Journal of college of Medical Sciences-Nepal, 2010, Vol.6, No-2, 56-61 Book Review Mushroom Poisoning-an overview

B. S. Patowary Professor, Department of Medicine, College of Medical Sciences, Bharatpur, Nepal

Abstract There are many thousands of mushroom species in the world, some are edible and some are poisonous due to containing significant toxins. The edible mushroom is a common food item with tempting flavour, taste and nutritive value; nowadays quite often grown at home and cultured with commercial marketing. Mushroom poisoning usually results from ingestion of wild mushrooms due to misidentification of a toxic mushroom as an edible species bearing very close resemblance, deliberate seeking of psychotropic mushrooms and accidental childhood ingestions. Majority of fatal mushroom poisoning occurs due to ingestion of Amanita Phalloides - the ‘death cap’, due to its high content of Amatoxin – a potent cytotoxin. Fatal poisoning is usually associated with delayed onset of symptoms which are very severe, with hepatic, renal, hemolytic and CNS involvement. Aim of this article is for informational and preventive purpose.

Key words: Mushroom poisoning, amanita phalloidis, amatoxin.

Mushroom poisoning refers to deleterious effects The characteristic pathologic finding in fatalities from ingestion of toxic substances present in a from amatoxin containing mushroom poisoning is acute mushroom. The toxins present are secondary massive necrosis of liver parenchyma.1 Hemolysis and metabolites produced in specific biochemical pathways renal failure are common accompaniments with in the fungal cell. Majority of fatal poisoning worldwide occasional pancreatitis. are attributable to the Amanita Phalloides mushroom Mushroom poisoning is usually the result of ingestion – appropriately named "death cap"; other dangerous of wild mushrooms due to misidentification of a toxic species of mushrooms are Amanita verna, Amanita mushroom as an edible species bearing close virosa , Gyromitra, Gallerina and Lepiota species – all resemblance. It is also found as a result of small of which contain amatoxin , a potent cytotoxin. children, specially toddlers in the ‘grazing’ stage Ingestion of even a portion of one mushroom of a ingesting mushrooms found in the lawn. "Magic" dangerous species may be sufficient to cause death. mushrooms are intentionally taken by adolescents for The lethal dose of Amatoxin is ~ 10mg, the amount their hallucinogenic effects.2 found in a single death cap mushroom.1 The clinical manifestations of mushroom poisoning depend mainly on the type of mushroom involved (the degree of toxic species) , amount ingested (obvious), Correspondences: Dr. B. S. Patowary age (symptoms in children are more fatal compared to E-mail: drbspatowary @ yahoo.com 56 B. S. Patowary, Mushroom Poisoning-an overview an adult due to their having low body weight), time of Kinetics of amatoxin – it rapidly disappears from onset of symptoms (very toxic mushroom poisoning plasma, excreted in urine during first few days cases usually have delayed onset of symptoms which following ingestion; large amount may be eliminated in are very severe with hepatic, renal, hemolytic and CNS faeces. involvement), geographic distribution (some of the dangerous species of mushrooms could be more 1. Phallotoxin – also a hepatic toxin and gastro – abundant in some locations; also some specimen that intestinal irritant. look edible at one geographic location may be deadly 2.Amanita haemolysin – a hemolytic glycoside that in another region) as well as premorbid hepatic and breaks down RBCs. renal condition. Amatoxin is also present in other mushrooms3 viz. A verna, A virosa and Galerina. Lapiota species is highly Toxins and their manifestations toxic and is associated with a fatality rate of about 20%4 The clinical manifestations of mushroom poisoning and in children, it is higher. are dependent on the fungal species involved. These may range from minor gastro – intestinal disturbances Clinical manifestations of amatoxin poisoning to hallucinations, delirium, cramps and even fatal They are briefed as this is the most fatal toxin. consequences. The highest reported incidences of mushroom The manifestations occur in different stages or phases.4 poisoning and fatality are due to consumption of These include: Amanita Phalloides. This mushroom produces different toxins.3 1. A characteristic latent period of 6-24 hours post ingestion before onset of symptoms. 1.Amatoxin (alpha, beta and gamma amanitins ) – a 2. Then abdominal cramping, nausea, vomiting and thermostable nitrogenous bicyclic octapeptide insoluble severe watery diarrhoea occur that usually in water. It irreversibly binds to and inhibits RNA Last for 24 hours; fluid losses may be severe enough polymerase II, blocking the production of DNA ,the to cause profound dehydration, even circulatory basis of cell reproduction; this leads to the death of collapse. many cells specially those that reproduce frequently 3. A period of remission of symptoms occurs that last e.g liver, intestine, kidneys and ultimately the CNS. 1-3 days (if hospitalised, the patient is sometimes It binds to the muscle protein actin – essential for released).However on going liver damage is muscle contraction, thus delaying the ability of certain occurring as indicated by laboratory investigations muscle groups to contract, resulting in weakness. (elevation of serum amino transferase levels, It produces acute liver failure, producing extensive prothrombin time). Hepatic and renal injury become parenchymal necrosis as well as renal failure and clinically apparent and may progress to fulminant occasionally pancreatic toxicity. It is eight fold more hepatic failure and renal failure. toxic than Phallotoxin. 57 Journal of college of Medical Sciences-Nepal, 2010, Vol.6, No-2 Death occurs within 3-7 days or recovery within 2-3 there will be appearance of a blue colour if weeks. amatoxin is present. Adverse prognostic criteria in acute liver 3. An experienced mycologist may analyse and failure2 identify spores in gastric contents.3 A regional 1. Prothrombin time > 100 sec toxicology centre may be informed. Or 4. High performance liquid chromatography for Any three of the following detection of amatoxin from plasma, faeces, urine i) Prothrombin time > 50 sec. or vomits to be done if facilities are available. ii) S. Bilirubin level: >300 µmol/L(H"17.6 mg/dl) iii) S. Creatinine :>300 µmol/L(H"3.38 mg/dl) Differential diagnosis iv) Jaundice to encephalopathy time < 7 days 1. Gastroenteritis v) Age < 10 yrs or > 40 yrs 2. Plant poisoning from different species or 3. Hypovolumic shock and Factor V level of < 15% of normal and 4. Other causes of acute liver and renal failure encephalopathy grade 3 or 4 (marked confusion / coma) Management These criteria predict a mortality rate of > 90%. 1. Pre- hospital care- Institute supportive measures if needed viz. I.V. access and Oxygen and induce Diagnosis of mushroom poisoning vomiting. 1. From clinical features, a positive history of If a mushroom sample is available, place it in a dry mushroom intake is present. Symptoms may be paper bag (do not moisten or refrigerate) for a mild and early, when the mushroom species is less mycologist to identify. toxic, amount ingested is less and single species is 2. Emergency department care – aggressively treat a consumed: but when different species of patient with suspected mushroom ingestion as the mushrooms are ingested, early symptoms do not mortality of ingested amatoxin is very high – about 4 exclude delayed and fatal complications of a very 20 % . 4 toxic species. Very toxic mushroom poisoning 3. Reduction of amatoxin absorption. cases usually have delayed onset of symptoms, Consider gastric lavage if the patient has not already often with hepatic, hemolytic, renal and CNS vomited. Lavage should be attempted within 1 hour of involvement. ingestion. Given the delayed presentation, efficacy of 2. If a specimen of the ingested mushroom is found, this procedure is uncertain as patient becomes analysis for amatoxins done by a Maixner test3 - symptomatic and seek medical attention usually after by expressing a drop of liquid from the specimen a delay of 12 hours or more. on a paper, containing wood pulp e.g. news However, give repeated doses of activated charcoal orally for any recent ingestion of an unidentified or paper, allowed to dry and placing a drop of 10- potentially toxic mushroom. Amatoxin appear to 12 N HCL on this spot. After several minutes, 58 B. S. Patowary, Mushroom Poisoning-an overview undergo entero - hepatic circulation, repeat dose b) Silibinin/ sylimarin: a potent anti – oxidant, prevents activated charcoal and laxatives may interrupt this cycle free radical damage and amatoxin uptake by liver and reduce toxicity. Gastroduodenal aspiration may cells. Early administration (within 48 hours) may be done to remove the toxins eliminated in bile and be an effective measure. Dose 20 mg/kg/over 24 interrupt this cycle and reduce toxicity. hours given in four 2 hours infusions. Mainstay of treatment include aggressive c) Thioctic acid – clinical efficacy not yet proven. intravenous fluids and electrolytes; to correct and d) Cimetidine – it is a cytochrome P 450 inhibitor. maintain adequate hydration and urinary out put as well e) Vit.K – if coagulopathy is present as intensive supportive care for hepatic failure. f) N-Acetylcysteine – not definitely proved. It improves cerebral blood flow and oxygenation in Laboratory Studies patients with fulminant hepatitis due to any cause. • Obtain liver function tests, as hepatic damage g) Corticosteroids – not proved. is the main concern in Amatoxin poisoning. Hemodialysis–to remove mushroom poison early. It -Prothrombin time (PT): most reliable indicator for has become a part of the treatment programme in the severity of poisoning. United States along with other schedules. -Amino transferase levels For fulminant hepatic failure – consult for liver -Alkaline Phosphatase level transplantation as liver transplant can save the life4 of a -Bilirubin level patient with most severe amatoxin poisoning. • Complete blood count, glucose level • Electrolytes, Blood Urea, S. Creatinine level Criteria for transplantation5 (dehydration from vomiting, diarrhoea) A prolonged Prothrombin time ( a measure of blood • Urine analysis ( Proteinuria and haematuria clotting) signify renal involvement) Elevated levels of liver enzymes (indicative of liver • Amylase / Lipase level ( Pancreatitis) dysfunction) • Urinary amanitin analysis (if facilities available) Increased levels of ammonia in blood. Antidotes: Several have been proposed, but none have Other symptoms eg. Hepatic encephalopathy (Gr. II proven to be of clinical efficacy as controlled studies –III) are lacking and experimental data in animals are When the interval between ingestion and the onset of equivocal.4 diarrhoea is <8 hours a) Benzylpenicillin (Penicillin G): Based on the or hypothesis that in liver failure due to Amanita, The INR is > 6.0 even in the absence of GABA derived from enteric bacteria may be encephalopathy. insufficiently metabolized; high dose Penicillin is used to sterilize and reduce the GABA – producing When indicated, the operation should proceed as soon intestinal flora and may prevent the severe as possible, before the effects of liver failure become encephalopathy likely to be the final cause of death more widespread. : Dose upto 1 millon U/kg/ day I.V.

59 Journal of college of Medical Sciences-Nepal, 2010, Vol.6, No-2 Discussion drying or other means of food preparations. It is best No adequate database exists to estimate the to avoid alcohol while consuming mushroom. It is worldwide exposure and fatality due to mushroom worth remembering that there is no specific antidote poisoning. for lethal mushroom poisoning. Patients with severe hepatitis from mushroom If there is suspicion of consuming a poisonous poisoning are thought to have a poor prognosis and mushroom, immediately a physician /hospital to be frequently need liver transplantation for survival. But contacted or to approach a local poison control center with early and aggressive multidisciplinary care, such for the needful. patients have improved outcome and may avoid liver Aiming at primary prevention, the government should transplantation, as suggested by Rengstorff et al, 2003.6 establish regional toxicology centers which would From San Francisco, USA, from their retrospective impart public education on recognition of toxic study of 8 admitted patients over 5 year period - all mushroom along with first aid management. the 8 patients survived; even though 3 had developed Every physician should consider amanita toxicity in the encephalopathy ( grade I to III) , and 1 developed differential diagnosis of acute hepatic and renal failure, acute renal failure requiring hemodialysis. In another especially in high prevalent regions. 15 – years retro spective analysis and follow up evaluation of 105 patients from Florence, Italie ( Acknowledgement Giannini et al, 2007)7 deaths have been recorded only I offer my thanks to Mr. Ajay Baruah and Mrs. in 2 patients admitted 60 hours after mushroom Sumitra Neupane for their timely help with the ingestion, while the rests recovered completely without computer. sequalae and all of them were treated within 36 hours after mushroom ingestion – none of them had liver References transplantation. Again, a 20 year retrospective analysis 1. Jules L D. Toxic and Drug Induced Hepatitis. Dennis L. of treatment of amatoxin poisoning in 2108 hospitalized Kasper , Anthony S. Fauci , Dan L. Longo et al. patients from North America and Europe (Enjalbert et Harrison’s Principles of Internal Medicine: Mc Graw- 8 al, 2002) documented little efficacy of Penicillin G, Hill. 17th ed. Newyork: McGraw-Hill; 2008: 1949-51. thioctic acid or steroids, they observed that silybin, 2. Jones A L, Karalliedde L.Poisoning. Davidson’s N-acetyl cysteine and detoxication procedures were Principles & Practice of Medicine. 20th ed. New Delhi: efficacious. Churchill Livingstone Elsevier; 2006: 952-3.

3. Litovitz T L, Smilkstein M, Felberg L et al. 1996 annual Prevention report of the American Association of Poison Control Most important factor is not to eat wild or uncultivated Centers Toxic Exposure Surveillance System. Am J Emerg mushroom as it is very difficult to correctly identify Med. 1997; 15: 447-500. edible from poisonous mushroom. It is important to 4. Kent R. Poisoning. Stephen J, Maxine A. Current remember that most lethal mushroom toxins are not Medical Diagnosis & Treatment. 47th ed. Newyork: destroyed or deactivated by cooking, canning, freezing, McGraw-Hill Lange; 2008: 1378-9.

60 B. S. Patowary, Mushroom Poisoning-an overview

5. Pinson C W, Daya M R, Benner K G et al. Liver 7. Giannini L, Vannacci A, Missanelli A et al. Amatoxin transplantation for severe Amanita Phalloides mushroom poisoning: A 15-year retrospective analysis and follow- poisoning. Am. J. Surg 1990; 159: 493-9. up evaluation of 105 patients. J Clinical toxicology, 2007; 45: 539-42. 6. Rengstorff D S, Osorio R W, Bonacini M. Recovery from severe hepatitis caused by mushroom poisoning 8. Enjalbert F, Rapior S, Nouguier Soule et al. Treatment of without liver transplantation. J. Clin Gastroenterol amatoxin poisoning: 20-year retrospective analysis. J. Hepatol 2003;1: 392-6. Clin. Toxicol. 2002; 40: 715-57.

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