poisoning.[9]
 
Amatoxin toxic urine concentrations
 
In a group of 29 patients urinary amatoxins were detectable. Concentrations were:
0.5 to 56 ug/L[6]
 
Urinary amatoxins were detectable in 15 out of 24 patients in another study. Concentrations were:
< 4800 ug/L[98]
 

KINETICS

ABSORPTION

Oral Absorption
Amatoxins: Rapidly absorbed from the GI tract following oral administration[9]
Phallotoxins: Not absorbed from the GI tract following oral administration[98]
Onset of Action
Amatoxins: Delayed 6 to 24 hours[100]
 

DISTRIBUTION

Distribution
  1. High concentrations are found in the gastroduodenal fluid up to 100 hours after ingestion[98]
Volume of Distribution
  1. Unknown in humans
  2. 160 to 290 mL/kg in dogs[101]
Plasma Protein Binding
  1. Amatoxins are not bound to albumin[101][102]
Lipid Solubility
Does not cross the placenta
  1. Amatoxins do not cross the placenta[84]
 

METABOLISM

Metabolism
  1. In experimental studies, no metabolites could be detected after administration of radioactive amanitin[101]
 

ELIMINATION

Excretion
Amatoxins are excreted in large quantities in the urine in the first days following ingestion.[98]
  1. In dogs 83 to 88% was recovered in the urine
  2. Amatoxins may be detected in urine as early as 90 to 120 minutes post ingestion, however can be detected in urine up to 96 hours post ingestion
  3. In dogs <10% recovered in bile
  4. Amatoxins excreted in bile may be reabsorbed via enterohepatic recirculation[101]
Half-life
Therapeutic
  1. Eliminated very quickly from serum
  2. In a group of patients, amatoxins disappeared rapidly in serum
  3. In two patients only, amatoxins could still be detected in serum after the 36 hours post ingestion[98]
 

DESCRIPTION

PLANT ATTRIBUTES

Amanita phallodies has a large round cap 5 to 15 cm in diameter. The cap is light greenish-olive to greenish-yellow colored with white gills and spores. The stalk is white with grayish-olive scales, 8 to 15 cm long and 1 to 2 cm thick. Near the top of the stalk 1 to 1.5 cm below the cap, the remains of the partial veil are seen as a skirtlike, floppy annulus (ring). At the base of the stalk is a large white membranous volva.[1]
 

CAS NUMBER

Amantin:
11030-71-0
Alfa-amanitin:
23109-05-9
Beta-amanitin:
21150-22-1
Phalloidin:
17466-45-4
 

PHYSICOCHEMICAL PROPERTIES

AMATOXINS:
 
Colorless, crystalline substance
 
ALFA-AMANITIN:
 
Molecular Weight
918.98 918.98
 
BETA-AMANITIN:
 
Molecular Weight
919.97 919.97
Melting Point
254 to 255 degrees C254 to 255 degrees C
Solubility
Water: soluble
Ethanol: soluble
Methanol: soluble
Aqueous butanol: soluble
 
PHALLOTOXINS:
 
Colorless, crystalline substance
 
PHALLOIDIN:
 
Molecular Weight
788.88 788.88
Melting Point
280 to 282 degrees C280 to 282 degrees C
Solubility
Water (hot): slightly soluble
Ethanol: freely soluble
Methanol: freely soluble
Butanol: freely soluble
Pyridine: freely soluble[103][104]
 

REFERENCES

 
[1] Bresinsky A, Besl H. A colour atlas of poisonous fungi. London: Wolfe Publishing Ltd; 1990. p. 26-35.
[2] Benjamin DR. Mushrooms: poisons and panaceas: a handbook for naturalists, mycologists, and physicians. New York: WH Freeman and Company; 1995. p. 191-2.
[3] Beuhler M, Lee DC, Gerkin R. The Meixner test in the detection of alpha-amanitin and false-positive reactions caused by psilocin and 5-substituted tryptamines. Ann Emerg Med 2004 Aug; 44 (2): 114-20.
[4] Beutler JA, Vergeer PP. Amatoxins in American mushrooms: Evaluation of the Meixner test. Mycologia 1980; 72 (6): 1142-9.
[5] Pinson CW, Daya MR, Benner KG, Norton RL, Deveney KE, Ascher NL, Roberts JP, Lake JR, Kurkchubasche AG, Ragsdale JW. Liver transplantation for severe Amanita phalloides mushroom poisoning. Am J Surg 1990 May; 159 (5): 493-9.
[6] Vesconi S, Langer M, Iapichino G, Costantino D, Busi C, Fiume L. Therapy of cytotoxic mushroom intoxication. Crit Care Med 1985 May; 13 (5): 402-6.
[7] Bergoz R. Trehalose malabsorption causing intolerance to mushrooms. Report of a probable case. Gastroenterology 1971 May; 60 (5): 909-12.
[8] Busi C, Fiume L, Costantino D, Langer M, Vesconi F. Amanita toxins in gastroduodenal fluid of patients poisoned by the mushroom, Amanita phalloides. [Letter] N Engl J Med 1979 Apr 5; 300 (14): 800.
[9] Karlson-Stiber C, Persson H. Cytotoxic fungi--an overview. Toxicon 2003 Sep 15; 42 (4): 339-49.
[10] Enjalbert F, Rapior S, Nouguier-Soule J, Guillon S, Amouroux N, Cabot C. Treatment of amatoxin poisoning: 20-year retrospective analysis. J Toxicol Clin Toxicol 2002; 40 (6): 715-57.
[11] Montanini S, Sinardi D, Pratico C, Sinardi AU, Trimarchi G. Use of acetylcysteine as the life-saving antidote in Amanita phalloides (death cap) poisoning. Case report on 11 patients. Arzneimittelforschung 1999 Dec; 49 (12): 1044-7.
[12] 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.
[13] Panaro F, Andorno E, Morelli N, Casaccia M, Bottino G, Ravazzoni F, Centanaro M, Ornis S, Valente U. Liver transplantation represents the optimal treatment for fulminant hepatic failure from Amanita phalloides poisoning. [Letter] Transpl Int 2006 Apr; 19 (4): 344-5.
[14] Araz C, Karaaslan P, Esen A, Zeyneloglu P, Candan S, Torgay A, Haberal M. Successful treatment of a child with fulminant liver failure and coma due to Amanita phalloides poisoning using urgent liver transplantation. Transplant Proc 2006 Mar; 38 (2): 596-7.
[15] Mackway-Jones K, Molyneux E, Phillips B, Wieteska S, editors. Advanced paediatric life support: the practical approach. 3rd ed. London: BMJ Books; 2001.
[16] Fountain JS, Beasley DM. Activated charcoal supercedes ipecac as gastric decontaminant. N Z Med J 1998 Oct 23; 111 (1076): 402-4.
[17] Hruby K, Csomos G, Fuhrmann M, Thaler H. Chemotherapy of Amanita phalloides poisoning with intravenous silibinin. Hum Toxicol 1983 Apr; 2 (2): 183-95.
[18] Floersheim GL. Treatment of human amatoxin mushroom poisoning. Myths and advances in therapy. Med Toxicol 1987 Jan-Feb; 2 (1): 1-9.
[19] Murray L, Little M, Pascu O, Hoggett K. Toxicology handbook. 3rd ed. Sydney, Australia: Elsevier; 2015. p. 51.
[20] Hoffman RS, Howland MA, Lewin NA, Nelson LS, Goldfrank LR, editors. Goldfrank’s toxicologic emergencies. 10th ed. New York: McGraw-Hill; 2014. p. 1515-6.
[21] Boyer JC, Hernandez F, Estorc J, De La Coussaye JE, Bali JP. Management of maternal Amanita phalloides poisoning during the first trimester of pregnancy: a case report and review of the literature. Clin Chem 2001 May; 47 (5): 971-4.
[22] An adverse reaction to the herbal medication milk thistle (Silybum marianum). Adverse Drug Reactions Advisory Committee. Med J Aust 1999 Mar 1; 170 (5): 218-9.
[23] Kawaji A, Sone T, Natsuki R, Isobe M, Takabatake E, Yamaura Y. In vitro toxicity test of poisonous mushroom extracts with isolated rat hepatocytes. J Toxicol Sci 1990 Aug; 15 (3): 145-56.
[24] Chyka PA, Butler AY, Holliman BJ, Herman MI. Utility of acetylcysteine in treating poisonings and adverse drug reactions. Drug Saf 2000 Feb; 22 (2): 123-48.
[25] Harrison PM, Wendon JA, Gimson AE, Alexander GJ, Williams R. Improvement by acetylcysteine of hemodynamics and oxygen transport in fulminant hepatic failure. N Engl J Med 1991 Jun 27; 324 (26): 1852-7.
[26] Cumberland-Pharmaceuticals. Acetadote (Acetylcsyteine) Injection - Package Insert. Nashville TN: Cumberland Pharmaceuticals Inc, 2011: [Cited 27 Jan 2012]. URL: http://www.acetadote.net
[27] Chiew AL, Fountain JS, Graudins A, Isbister GK, Reith D, Buckley NA. Summary statement: new guidelines for the management of paracetamol poisoning in Australia and New Zealand. Med J Aust 2015 Sep 7; 203 (5): 215-8.
[28] Selden BS, Curry SC, Clark RF, Johnson BC, Meinhart R, Pizziconi VB. Transplacental transport of N-acetylcysteine in an ovine model. Ann Emerg Med 1991 Oct; 20 (10): 1069-72.
[29] Riggs BS, Bronstein AC, Kulig K, Archer PG, Rumack BH. Acute acetaminophen overdose during pregnancy. Obstet Gynecol 1989 Aug; 74 (2): 247-53.
[30] Janes J, Routledge PA. Recent developments in the management of paracetamol (acetaminophen) poisoning. Drug Saf 1992 May-Jun; 7 (3): 170-7.
[31] Mant TG, Tempowski JH, Volans GN, Talbot JC. Adverse reactions to acetylcysteine and effects of overdose. Br Med J (Clin Res Ed) 1984 Jul 28; 289 (6439): 217-9.
[32] Bailey B, McGuigan MA. Management of anaphylactoid reactions to intravenous N-acetylcysteine. Ann Emerg Med 1998 Jun; 31 (6): 710-5.
[33] Schmidt LE, Dalhoff K. Risk factors in the development of adverse reactions to N-acetylcysteine in patients with paracetamol poisoning. Br J Clin Pharmacol 2001 Jan; 51 (1): 87-91.
[34] Sung L, Simons JA, Dayneka NL. Dilution of intravenous N-acetylcysteine as a cause of hyponatremia. Pediatrics 1997 Sep; 100 (3 Pt 1): 389-91.
[35] O'Brien BL, Khuu. A fatal Sunday brunch: Amanita mushroom poisoning in a Gulf Coast family. Am J Gastroenterol 1996 Mar; 91 (3): 581-3.
[36] Kroncke KD, Fricker G, Meier PJ, Gerok W, Wieland T, Kurz G. alpha-Amanitin uptake into hepatocytes. Identification of hepatic membrane transport systems used by amatoxins. J Biol Chem 1986 Sep 25; 261 (27): 12562-7.
[37] Position statement and practice guidelines on the use of multi-dose activated charcoal in the treatment of acute poisoning. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. J Toxicol Clin Toxicol 1999; 37 (6): 731-51.
[38] Jander S, Bischoff J, Woodcock BG. Plasmapheresis in the treatment of Amanita phalloides poisoning: II. A review and recommendations. Ther Apher 2000 Aug; 4 (4): 308-12.
[39] Langer M, Vesconi S, Iapichino G, Costantino D, Radrizzani D. [The early removal of amatoxins in the treatment of amanita phalloides poisoning (author's transl)] [German] Klin Wochenschr 1980 Feb 1; 58 (3): 117-23.
[40] Sabeel AI, Kurkus J, Lindholm T. Intensive hemodialysis and hemoperfusion treatment of Amanita mushroom poisoning. Mycopathologia 1995 Aug; 131 (2): 107-14.
[41] Wauters JP, Rossel C, Farquet JJ. Amanita phalloides poisoning treated by early charcoal haemoperfusion. Br Med J 1978 Nov 25; 2 (6150): 1465.
[42] Aji DY, Caliskan S, Nayir A, Mat A, Can B, Yasar Z, Ozsahin H, Cullu F, Sever L. Haemoperfusion in Amanita phalloides poisoning. J Trop Pediatr 1995 Dec; 41 (6): 371-4.
[43] Mullins ME, Horowitz BZ. The futility of hemoperfusion and hemodialysis in Amanita phalloides poisoning. Vet Hum Toxicol 2000 Apr; 42 (2): 90-1.
[44] Feinfeld DA, Mofenson HC, Caraccio T, Kee M. Poisoning by amatoxin-containing mushrooms in suburban New York--report of four cases. J Toxicol Clin Toxicol 1994; 32 (6): 715-21.
[45] Nicholls DW, Hyne BE, Buchanan P. Death cap mushroom poisoning. [Letter] N Z Med J 1995 Jun 14; 108 (1001): 234.
[46] Cappell MS, Hassan T. Gastrointestinal and hepatic effects of Amanita phalloides ingestion. J Clin Gastroenterol 1992 Oct; 15 (3): 225-8.
[47] Woodle ES, Moody RR, Cox KL, Cannon RA, Ward RE. Orthotopic liver transplantation in a patient with Amanita poisoning. JAMA 1985 Jan 4; 253 (1): 69-70.
[48] Lim JG, Kim JH, Lee CY, Lee SI, Kim YS. Amanita virosa induced toxic hepatitis: report of three cases. Yonsei Med J 2000 Jun; 41 (3): 416-21.
[49] Ganzert M, Felgenhauer N, Zilker T. Indication of liver transplantation following amatoxin intoxication. J Hepatol 2005 Feb; 42 (2): 202-9.
[50] Kelner MJ, Alexander NM. Endocrine hormone abnormalities in Amanita poisoning. J Toxicol Clin Toxicol 1987; 25 (1-2): 21-37.
[51] Nicholson FB, Korman MG. Death from Amanita poisoning. [Letter] Aust N Z J Med 1997 Aug; 27 (4): 448-9.
[52] Bivins HG, Knopp R, Lammers R, McMicken DB, Wolowodiuk O. Mushroom ingestion. Ann Emerg Med 1985 Nov; 14 (11): 1099-104.
[53] Ramirez P, Parrilla P, Sanchez Bueno F, Robles R, Pons JA, Bixquert V, Nicolas S, Nunez R, Alegria MS, Miras M. Fulminant hepatic failure after Lepiota mushroom poisoning. J Hepatol 1993 Aug; 19 (1): 51-4.
[54] Benjamin DR. Mushrooms: poisons and panaceas: a handbook for naturalists, mycologists, and physicians. New York: WH Freeman and Company; 1995. p. 198-241.
[55] Floersheim GL, Weber O, Tschumi P, Ulbrich M. [Clinical death-cap (Amanita phalloides) poisoning: prognostic factors and therapeutic measures. Analysis of 205 cases] [German] Schweiz Med Wochenschr 1982 Aug 21; 112 (34): 1164-77.
[56] Pond SM, Olson KR, Woo OF, Osterloh JD, Ward RE, Kaufman DA, Moody RR. Amatoxin poisoning in northern California, 1982-1983. West J Med 1986 Aug; 145 (2): 204-9.
[57] Piqueras J. Hepatotoxic mushroom poisoning: diagnosis and management. Mycopathologia 1989 Feb; 105 (2): 99-110.
[58] Jander S, Bischoff J. Treatment of Amanita phalloides poisoning: I. Retrospective evaluation of plasmapheresis in 21 patients. Ther Apher 2000 Aug; 4 (4): 303-7.
[59] Giannini L, Vannacci A, Missanelli A, Mastroianni R, Mannaioni PF, Moroni F, Masini E. Amatoxin poisoning: A 15-year retrospective analysis and follow-up evaluation of 105 patients. Clin Toxicol (Phila) 2007; 45 (5): 539-42.
[60] Scheurlen C, Spannbrucker N, Spengler U, Zachoval R, Schulte-Witte H, Brensing KA, Sauerbruch T. Amanita phalloides intoxications in a family of russian immigrants. Case reports and review of the literature with a focus on orthotopic liver transplantation. Z Gastroenterol 1994 Jul; 32 (7): 399-404.
[61] Escudie L, Francoz C, Vinel JP, Moucari R, Cournot M, Paradis V, Sauvanet A, Belghiti J, Valla D, Bernuau J, Durand F. Amanita phalloides poisoning: Reassessment of prognostic factors and indications for emergency liver transplantation. J Hepatol 2007 Mar; 46 (3): 466-73.
[62] Fineschi V, Di Paolo M, Centini F. Histological criteria for diagnosis of amanita phalloides poisoning. J Forensic Sci 1996 May; 41 (3): 429-32.
[63] Yocum RR. New laboratory scale purification of beta-amanitin from American Amanita phalloides. Biochemistry 1978 Sep 5; 17 (18): 3786-9.
[64] Trim GM, Lepp H, Hall MJ, McKeown RV, McCaughan GW, Duggin GG, Le Couteur DG. Poisoning by Amanita phalloides ("deathcap") mushrooms in the Australian Capital Territory. Med J Aust 1999 Sep 6; 171 (5): 247-9.
[65] Omidynia E, Rashidpourai R, Qaderi MT, Ameri E. Mycetismus in Hamadan, of west Iran. Southeast Asian J Trop Med Public Health 1997 Jun; 28 (2): 438-9.
[66] Teutsch C, Brennan RW. Amanita mushroom poisoning with recovery from coma: a case report. Ann Neurol 1978 Feb; 3 (2): 177-9.
[67] Klein AS, Hart J, Brems JJ, Goldstein L, Lewin K, Busuttil RW. Amanita poisoning: treatment and the role of liver transplantation. Am J Med 1989 Feb; 86 (2): 187-93.
[68] Olson KR, Pond SM, Seward J, Healey K, Woo OF, Becker CE. Amanita phalloides-type mushroom poisoning. West J Med 1982 Oct; 137 (4): 282-9.
[69] Broussard CN, Aggarwal A, Lacey SR, Post AB, Gramlich T, Henderson JM, Younossi ZM. Mushroom poisoning--from diarrhea to liver transplantation. Am J Gastroenterol 2001 Nov; 96 (11): 3195-8.
[70] Meunier BC, Camus CM, Houssin DP, Messner MJ, Gerault AM, Launois BG. Liver transplantation after severe poisoning due to amatoxin-containing Lepiota--report of three cases. J Toxicol Clin Toxicol 1995; 33 (2): 165-71.
[71] Langer M, Gridelli B, Piccolo G, Markovic S, Quarenghi E, Gatti S, Ghio L, Ginevri F. A liver transplant candidate (fulminant hepatic failure from amanita phalloides poisoning) as a multiorgan donor. Transplant Proc 1997 Dec; 29 (8): 3343-4.
[72] Unverir P, Soner BC, Dedeoglu E, Karcioglu O, Boztok K, Tuncok Y. Renal and hepatic injury with elevated cardiac enzymes in Amanita phalloides poisoning: a case report. Hum Exp Toxicol 2007 Sep; 26 (9): 757-61.
[73] Piering WF, Bratanow N. Role of the clinical laboratory in guiding treatment of Amanita virosa mushroom poisoning: report of two cases. Clin Chem 1990 Mar; 36 (3): 571-4.
[74] Alves A, Gouveia Ferreira M, Paulo J, Franca A, Carvalho A. Mushroom poisoning with Amanita phalloides - a report of four cases. Eur J Intern Med 2001 Feb; 12 (1): 64-66.
[75] Rosenthal P, Roberts JP, Ascher NL, Emond JC. Auxiliary liver transplant in fulminant failure. Pediatrics 1997 Aug; 100 (2): E10.
[76] Das RN, Parajuli S, Jayakumar J. "Last supper with mushroom soup": a case report of amatoxin poisoning. Mcgill J Med 2007 Jul; 10 (2): 93-5.
[77] Serne EH, Toorians AW, Gietema JA, Bronsveld W, Haagsma EB, Mulder PO. Amanita phalloides, a potentially lethal mushroom: its clinical presentation and therapeutic options. Neth J Med 1996 Jul; 49 (1): 19-23.
[78] Himmelmann A, Mang G, Schnorf-Huber S. Lethal ingestion of stored Amanita phalloides mushrooms. Swiss Med Wkly 2001 Oct 20; 131 (41-42): 616-7.
[79] Sanz P, Reig R, Borras L, Martinez J, Manez R, Corbella J. Disseminated intravascular coagulation and mesenteric venous thrombosis in fatal Amanita poisoning. Hum Toxicol 1988 Mar; 7 (2): 199-201.
[80] Amanita phalloides mushroom poisoning--Northern California, January 1997. MMWR Morb Mortal Wkly Rep 1997 Jun 6; 46 (22): 489-92.
[81] Wieland T. Poisonous principles of mushrooms of the genus Amanita. Four-carbon amines acting on the central nervous system and cell-destroying cyclic peptides are produced. Science 1968 Mar 1; 159 (818): 946-52.
[82] Haines JH, Lichstein E, Glickerman D. A fatal poisoning from an amatoxin containing Lepiota. Mycopathologia 1986 Jan; 93 (1): 15-7.
[83] Wieland T, Faulstich H. Amatoxins, phallotoxins, phallolysin, and antamanide: the biologically active components of poisonous Amanita mushrooms. CRC Crit Rev Biochem 1978 Dec; 5 (3): 185-260.
[84] Belliardo F, Massano G, Accomo S. Amatoxins do not cross the placental barrier. [Letter] Lancet 1983 Jun 18; 1 (8338): 1381.
[85] Nagy I, Pogatsa-Murray G, Zalanyi S Jr, Komlosi P, Laszlo F, Ungi I. Amanita poisoning during the second trimester of pregnancy. A case report and a review of the literature. Clin Investig 1994 Oct; 72 (10): 794-8.
[86] Dolfi F, Gonnella R. [Acute amanita phalloides poisoning in the second pregnancy trimester] [Italian] Minerva Anestesiol 1994 Mar; 60 (3): 153-4.
[87] Timar L, Czeizel AE. Birth weight and congenital anomalies following poisonous mushroom intoxication during pregnancy. Reprod Toxicol 1997 Nov-Dec; 11 (6): 861-6.
[88] Schleufe P, Seidel C. [Amanita poisoning during pregnancy] [German] Anasthesiol Intensivmed Notfallmed Schmerzther 2003 Nov; 38 (11): 716-8.
[89] Kaufmann M, Muller A, Paweletz N, Haller U, Kubli F. [Fetal damage due to mushroom poisoning with amanita phalloides during the first trimester of pregnancy (author's transl)] [German] Geburtshilfe Frauenheilkd 1978 Feb; 38 (2): 122-4.
[90] Vetter J. Toxins of Amanita phalloides. Toxicon 1998 Jan; 36 (1): 13-24.
[91] Faulstich H. New aspects of amanita poisoning. Klin Wochenschr 1979 Nov 2; 57 (21): 1143-52.
[92] Zanotti G, Petersen G, Wieland T. Structure-toxicity relationships in the amatoxin series. Structural variations of side chain 3 and inhibition of RNA polymerase II. Int J Pept Protein Res 1992 Dec; 40 (6): 551-8.
[93] Estes JE, Selden LA, Gershman LC. Mechanism of action of phalloidin on the polymerization of muscle actin. Biochemistry 1981 Feb 17; 20 (4): 708-12.
[94] Wieland T, Govindan VM. Phallotoxins bind to actins. FEBS Lett 1974 Sep 15; 46 (1): 351-3.
[95] Dancker P, Low I, Hasselbach W, Wieland T. Interaction of actin with phalloidin: polymerization and stabilization of F-actin. Biochim Biophys Acta 1975 Aug 19; 400 (2): 407-14.
[96] Gicquaud C, Turcotte A, Gruda J, Tuchweber B. [In vivo and in vitro effects of peptide extracts from Amanita virosa] [French] Rev Can Biol Exp 1982 Mar; 41 (1): 23-34.
[97] Pastorello L, Tolentino D, D'Alterio M, Paladino R, Frigerio A, Bergamo N, Valli A. Determination of alpha-amanitin by high-performance liquid chromatography. J Chromatogr 1982 Dec 10; 233 (): 398-403.
[98] Jaeger A, Jehl F, Flesch F, Sauder P, Kopferschmitt J. Kinetics of amatoxins in human poisoning: therapeutic implications. J Toxicol Clin Toxicol 1993; 31 (1): 63-80.
[99] Butera R, Locatelli C, Coccini T, Manzo L. Diagnostic accuracy of urinary amanitin in suspected mushroom poisoning: a pilot study. J Toxicol Clin Toxicol 2004; 42 (6): 901-12.
[100] Homann J, Heinrich D, Wizemann V, Matthes KJ. [Should the therapy in Amanita phalloides poisoning really be changed?] [German] [Letter] Dtsch Med Wochenschr 1983 Sep 23; 108 (38): 1455-6.
[101] Faulstich H, Talas A, Wellhoner HH. Toxicokinetics of labeled amatoxins in the dog. Arch Toxicol 1985 Jan; 56 (3): 190-4.
[102] Fiume L, Sperti S, Montanaro L, Busi C, Costantino D. Amanitins do not bind to serum albumin. [Letter] Lancet 1977 May 21; 1 (8021): 1111.
[103] Budavari S, editor. The Merck index. 12th ed. Whitehouse Station (NJ): Merck & Co; 1996. p. 64-5.
[104] Bresinsky A, Besl H. A colour atlas of poisonous fungi. London: Wolfe Publishing Ltd; 1990. p. 18-24.

Do Not Archive.

This document is current on day of issue,
NZ: 22.Nov.2017

Disclaimer

All information contained on this database is as accurate and up-to-date as our resources allow. Since the University of Otago, the New Zealand National Poisons Centre and Intergen cannot anticipate or control the conditions under which this information may be used, each user should view the information in the specific context of the intended application.

The University of Otago, the New Zealand National Poisons Centre and Intergen will not be responsible for damages of any nature resulting from use or reliance upon this information.

© National Poisons Centre, New Zealand. Portions © Intergen.

If you would like further information about TOXINZ, or wish to make comment, please contact us on +64 3 479 7248 or email us at TOXINZ@otago.ac.nz.