Management of Poisoning by Unknown Fungi

 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 specciossimusand
 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 quadrificusand 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 bohemicaand
 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