Amatoxin-containing mushroom poisoning (eg, Amanita phalloides): Clinical manifestations, diagnosis, and treatment
- Tamas R Peredy, MD, FACEP, FACMT
Tamas R Peredy, MD, FACEP, FACMT
- Medical Director
- Florida Poison Information Center (FPIC) - Tampa
- Section Editors
- Michele M Burns, MD, MPH
Michele M Burns, MD, MPH
- Section Editor — Pediatric Toxicology
- Assistant Professor of Pediatrics and Emergency Medicine
- Harvard Medical School
- Stephen J Traub, MD
Stephen J Traub, MD
- Section Editor — Toxicology
- Associate Professor of Emergency Medicine
- Mayo Medical School
- Deputy Editor
- James F Wiley, II, MD, MPH
James F Wiley, II, MD, MPH
- Senior Deputy Editor — UpToDate
- Deputy Editor — Adult and Pediatric Emergency Medicine
- Deputy Editor — Primary Care Sports Medicine (Adolescents and Adults)
- Clinical Professor of Pediatrics and Emergency Medicine/Traumatology
- University of Connecticut School of Medicine
The clinical manifestations, diagnosis, and treatment of amatoxin-containing mushroom poisoning will be reviewed here.
Clinical manifestations, diagnosis, and management of poisoning caused by other types of mushroom toxins are presented separately. (See "Clinical manifestations and evaluation of mushroom poisoning" and "Management of mushroom poisoning" and "Amanita smithiana mushroom poisoning".)
More than 35 mushroom species across three genera (Amanita, Galerina, and Lepiota) contain amatoxin [1-3]. Amatoxin-containing mushrooms (eg, Amanita phalloides (picture 1 and figure 1), A. virosa, A. bisporigera (picture 2), Galerina autumnalis) cause approximately 50 deaths annually in Europe and Asia compared with a few deaths annually in the United States [1,4-8]. This difference in frequency of lethal exposures reflects the relative popularity of mushroom foraging in Europe and Asia rather than significant variance in intrinsic toxicity or prevalence of harmful mushroom species among the regions.
When serious toxicity due to mushroom ingestion does occur, it typically results from consumption of a meal of misidentified mushrooms by foraging adults and others who shared their food [2,9]. Amatoxins are not removed by boiling or otherwise cooking the mushroom. A common scenario involves amateur mushroom hunters or recent immigrants who mistake a toxic mushroom for an edible variety with similar morphologic features (eg, Amanita species (picture 1 and picture 2 and figure 1) mistaken for Agaricus species). (See "Clinical manifestations and evaluation of mushroom poisoning", section on 'Epidemiology'.)
By contrast, pediatric exposures to amatoxin-containing mushroom exposures (picture 1 and picture 2), rarely cause serious toxicity because of the limited amount of toxins available in the small amount of mushroom typically ingested. In the United States, no pediatric fatalities due to ingestion of a single mushroom have been reported in over 25 years of National Poison Data System surveillance .To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Enjalbert F, Rapior S, Nouguier-Soulé J, et al. Treatment of amatoxin poisoning: 20-year retrospective analysis. J Toxicol Clin Toxicol 2002; 40:715.
- Varvenne D, Retornaz K, Metge P, et al. Amatoxin-containing mushroom (Lepiota brunneoincarnata) familial poisoning. Pediatr Emerg Care 2015; 31:277.
- Paydas S, Kocak R, Erturk F, et al. Poisoning due to amatoxin-containing Lepiota species. Br J Clin Pract 1990; 44:450.
- Berger KJ, Guss DA. Mycotoxins revisited: Part I. J Emerg Med 2005; 28:53.
- Broussard CN, Aggarwal A, Lacey SR, et al. Mushroom poisoning--from diarrhea to liver transplantation. Am J Gastroenterol 2001; 96:3195.
- Chaiear K, Limpaiboon R, Meechai C, Poovorawan Y. Fatal mushroom poisoning caused by Amanita virosa in Thailand. Southeast Asian J Trop Med Public Health 1999; 30:157.
- Iliev Y, Andonova S, Akabaliev V. Our experience in the treatment of acute Amanita phalloides poisoning. Folia Med (Plovdiv) 1999; 41:30.
- Mowry JB, Spyker DA, Brooks DE, et al. 2014 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 32nd Annual Report. Clin Toxicol (Phila) 2015; 53:962.
- Vo KT, Montgomery ME, Mitchell ST, et al. Amanita phalloides Mushroom Poisonings - Northern California, December 2016. MMWR Morb Mortal Wkly Rep 2017; 66:549.
- American Association of Poison Control Centers. Annual reports. http://www.aapcc.org/annual-reports/ (Accessed on October 19, 2016).
- Wieland T, Faulstich H. Amatoxins, phallotoxins, phallolysin, and antamanide: the biologically active components of poisonous Amanita mushrooms. CRC Crit Rev Biochem 1978; 5:185.
- Vetter J. Toxins of Amanita phalloides. Toxicon 1998; 36:13.
- Gundala S, Wells LD, Milliano MT, et al. The hepatocellular bile acid transporter Ntcp facilitates uptake of the lethal mushroom toxin alpha-amanitin. Arch Toxicol 2004; 78:68.
- Kullak-Ublick GA, Stieger B, Meier PJ. Enterohepatic bile salt transporters in normal physiology and liver disease. Gastroenterology 2004; 126:322.
- Letschert K, Faulstich H, Keller D, Keppler D. Molecular characterization and inhibition of amanitin uptake into human hepatocytes. Toxicol Sci 2006; 91:140.
- Jaeger A, Jehl F, Flesch F, et al. Kinetics of amatoxins in human poisoning: therapeutic implications. J Toxicol Clin Toxicol 1993; 31:63.
- Feinfeld DA, Rosenberg JW, Winchester JF. Three controversial issues in extracorporeal toxin removal. Semin Dial 2006; 19:358.
- Magdalan J, Ostrowska A, Piotrowska A, et al. alpha-Amanitin induced apoptosis in primary cultured dog hepatocytes. Folia Histochem Cytobiol 2010; 48:58.
- Pond SM, Olson KR, Woo OF, et al. Amatoxin poisoning in northern California, 1982-1983. West J Med 1986; 145:204.
- Garcia J, Costa VM, Carvalho AT, et al. A breakthrough on Amanita phalloides poisoning: an effective antidotal effect by polymyxin B. Arch Toxicol 2015; 89:2305.
- Boyer JC, Hernandez F, Estorc J, et al. Management of maternal Amanita phalloïdes poisoning during the first trimester of pregnancy: a case report and review of the literature. Clin Chem 2001; 47:971.
- Chibishev A, Perevska Z, Simonovska N, et al. Severe mushroom poisoning in one Macedonian family. Int J Artif Organs 2015; 38:425.
- Diaz JH. Syndromic diagnosis and management of confirmed mushroom poisonings. Crit Care Med 2005; 33:427.
- Giannini L, Vannacci A, Missanelli A, et al. Amatoxin poisoning: a 15-year retrospective analysis and follow-up evaluation of 105 patients. Clin Toxicol (Phila) 2007; 45:539.
- Poucheret P, Fons F, Doré JC, et al. Amatoxin poisoning treatment decision-making: pharmaco-therapeutic clinical strategy assessment using multidimensional multivariate statistic analysis. Toxicon 2010; 55:1338.
- Goldfrank LR. Mushrooms. In: Goldfrank's Toxicologic Emergencies, 9th ed, Nelson LW, Lewin NA, Howland MA, et al (Eds), McGraw-Hill, New York 2011. p.1522.
- Parant F, Peltier L, Lardet G, et al. [Phalloidin syndrome: role of Elisa-based assay for the detection of alpha- and gamma-amanitins in urine. Preliminary results]. Acta Clin Belg 2006; 61 Suppl 1:11.
- 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; 42:901.
- Floersheim GL. Treatment of human amatoxin mushroom poisoning. Myths and advances in therapy. Med Toxicol 1987; 2:1.
- Karvellas CJ, Tillman H, Leung AA, et al. Acute liver injury and acute liver failure from mushroom poisoning in North America. Liver Int 2016; 36:1043.
- Bergis D, Friedrich-Rust M, Zeuzem S, et al. Treatment of Amanita phalloides intoxication by fractionated plasma separation and adsorption (Prometheus®). J Gastrointestin Liver Dis 2012; 21:171.
- Shi Y, He J, Chen S, et al. MARS: optimistic therapy method in fulminant hepatic failure secondary to cytotoxic mushroom poisoning--a case report. Liver 2002; 22 Suppl 2:78.
- Lionte C, Sorodoc L, Simionescu V. Successful treatment of an adult with Amanita phalloides-induced fulminant liver failure with molecular adsorbent recirculating system (MARS). Rom J Gastroenterol 2005; 14:267.
- Zhang J, Zhang Y, Peng Z, et al. Experience of Treatments of Amanita phalloides-Induced Fulminant Liver Failure with Molecular Adsorbent Recirculating System and Therapeutic Plasma Exchange. ASAIO J 2014; 60:407.
- Köppel C. Clinical symptomatology and management of mushroom poisoning. Toxicon 1993; 31:1513.
- Piqueras J, Duran-Suarez JR, Massuet L, Hernandez-Sanchez JM. Mushroom poisoning: therapeutic apheresis or forced diuresis. Transfusion 1987; 27:116.
- Vesconi S, Langer M, Iapichino G, et al. Therapy of cytotoxic mushroom intoxication. Crit Care Med 1985; 13:402.
- Wauters JP, Rossel C, Farquet JJ. Amanita phalloides poisoning treated by early charcoal haemoperfusion. Br Med J 1978; 2:1465.
- Ganzert M, Felgenhauer N, Schuster T, et al. [Amanita poisoning--comparison of silibinin with a combination of silibinin and penicillin]. Dtsch Med Wochenschr 2008; 133:2261.
- Mitchell, ST. New Comprehensive Amatoxin Mushroom Poisoning (AMP) Treatment Protocol. Clin Tox 2010; 48:628.
- Legalon SIL Mushroom Poisoning Clinical Study. Madaus Inc. https://sites.google.com/site/legalonsil/home (Accessed on October 18, 2016).
- Manufacturer package insert http://sites.google.com/site/legalonsil/ (Accessed on March 21, 2011).
- Mengs U, Pohl RT, Mitchell T. Legalon® SIL: the antidote of choice in patients with acute hepatotoxicity from amatoxin poisoning. Curr Pharm Biotechnol 2012; 13:1964.
- Magdalan J, Ostrowska A, Piotrowska A, et al. Benzylpenicillin, acetylcysteine and silibinin as antidotes in human hepatocytes intoxicated with alpha-amanitin. Exp Toxicol Pathol 2010; 62:367.
- Saller R, Meier R, Brignoli R. The use of silymarin in the treatment of liver diseases. Drugs 2001; 61:2035.
- Floersheim GL, Eberhard M, Tschumi P, Duckert F. Effects of penicillin and silymarin on liver enzymes and blood clotting factors in dogs given a boiled preparation of Amanita phalloides. Toxicol Appl Pharmacol 1978; 46:455.
- Floersheim GL, Schneeberger J, Bucher K. Curative potencies of penicillin in experimental Amanita phalloides poisoning. Agents Actions 1971; 2:138.
- Rainone F. Milk thistle. Am Fam Physician 2005; 72:1285.
- Wen Z, Dumas TE, Schrieber SJ, et al. Pharmacokinetics and metabolic profile of free, conjugated, and total silymarin flavonolignans in human plasma after oral administration of milk thistle extract. Drug Metab Dispos 2008; 36:65.
- Pradhan SC, Girish C. Hepatoprotective herbal drug, silymarin from experimental pharmacology to clinical medicine. Indian J Med Res 2006; 124:491.
- Desplaces A, Choppin J, Vogel G, Trost W. The effects of silymarin on experimental phalloidine poisoning. Arzneimittelforschung 1975; 25:89.
- Salmi HA, Sarna S. Effect of silymarin on chemical, functional, and morphological alterations of the liver. A double-blind controlled study. Scand J Gastroenterol 1982; 17:517.
- Magdalan J, Ostrowska A, Piotrowska A, et al. Failure of benzylpenicillin, N-acetylcysteine and silibinin to reduce alpha-amanitin hepatotoxicity. In Vivo 2009; 23:393.
- Wills BK, Haller NA, Peter D, White LJ. Use of amifostine, a novel cytoprotective, in alpha-amanitin poisoning. Clin Toxicol (Phila) 2005; 43:261.
- Faulstich H, Kirchner K, Derenzini M. Strongly enhanced toxicity of the mushroom toxin alpha-amanitin by an amatoxin-specific Fab or monoclonal antibody. Toxicon 1988; 26:491.
- Faybik P, Hetz H, Baker A, et al. Extracorporeal albumin dialysis in patients with Amanita phalloides poisoning. Liver Int 2003; 23 Suppl 3:28.
- 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.
- Faraj W, Dar F, Bartlett A, et al. Auxiliary liver transplantation for acute liver failure in children. Ann Surg 2010; 251:351.
- Grabhorn E, Nielsen D, Hillebrand G, et al. Successful outcome of severe Amanita phalloides poisoning in children. Pediatr Transplant 2013; 17:550.
- Ganzert M, Felgenhauer N, Zilker T. Indication of liver transplantation following amatoxin intoxication. J Hepatol 2005; 42:202.
- Escudié L, Francoz C, Vinel JP, et al. Amanita phalloides poisoning: reassessment of prognostic factors and indications for emergency liver transplantation. J Hepatol 2007; 46:466.
- Chang LM, Yun HS, Kim YS, Ahn JW. Aucubin: potential antidote for alpha-amanitin poisoning. J Toxicol Clin Toxicol 1984; 22:77.
- Chang IM. Liver-protective activities of aucubin derived from traditional oriental medicine. Res Commun Mol Pathol Pharmacol 1998; 102:189.
- AMATOXIN-CONTAINING MUSHROOMS
- PATHOPHYSIOLOGY AND TOXICOKINETICS
- CLINICAL MANIFESTATIONS
- DIFFERENTIAL DIAGNOSIS
- Gastroenteritis with delayed hepatotoxicity
- - Supportive care
- - Gastrointestinal decontamination
- - Elimination enhancement
- - Amatoxin uptake inhibitors
- Silibinin dihemisuccinate
- Penicillin G
- Oral milk thistle products
- - Antioxidant therapy
- Cimetidine and vitamin C
- Liver transplantation
- Experimental therapies
- ADDITIONAL RESOURCES
- SUMMARY AND RECOMMENDATIONS