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Management of Poisoning by Unknown Fungi

GENERAL APPROACH TO THE POISONED PATIENT
   1. Stabilization and complete patient evaluation
   2. Fungus identification
   3. Reduction of absorption
   4. Enhancement of elimination
SPECIFIC APPROACH TO THE POISONED PATIENT
   5. Specific fungal antidotes
   6. Main fungal syndromes and their treatment
      (i) Cyclopeptides
      (ii) Orellanine-Orelline
      (iii) Gyromitrin-Monomethylhydrazine (MMH)
      (iv) Coprine
      (v) Muscarine
      (vi) Ibotenic Acid-Muscimol
      (vii) Hallucinogenic compounds (including psilocybin, psilocin, baeocystin)
      (viii) Gastrointestinal irritants
      (ix) Other fungal toxins
FOLLOW-UP AND CONTINUING CARE OF THE POISONED PATIENT
   7. Continuing care.
    MANAGEMENT OF POISONING BY UNKNOWN FUNGI

    This guideline is intended to be only the basic set of instructions to
    manage cases of unknown mushroom  ingestion, and is by no means
    exclusive.  There may be exceptions to the guidelines contained, and
    the user should refer to the individual PIMs, other treatment guides,
    or more detailed literature for specific management of poisoning cases
    due to mushrooms which have been identified.

    Specific antidotal therapy is available for very few intoxications by
    fungi, therefore mainstays of treating poisoning are: decontamination,
    symptomatic and/or supportive therapy, clinical observation and good
    nursing care.

    GENERAL APPROACH TO THE POISONED PATIENT

    1.  Stabilization and complete patient evaluation

    Apply general clinical measures to prevent further deterioration of
    the patient.  Fortunately, poisoning by fungi is NOT a frequent
    life-threatening situation, but if airway, breathing or circulation
    are compromised, perform appropriate resuscitative measures.  The
    primary survey of the patient should be carried out simultaneously
    with resuscitation in case of life-threatening poisoning.  After
    stabilization of the vital signs, an accurate history helps guide
    further management.

    Routine questions should include:

    *    what fungus/fungi did you intend to collect
    *    what type of tree was it growing near
    *    was it growing in the woods or in the field or the garden
    *    on what substrate was the fungus growing
    *    did the fungus have an odor, what was the size and
         colour, were there gills or "sponge"
    *    how many species of fungi were consumed
    *    how many persons ate the fungus
    *    was the fungus eaten at more than one meal (what
         were the exact times of ingestion)
    *    how long after exposure did the symptoms begin to appear
    *    how was the fungus prepared (raw  vs. cooked)
    *    how were the fungi stored between collection and the 
         time of preparation
    *    how were the already prepared fungi stored before
         ingestion
    *    was any alcohol consumed with the meal
    *    are all people ill who consumed the fungus
    *    are there other ill persons in the group who did NOT
         consume the fungi
    *    did the patient ever eat this fungus before
    *    were the mushrooms bought, and if so, where.

    If the mushrooms are available and the diagnosis is still unclear, try
    to have them analysed by a mycologist, but start treatment without
    delay if serious poisoning is suspected.

    In some places the "newspaper" test (the newspaper must contain
    lignin) is being used: press the mushroom on the newspaper, let it dry
    and add one drop of hydrochloric acid.  The paper may then turn to a
    blue or bluish-green colour indicating the presence of amatoxins.  The
    test is not 100% conclusive.

    2.  Fungus identification

    Accurate identification of the fungus involved (genus and species)
    helps guide appropriate treatment.  In managing the patient poisoned
    by a fungus, it is mainly more important what the fungus is NOT,
    rather than what it is.  There are only a few fungal species in which
    the toxin (e.g. cyclopeptides, orellanine, gyromitrin) is of such a
    magnitude that the treatment of the patient must be more than only
    symptomatic in nature.  If available, a trained mycologist should be
    consulted to help eliminate from consideration the more toxic fungal
    species.

    3.  Reduction of absorption

    The mainstay in the reduction of absorption is the administration of
    activated charcoal.  Since it only takes a few minutes to adsorb
    toxins, it should be administered even before gastric lavage or emesis
    is induced (dosage: 50 to 100 g in adults, 10 to 25 g in children). 
    In general emesis or lavage only removes about one-third of ingested
    material, so sufficient activated charcoal administration should prove
    more effective.  If microscopic analysis of gastric contents is to be
    performed, do the sampling, if possible, before administration of a
    charcoal.

    4.  Enhancement of elimination

    Dialysis and haemoperfusion may be indicated only in very few fungal
    intoxications (e.g. by cyclopeptides, orellanine), but to be effective
    it must be undertaken on an early stage of poisoning.

    SPECIFIC APPROACH TO THE POISONED PATIENT

    5.  Specific fungal antidotes

    Few antidotes are available for fungal intoxications.  Many proposed
    antidotes have NOT been proven to be useful in controlled clinical
    studies, but still have their international proponents.

    6.  Main fungal syndromes and their treatment

    Symptomatic treatment of the patient should begin before
    identification of the fungus in question.  Knowledge of certain
    syndromes characteristic of fungal poisoning is important.  Always
    keep in mind that there can be many causes of symptoms which are NOT
    directly related to an exogenous fungal toxin: panic reactions (fear
    of having ingested a highly poisonous fungus), difficulties to digest
    the fungi, bacterial contamination (Salmonella, Staphylococcus, in the
    worst botulism), raw fungi (many edible species give arise to
    gastrointestinal symptoms if not prepared properly), individualized
    allergic reactions or, rarely, pesticide residues.

    It must be remembered that when dealing with fungal toxins, that the
    longer the time interval (usually > 6 to 12 hours) between ingestion
    and the onset of symptoms, the more severe the type of fungal toxin
    (e.g. amatoxin, orellanine, gyromitrin).  Long onset indicates the
    possibility of a severe poisoning.

    (i) Cyclopeptides

    These are a group of major fungal toxins, accounting for approximately
    90% of the fungal fatalities internationally.  The fatality rate in
    untreated cases is between 20 and 30%.  Patients show a relatively
    long time interval, that goes from 6 to 24 hours, between exposure and
    onset of symptoms.  Multiple dose activated charcoal is warranted in
    an attempt to interrupt the entero-hepatic recycling that can occur
    with these toxins.  Enhanced diuresis and the possibility of using
    specific antidotes could be considered.  Patients generally pass
    through four phases: (1) latent asymptomatic period, (2)
    gastro-intestinal phase with massive diarrhoea, vomiting, and
    dehydration with metabolic consequences like metabolic acidosis and
    hypoglycemia, (3) lessening of symptoms with a period of apparent
    well-being, and (4) hepatic phase (normally starting 36 to 48 hours
    after ingestion) with a rise in liver enzymes and acute hepatic
    failure. Patients who might have been exposed to these fungal toxins,
    will need close monitoring for liver damage and possible kidney
    damage,  and could possibly require a liver transplant in the most
    severe cases.  The principle is that unless these cyclopeptide
    containing fungi can NOT be ruled out from consideration in the case,
    it must be assumed that this is what the medical treatment team is
    facing.

    Example fungi: Amanita bisporigera, Amanita ocreata, Amanita
    phalloides, Amanita virosa, Amanita verna, Gallerinaspp.,
    Lepiota josserandii, Lepiota subincarnata and others; see PIM
    on amatoxin containing mushrooms.

    (ii) Orellanine-Orelline

    Cases of orellanine poisoning have been confirmed only in Europe. The
    toxin is mainly nephrotoxic with a very long delay (3 to 11 days)
    between exposure and onset of renal symptoms. Occasionally there may
    be mild gastrointestinal symptoms during the latency period.  The
    toxin is probably a bipyridyl oxide (orellanine).

    The mortality rate is thought to be approximately 15%.  Patients
    usually present with: myalgia, particularly lumbar pain, headache,
    chills, rigors, a severe burning thirst and  oliguria.  On admission
    to hospital (often after several days post ingestion) the patients
    show signs of renal damage that may progress into complete renal
    failure.

    Treatment is mainly symptomatic, but if the patient is admitted to
    hospital within 24 hours after the meal (very unusual),
    gastrointestinal decontamination and hemodialysis should be performed
    in an attempt to eliminate the toxin.

    Example fungi: Cortinarius gentilis, Cortinarius orellanus,
    Cortinarius semisanguineus, Cortinarius specciossimus  and
    others .

    (iii) Gyromitrin-Monomethylhydrazine (MMH)

    The fungal toxin gyrometrin, yields upon hydrolysis the toxic compound
    monomethylhydrazine (MMH).  The toxin has a boiling point of 87.5o C,
    and as it may be distilled off during the cooking process, it may
    produce a toxic atmosphere for the cook.  Once again, the relatively
    long onset of symptoms (6 to 12 hours) indicates that it may be a
    severe poisoning.  The intoxication is characterized by some initial
    effects: fatigue, dizziness, vertigo, severe headache, a feeling of
    bloatness, abdominal pain, and possibly emesis.  In more serious cases
    convulsions, coma, hemolysis and acute hepatitis may occur. 
    Pyridoxine (Vitamin B6) is the antidote for life-threatening symptoms 
    such as convulsions and coma.  Otherwise treatment is symptomatic and
    supportive.  Not all individuals who consume this fungus may develop
    symptoms, as each person has their own individualized tolerance, below
    which there are no visible symptoms.

    Example fungi: Gyromitra esculenta, Gyromitra gigas, Gyromitra
    infula and others; see PIM gyromitrin containing mushrooms.

    (iv) Coprine

    The fungal toxin coprine, blocks the enzyme acetaldehyde
    dehydrogenase, which stops  the metabolism of ethanol at the
    acetaldehyde stage.  It acts very similar to the drug disulfiram used
    in the treatment of alcoholism.  If ethanol is NOT consumed with the
    meal, these fungi may be edible.  Onset of symptoms is generally short
    (30 minutes to 1 hour).  The symptoms which generally only appear if
    ethanol has been consumed with the meal or within 24 hours after the
    meal, consist of: skin flushing, anxiety, a feeling of swelling or
    paresthesia in hands and feet, nausea, vomiting, a metallic taste,
    tachycardia, and chest pain.  Treatment is symptomatic and supportive,
    and remission takes place in a few hours.

    Example fungi: Coprinus atramentarius, Coprinus insignis,
    Coprinus quadrificus  and others .

    (v) Muscarine

    The fungal toxin muscarine, is physiologically very similar to the
    neurotransmitter acetylcholine, and therefore causes a cholinergic
    syndrome.  The onset of symptoms is usually short (30 minutes to 2
    hours), and consists of perspiration, salivation, and lacrimation,
    along with blurring of vision, abdominal cramps, loose-watery stools,
    flushing of the skin, miosis, hypotension, and bradycardia. 
    Bronchorrea and bronchoconstriction may also be observed.  Atropine is
    the drug of choice for the treatment of cholinergic symptoms.

    Example fungi: Clitocybe spp., Inocybe spp., Mycena
    pura and others; see PIM on muscarine containing mushrooms.

    (vi) Ibotenic Acid-Muscimol

    The fungal toxin ibotenic acid and its reduction product muscimol, are
    compounds that act on the nervous system as agonists of
    gamma-aminobutyric acid ( GABA).  Central nervous symptoms may
    alternate between depression and stimulation.  Symptoms appear after
    30 to 90 minutes after ingestion and include drowsiness, confusion,
    dizzines, euphoria, but may proceed to CNS excitation with agitation,
    illusions and manic excitement.  Seizures are observed primarily in
    children.  Muscle jerks, fasciculations and muscle spasm in the
    extremities are observed.  Treatment is symptomatic and supportive. 
    For anxiety, agitation and convulsions benzodiazepines may be useful. 
    Although one would think that the species named  muscaria implies
    that muscarine is the main toxic agent found in the mushrooms, it is
    only present in small amounts.

    Example fungi: Amanita cothurnata, Amanita muscaria, Amanita
    pantherina and others; see PIM Isoxazole containing mushrooms.

    (vii) Hallucinogenic compounds (including psilocybin,
    psilocin, baeocystin)

    These fungal compounds affect the central nervous system, causing
    LSD-like symptoms. Usually after 30 to 60 minutes post exposure, the
    patient will exhibit: laughter, confusion, disorientation,
    depersonalization, derealization, visual and auditory hallucinations,
    hyperkinetic compulsive movements.  Treatment is symptomatic and
    supportive, in a quiet environment, talk-down therapy, and sedation
    when necessary.  NOTE: Fungi sold on the street as substances of
    abuse, may be either hallucinogenic fungi, or may have been
    adulterated with other mind-altering compounds, or merely have no
    mind-altering potential at all.

    Example fungi: Gymnopilus spp., Panaeolus spp ., Psilocybe spp.
    and others ; see PIM on Psilocybin containing mushrooms.

    (viii) Gastrointestinal irritants

    These fungal toxins are a collection of as yet mostly unidentified
    compounds which seem to cause most of their symptomatology in the
    gastro-intestinal tract: nausea, vomiting, diarrhea. Onset of symptoms
    is generally short (30 minutes to 2 hours).  Treatment is symptomatic
    and supportive.

    Example fungi: Agaricus hondensis, Boletus eastwoodiae, Boletus
    frostii, Boletus satanus, Enteloma luridus, Hebeloma
    crustiliniforme, Lactarius torminosus, Omphalotus olearius,
    Paxillus involutus, Pholiota squarrosa, Ramaria formosa,
    Russula emetica, Scleroderma aurantium, Verpa bohemica  and
    others .

    (ix) Other fungal toxins

    More research is required on other fungal toxins which seem to be
    associated with some  unique toxic syndromes.  Some of the fungi which
    have been implicated with toxic syndromes include: Amanita
    smithiana  and A. proxima (renal failure), Auricularia
    auricula (easy bruising and excessive bleeding), Hypholoma
    fasiculare (hepatic injury), Paxillus involutus (immune
    hemolytic anemia), Clitocybe acromelalga , Lepiota inversa,
    Clitocybes amaenoens (erythromelalgia, paresthesia and dysesthesia
    remaining for over one year - personal communication from J.
    Trestrail).
    

    FOLLOW-UP AND CONTINUING CARE OF THE POISONED PATIENT

    7.  Continuing care.

    After diagnosis and initial treatment, an adequate observation period
    should be established, especially if the poisoning is severe.

    Psychiatric evaluation and counseling is indicated in the case of
    intentional poisoning (e.g. suicide, substance abuse).

    Education is recommended in cases of accidental poisoning by fungi, in
    order to prevent further poisoning incidents. 

    Prevention and educational material is available in a number of
    poisons centres.



    Author:

    John H. Trestrail, III, RPh. FAACT, DABAT
    Toxicologist
    Grand Rapids, Michigan, USA

    Date: August 30, 2000


    Reviewed by:

    Luc De Haro, Heinz Faulstich, Barbara Groszek, John Haines, Jonas
    Hojer, Christine Karlson-Stiber, Hans Persson, Jenny Pronczuk, John H.
    Trestrail III, Thomas Zilker.
    Stockholm, Sweden, 21st October, 2000
    Erfurt, Germany, 9th November, 2000
    





















    See Also:
       Toxicological Abbreviations