Maxwell Moor-Smith, BSc, Raymond Li, BSc(Pharm), MSc, Omar Ahmad, MD, FRCPC The world’s most poisonous mushroom, Amanita phalloides, is growing in BC The expanded range of death cap mushrooms—previously found on the roots of imported European trees but now found in association with native Garry oaks—puts amateur foragers at risk, and recognition of amatoxin poisoning is essential to preventing future fatalities. ABSTRACT: Amatoxins in Amanita acute liver failure occurs. Manage- shown some benefit in a retro- phalloides, commonly known as the ment of the symptomatic patient spective survival analysis. With the death cap mushroom, are responsi- consists of providing supportive expanded range of A. phalloides in ble for 90% of the world’s mushroom- care, promoting renal elimination of BC, physicians should be alert to related fatalities. The most deadly amatoxins, interrupting enterohe- the possibility of amatoxin poison- amatoxin for humans is α-amanitin, patic recirculation of amatoxins, and ing and include it in the differential a bicyclic octapeptide that irrevers- administering proposed antidotes. diagnosis of a patient presenting ibly binds RNA polymerase II, thus Although no established antidote with gastroenteritis or hepatotoxic- preventing protein synthesis and for A. phalloides has been identified, ity and a history of ingesting foraged causing cell death. Three recent N-acetylcysteine and silibinin have mushrooms. poisoning cases in British Columbia show how the death cap can be eas- ily mistaken for edible mushrooms the world’s most poisonous mushroom such as the puffball and the paddy is growing in British Columbia straw mushroom. Since being intro- duced from Europe to the west and mid-Atlantic coasts of North Ameri- Amanita phalloides, commonly known as the death cap mushroom, ca, A. phalloides has spread to south is responsible for 90% of the world’s mushroom-related fatalities. coastal BC, and has the potential to spread to vast areas of the continent. Following ingestion of A. phalloides, CliniCal presentation is triphasiC: there is a latency period (6 hours) followed by intoxication, classically described as triphasic: a dysentery phase (6 to 24 hours), a false recov- 6–24 24–72 4–9 ery phase (24 to 72 hours), and a HOURS HOURS DAYS hepatorenal phase (4 to 9 days) con- Dysentery phase False recovery phase hepatorenal phase sisting of multisystem organ failure, seizures, coma, and death. Management of symptomatic patients includes supportive measures, promoting Treatment is based on decontami- renal elimination of amatoxins, and early consultation with a liver transplant centre. nation and liver transplantation if Maxwell Moor-smith, Bsc, raymond li, Msc, omar ahmad, MD This article has been peer reviewed. BCMJ 2019;61:20-24 20 BC MEDICAL JOURNAL VOL. 61 NO. 1, JANUARY/FEBRUARY 2019 bcmj.org The world’s most poisonous mushroom, Amanita phalloides, is growing in BC manita phalloides, known tion of A. phalloides in North Amer- As an ectomycorrhizal fungus, A. commonly as the death cap ica was in northern California at the phalloides forms an obligate symbiot- A mushroom, causes life- Hotel Del Monte in 1935, a location ic relationship with the roots of trees, threatening hepatorenal dysfunction famous for its exotic and unusual gar- which have been mostly nonnative, when ingested. Considered the most dens.5 Since then, the death cap has broad-leaf trees.4,5 This association poisonous mushroom in the world, been introduced to multiple sites in may have limited the mushroom’s A. phalloides contains amatoxins, a the Pacific Northwest. spread so far. However, in Victoria group of bicyclic octapeptides that A. phalloides specimens were first A. phalloides has now been found in are responsible for 90% of global collected in BC in 1997 from under association with native BC Garry oak mushroom-related fatalities. One cap European chestnut trees at Lake Er- trees, which may allow the mushroom of A. phalloides is sufficient to cause rock in the upper Fraser Valley. The to expand its range even further.4 death in an adult.1-3 first identification of A. phalloides Pringle and colleagues estimate the The death cap was first introduced in Victoria was in 1998 from under speed of A. phalloides spread among to British Columbia on the roots of a large European beech tree on the native California coastal oak at 5 imported European trees and has landscaped grounds of Government km per year on average (range 3 to since spread to North American oak House, the residence of BC’s lieu- 9 km/year).5 Additionally, predictive trees.4,5 Death caps are now found in- tenant governor. A. phalloides was climate suitability mapping shows creasingly in urban settings. In 2017 detected in Vancouver in 2008 under that most of south coastal BC is ap- the Canadian Forest Service and Oak European hornbeam trees that had propriate habitat for A. phalloides5 Bay parks department reported that been planted by the city in the 1960s.4 ( Figure 1 ). death caps in the Victoria area sprout- Since these first specimens were Mushroom foragers and health ed earlier and in greater numbers than collected, there have been numer- care providers should be aware of the in previous years.6 The spread of this ous reports of A. phalloides found in expanded range for this highly toxic invasive species has led to cases of Vancouver and the Fraser Valley, on mushroom in order to prevent fatali- morbidity and mortality from inges- Southern Vancouver Island, and on ties from the death cap in the future.7 tion of the mushroom and an ongoing the Gulf Islands. risk of misidentification. Health care providers need to be aware of this risk, as prompt recognition and ap- propriate management are critical for positive patient outcomes. Distribution A. phalloides is not native to North America. First identified in Europe, the species has now traveled to Aus- tralia, Asia, Southern Africa, and the Americas on the roots of imported trees.5 The first confirmed collec- Mr Moor-Smith is a medical student (class of 2020) in the University of British Colum- bia Island Medical Program. Mr Li is a drug Death cap mushroom, Amanita phalloides and poison information pharmacist at the Known location, single site BC Drug and Poison Information Centre. Dr Known location, multiple sites Ahmad is a physician with Island Health and Potential distribution head of Critical Care and Emergency Medi- cine. He is also a clinical associate profes- Figure 1. Amanita phalloides distribution in BC. sor in the Department of Emergency Medi- Map: © Province of British Columbia. All rights reserved. Reproduced with permission of the Province cine at the University of British Columbia. of British Columbia. Image: Adolf Ceska, used with permission. BC MEDICAL JOURNAL VOL. 61 NO. 1, JANUARY/FEBRUARY 2019 bcmj.org 21 The world’s most poisonous mushroom, Amanita phalloides, is growing in BC Identification and misidentification A. phalloides typically grows from June to November in BC and looks different depending on its stage of maturity. The immature mushroom may be totally encased in a “univer- sal veil,” giving it the egg-like ap- pearance of a puffball mushroom if not cut in half to reveal the growing mushroom inside. As the mushroom Figure 2. Amanita phalloides specimens at various stages of growth. matures, the universal veil ruptures Image: Paul Kroeger, used with permission. and remains in the ground as a mem- branous sac (volva). The cap may binds RNA polymerase II, thus pre- ized by abdominal pain, vomiting, and grow up to 16 cm in diameter, becom- venting protein synthesis and caus- severe, cholera-like diarrhea that may ing broad and slightly convex. The ing cell death. None of the amatoxins contain blood and mucus, and often cap can be white or have a green or are destroyed by cooking, drying, results in profound dehydration.2,10 yellow hue, and is often darker in the or freezing. The presence of organic The second (false recovery) phase centre. A. phalloides specimens typ- anion transporting polypeptide 1B3 occurs 24 to 72 hours after ingestion ically feature white gills and spores, (OATP1B3) in hepatic sinusoidal with the patient demonstrating symp- a ring of tissue (annulus) near the top membranes results in the active trans- tomatic improvement despite clinical of the stalk, and a volva at the base8 port of toxin into hepatocytes, causing signs and biochemical markers of liv- ( Figure 2 ). massive centrilobular necrosis and er damage progressing, peaking at 60 Death caps can easily be misiden- vascular degeneration.2,9 Amatoxins to 72 hours after ingestion.11 The third tified as an edible variety of mush- are primarily eliminated by renal ex- (hepatorenal) phase occurs 4 to 9 days room, as seen in three cases of cretion, with a portion undergoing after ingestion and is characterized by amateur foragers who mistook the biliary excretion and enterohepatic acute liver and multisystem organ death cap for other species. In 2003 recirculation.9 The kidneys may also failure that can lead to convulsions, a 43-year-old man in Victoria con- be affected and show signs of acute hemorrhage, coma, and death.2,3 sumed an immature death cap he tubular necrosis and hyaline casts in thought was a puffball mushroom. In the tubules.2 Diagnosis and 2008 a 63-year-old woman in Van- management couver consumed a mature death cap Triphasic clinical Amatoxin mushroom poisoning can she assumed was a paddy straw mush- presentation be fatal. The best prognosis results room, a common variety in Asia but Symptoms following the ingestion from prompt recognition and appro- one not native to North America. Both of nonfatal mushroom species gener- priate management. The foundation patients recovered following hospital- ally occur within 6 hours. In contrast, of diagnosis is an accurate history and ization.