Amanita bisporigera

Drawing of Amanita mushrooms showing the volva at the base and the ring on the stem.

Bookmark and Share


September 2007 | Back to Table of Contents

Clinical and Health Affairs

Amanita bisporigera

By Manu Madhok, M.D., M.P.H.

Ingestion and Death from Mistaken Identity

Abstract
A triphasic onset of subacute gastrointestinal toxicity, followed by a false recovery period, and, subsequently, late-onset hepatic failure is pathogenomonic of poisoning with cyclopeptide-containing Amanita mushrooms. This article presents the case report of 7 Minnesota residents who developed symptoms of Amanita poisoning after consuming cooked mushrooms picked at a county park. The article includes a review of the pathophysiology and management of Amanita poisoning.



On September 14, 2006, the Minnesota Department of Health (MDH) issued a press release reporting 7 members of the Hmong community being hospitalized after consuming wild mushrooms picked at a park in Ramsey County 5 days earlier.1 All 7 family members had consumed the mushrooms for dinner and presented at a local emergency room with severe vomiting, abdominal cramps, and diarrhea in the early morning hours of September 10, which was approximately 6 to 8 hours post ingestion. Three were hospitalized, and 4 were treated and released.

The index case was a previously healthy 10-year-old girl who had ingested an unknown quantity of mushroom soup at 10 p.m. on September 9. She subsequently awoke around 4 a.m. (September 10) with intense abdominal pain and nonbilious and nonbloody vomiting. The patient presented to a local emergency department with gastrointestinal symptoms that evening. The child denied having diarrhea, dizziness, vision changes, or neurologic symptoms. On examination, she had no apparent distress. Her weight was 66 kg, blood pressure 103/64, pulse 119, respiration 16, temperature 36.6 degrees C. Abdominal examination showed diffuse tenderness but no guarding or rigidity; bowel sounds were present. There was no icterus or sign of chronic liver disease. The remaining findings on examination were within normal limits.

Laboratory testing included serum electrolytes (sodium 140, potassium 4.8, chloride 110, bicarbonate 18, BUN 20, creatinine 1.1, glucose 116), a liver panel (AST 51, ALT 66, alkaline phosphatase 262, total bilirubin 0.3, direct bilirubin 0.1, total protein 8.5, albumin 5.1), and a complete blood count (CBC) (white blood cell count 22,500, hemoglobin 16.2g/dL, and platelets 429,000).

The girl’s family brought 1 of the harvested mushrooms to the emergency room, and a local mycologist identified it as Amanita bisporigera.

After intravenous normal saline bolus and consultation with the Minnesota Poison Control Center, the patient was transferred to Children’s Hospitals and Clinics in St. Paul, where she received activated charcoal, mucomyst, high-dose penicillin G, cimetidine, vitamin E, and selenium. Laboratory studies were repeated 4 hours later (nearly 24 hours post ingestion). They revealed elevated liver enzymes (AST 114, ALT 109, alkaline phosphatase 858, PT 13.5 sec, PTT 35 sec, international normalized ratio [INR] 1.02), ammonia 29, electrolytes (sodium 137, potassium 5.5, chloride 103, bicarbonate 20, BUN 19, creatinine 0.7), and unchanged CBC (white blood cell count 23,000, hemoglobin 15.9g/dL, and platelets 472,000). Upon consultation with gastroenterology and in light of mounting liver enzymes over the next 6 hours (AST 378, ALT 345), the girl was transferred to an intensive care unit at the University of Minnesota Medical Center in the event she would need a liver transplant. She appeared stable over the next 24 hours and was transferred to a pediatric floor. She decompensated rapidly, developing multiple organ failure, despite maximal supportive care, and died 6 days after consuming the mushrooms.

Pathophysiology of Amanita Poisoning 2-6
Amanita bisporigera and related species are beautiful-but-deadly mushrooms found in the Midwest and Pacific Northwest in late summer and fall. The white fungi have a pair of distinctive features: a cup-like volva at the base and a ring on the stem. Unfortunately, people who gather mushrooms for the table sometimes mistake Amanita bisporigera for edible mushrooms, as they look similar to the paddy straw mushrooms that grow in Southeast Asia and the Volvariella speciosa of North America. Confusion arises when the ring on the stem of an Amanita mushroom gets rubbed off and the volva is buried at the soil surface, making it difficult to distinguish from the other varieties.

The fruiting body of Amanita bisporigera mushrooms contains alpha- and beta-amatoxins, a subgroup of toxins found in Amanita genus and other mushroom species. Alpha-amanitin and beta-amanitin are cyclopeptides of 8 amino acids and are possibly the most deadly of all the amatoxins. Amatoxins are heat-stable, insoluble in water, and not destroyed by drying or cooking.

Approximately 0.2 mg to 0.4 mg of amatoxin can be obtained from 1 g of mushroom. The lethal dose of the amatoxin is less than 0.1 mg/kg body weight.3 The toxin is absorbed in the small intestine, and 60% of the absorbed alpha-amanitin is excreted into bile and undergoes enterohepatic circulation. The kidney clears 40%.

Alpha-amanitin inhibits RNA polymerase II, thereby interfering with DNA transcription, which suppresses RNA production and protein synthesis. This causes cellular necrosis, especially in cells that are initially exposed and have rapid rates of protein synthesis. This process results in severe acute liver dysfunction and ultimately hepatic failure.

Amanita mushroom poisoning is typically characterized by distinct stages:

Incubation. An asymptomatic period that ranges from 6 hours to 12 hours post-ingestion. (Amanita smithiana is an exception, see discussion.)

Gastrointestinal. Six hours to 16 hours after ingestion, when the patient experiences the onset of abdominal pain, explosive vomiting, and diarrhea that lasts for up to 24 hours. This may lead to dehydration, severe electrolyte imbalances, and shock. Early gastrointestinal symptoms may be related to other toxins such as phalloidin.

Cytotoxic. Twenty-four hours to 48 hours after ingestion, effects of amatoxins appear as clinical and biochemical signs of liver damage; however, the patient is free of gastrointestinal symptoms. Signs of hepatic dysfunction such as jaundice, hypoglycemia, and acidosis may begin to appear. Later, prothrombin values and ammonia levels rise, and the signs of hepatic encephalopathy and/or renal failure appear.

There are typically 2 clinical outcomes for patients who are poisoned by Amanita mushrooms: slow resolution with a decrease in liver enzyme levels and recovery of prothrombin activity or persistent increase in AST and ALT levels and low prothrombin levels, which indicate massive liver necrosis and a grave prognosis. The risk factors for mortality are being younger than 10 years of age, a short latency period between ingestion and onset of symptoms, severe coagulopathy, severe hyperbilirubinemia, and rising serum creatinine levels.

Treatment Guidelines
There is no specific antidote for amatoxins. The general principles of treatment are:

  • Vigorous fluid and electrolyte resuscitation, 
  • Removal of amatoxin from the gastrointestinal tract, 
  • Prevention of enterohepatic circulation of amatoxins, 
  • Elimination of amatoxin from blood and tissues, 
  • Protection of the liver and other organs from the toxic effects of amatoxins, and 
  • Aggressive treatment of coagulopathy and encephalopathy.7-11

Anecdotal studies provide the basis for therapeutic modalities, which include the following:

  • Multidose activated charcoal, which helps reduce absorption of the toxin. 
  • N-acetylcysteine (NAC, Mucomyst), which supplies sulfhydryl groups to act as substrate for detoxifying reactive toxic intermediates. NAC may have a direct cytoprotective effect as well.12 
  • Penicillin G, which competes with amatoxin for binding sites on serum proteins and may diminish hepatocellular toxin uptake. Penicillin may also reduce the GABA-producing intestinal flora and prevent progression of hepatic encephalopathy. 
  • Cimetidine, which inhibits cytochrome P450. Amanitins are believed to be converted to toxic metabolites by the hepatic cytochrome P450 system. 
  • Silybum marianum, a flavolignone isolated from milk thistle that may interrupt the enterohepatic circulation of amanitins. It may inhibit the binding of alpha-amanitin to hepatocytes, and it competes with amatoxin for transmembrane transport.13,14 Hepatocyte uptake of alpha-amanitin may be mediated by a liver-specific transporter, sodium-taurocholate cotransporter polypeptide (Ntcp).15 Intravenous silibinin, the water-soluble preparation of silymarin, may be useful in limiting Amanita toxicity but is unavailable in the United States. Oral silymarin has been recommended as an alternative. Milk thistle was highly effective in an animal model of Amanita poisoning and has been used in limited clinical trials in patients with acute and chronic liver disease.16 
  • Charcoal hemoperfusion/hemodialysis, which can be used to enhance elimination, especially in the presence of renal failure.17 Large amounts of toxins cannot, however, be removed because of plasma concentrations and large volume of distribution. Some newer techniques such as molecular absorbent regenerating system (MARS) dialysis have been used successfully in the treatment of children in fulminant hepatic failure as a result of toxic mushroom ingestion. MARS is a cell-free, extracorporeal liver assistance method utilizing an albumin dialysate for the removal of albumin-bound toxins such as amatoxins.18 
  • Nasobiliary drainage. Gastroduodenal aspiration has been attempted to remove biliary drainage and interrupt enterohepatic circulation. Although it may not remove all secretions, nasobiliary drainage has the theoretical advantage of completely interrupting the enterohepatic circulation of amatoxins and has proved successful in anecdotal reports. 
  • Liver transplantation. This should be considered for patients with severe hepatic necrosis, encephalopathy, and laboratory results showing prothrombin below 20% in combination with elevated creatinine (greater than 2mg/dL) and high bilirubin levels (greater than 5mg/dL).19-21

Discussion
Amanita bisporigera mushrooms can easily be mistaken for other edible mushrooms. Because they look similar to edible paddy straw mushrooms that grow in Southeast Asia, they may be mistakenly gathered by Hmong or other Southeast Asians now living in Minnesota and other parts of the United States. Most reports of Amanita intoxication originate in central Europe, where amateur mushroom hunting is commonplace; however, there have been numerous reports in the United States as well. Most mushroom fatalities worldwide continue to be caused by cyclopeptide-containing species from 3 major genera: Amanita (A. bisporigera, A. hygroscopia, A. ocreata, A. phalloides, A. suballiacea, A. tenuifolia, A. verna, A. virosa); Galerina (G. autumnalis, G. marginata, G. venenata); and Lepiota (L. brunneoincarnata, L. chlorophyllum, L. helveola, L. josserandii). Amanita phalloides, the ubiquitous Death Cap (Death Angel), is generally considered the most toxic of the world’s cyclopeptide-containing Amanita mushrooms, with Galerina species being the least toxic.7 The American Association of Poison Control Centers (AAPCC) reported 7,146 mushroom exposures in 2005, of which 40 were the result of consuming cyclopeptide-containing mushrooms. These contributed to 4 out of 6 deaths. In Minnesota in 2005-06, there were 516 mushroom exposures, of which 10 were attributed to cyclopeptide-containing mushrooms. These mushrooms were responsible for the only death that occurred as a result of mushroom poisoning.

The delayed onset of gastrointestinal symptoms, which appear between 6 hours and 16 hours after ingestion should be taken as a sign of Amanita poisoning. Note, however, that a relative of Amanita bisporigera, Amanita smithiana, which is found in the Pacific Northwest, lacks this delayed presentation.22 Amanita smithiana ingestion has been associated with gastrointestinal symptoms such as vomiting that occur as early as 30 minutes after ingestion. These patients, too, are at risk for significant nephrotoxicity.22 Patients who ingest toxic Amanita mushrooms including Amanita bisporigera should be referred to a tertiary care center with liver transplantation capability.

There is no specific antidote to the amatoxins in these mushrooms, and plasma or urine amanitin levels do not correlate with clinical severity or outcome. Thus, maximally aggressive medical therapy is recommended in cases of significant ingestion. There have been no randomized controlled trials, however, to prove the efficacy of the treatment modalities, only case reports on the use of nasobiliary drainage to interrupt the enterohepatic circulation with good outcomes.8,9

Conclusion
A thorough history and physical assessment along with accurate mycological identification are essential to the proper management of patients who have consumed poisonous mushrooms. Ingestion of white-gilled, pale-green smooth mushrooms with an onset of gastrointestinal symptoms at 6 hours to 16 hours post-ingestion are suggestive of Amanita mushroom poisoning. Aggressive supportive care and enhanced elimination are the mainstays of treatment. Community education is important to prevent such ingestion, and increasing awareness in the medical community would aid in early diagnosis and aggressive treatment. MM

Manu Madhok is an attending physician in the division of emergency medicine at Children’s Hospitals and Clinics of Minnesota and fellowship director for pediatric emergency medicine at the University of Minnesota.

References
1. Minnesota Department of Health News Release. September 14, 2006. Available at: www.health.state.mn.us/news/pressrel/mushrooms091406.html. Accessed August 22, 2007.
2. Bryson PD. Mushrooms. In: Bryson PD, ed. Comprehensive Review in Toxicology for Emergency Clinicians. 3rd ed. Washington, DC: Taylor & Francis; 1996:685-93.
3. Ellenhorn MJ. Plants-mycotoxins-mushrooms. In: Ellenhorn’s Medical Toxicology. 2nd ed. Philadelphia, PA: Williams & Wilkins, 1997:1881-96.
4. Handbook of Mushroom Poisoning, Diagnosis and Treatment. 2nd ed. Spoerke DG and Rumack BH, eds. CRC Press, 1994.
5. Vesconi S, Langer M, Lapichino G, Costantino D, Gusi C, Fiume L. Therapy of cytotoxic mushroomintoxication. Crit Care Med. 1985;13(5):402-6.
6. Cappell MS, Hassan T. Gastrointestinal and hepatic effects of Amanita phalloides ingestion. J Clin Gastroenterol. 1992;15(3): 225-8.
7. Diaz JH. Evolving global epidemiology, syndromic classification, general management, and prevention of unknown mushroom poisonings. Crit Care Med. 2005;33(2):419-26.
8. Scheurlen C, Spannbrrucker N, Spengler U, Zachoval R, Schulte-Witte H, Brensing KA, Sauerbruch T. Amanita phalloides intoxications in a family of Russian immigrants. Z Gastroenterol. 1994;32(7):399-404.
9. Madhok M, Scalzo AJ, Blume CM, Neuschwander-Tetri BA, Weber JA, Thompson MW. Amanita bisporigera ingestion: mistaken identity, dose-related toxicity, and improvement despite severe hepatotoxicity. Pediatr Emerg Care. 2006 22(3):177-80.
10. Mas A. Mushrooms, amatoxins and the liver. J Hepatol. 2005;42(2):166-9.
11. Fineschi V, Di Paolo M, Centini F: Histological criteria for diagnosis of Amanita poisoning. J Forensic Sci. 1996;41(3):429-32.
12. Montanini S, Sinardi D, Praticò 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;49(12):1044-7.
13. Castiella A, Arenas JI. Utility of silymarin in the cyclopeptide syndrome. J Hepatol. 1994;21(6):1148.
14. Vogel G, Tuchweber B, Trost W, et al. Protection by silibinin against Amanita phalloides intoxication in beagles. Toxicol Appl Pharmacol. 1984;73(3):355-62.
15. Gundala S, Wells LD, Milliano MT, Talkad V, Luxon BA, Neuschwander-Tetri BA. The hepatocellular bile acid transporter Ntcp facilitates uptake of the lethal mushroom toxin alpha-amanitin. Arch Toxicol. 2004;78(2):68-73.
16. Flora K, Hahn M, Rosen H. Milk thistle (Silybum marianum) for the therapy of liver disease. Am J Gastroenterol. 1998;93(2):139-43.
17. Sabeel AI, Kurkus J, Lindholm T. Intensive hemodialysis and hemoperfusion treatment of Amanita mushroom poisoning. Mycopathologia. 1995;131(2):107-14.
18. Covic A, Goldsmith DJ, Gusbeth-tatomir P, et al. Successful use of Molecular Absorbent Regenerating System (MARS) dialysis for the treatment of fulminant hepatic failure in children accidentally poisoned by toxic mushroom ingestion. Liver Int. 2003; 23 Suppl 3:21-7.
19. Skaare VK: Mushroom poisoning: an indication for liver transplantation. J Transpl Coord. 1997;7(3):141-3.
20. Pinson CW, Daya MR, Benner KG, et al. Liver transplantation for severe Amanita phalloides mushroom poisoning. Am J Surg. 1990;159(5):493-9.
21. Ganzert M, Felgenhauer N, Zilker T. Indication of liver transplantation following amatoxin intoxication. J Hepatol 2005;42(2):202-9.
22. Warden CR, Benjamin DR. Acute renal failure associated with suspected Amanita smithiana mushroom ingestions: a case series. Acad Emerg Med. 1998 Aug;5(8):808-12.
 Print  

. .