Death cap
Overview
Amanita phalloides commonly known as the death cap, is a deadly poisonous basidiomycete fungus
Fungus
A fungus is a member of a large group of eukaryotic organisms that includes microorganisms such as yeasts and molds , as well as the more familiar mushrooms. These organisms are classified as a kingdom, Fungi, which is separate from plants, animals, and bacteria...

, one of many in the genus Amanita
Amanita
The genus Amanita contains about 600 species of agarics including some of the most toxic known mushrooms found worldwide. This genus is responsible for approximately 95% of the fatalities resulting from mushroom poisoning, with the death cap accounting for about 50% on its own...

. Widely distributed across Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...

, A. phalloides forms ectomycorrhizas with various broadleaved trees. In some cases, death cap has been introduced to new regions with the cultivation of non-native species of oak
Oak
An oak is a tree or shrub in the genus Quercus , of which about 600 species exist. "Oak" may also appear in the names of species in related genera, notably Lithocarpus...

, chestnut
Chestnut
Chestnut , some species called chinkapin or chinquapin, is a genus of eight or nine species of deciduous trees and shrubs in the beech family Fagaceae, native to temperate regions of the Northern Hemisphere. The name also refers to the edible nuts they produce.-Species:The chestnut belongs to the...

, and pine. The large fruiting bodies (mushroom
Mushroom
A mushroom is the fleshy, spore-bearing fruiting body of a fungus, typically produced above ground on soil or on its food source. The standard for the name "mushroom" is the cultivated white button mushroom, Agaricus bisporus; hence the word "mushroom" is most often applied to those fungi that...

s) appear in summer and autumn; the caps
Pileus (mycology)
The pileus is the technical name for the cap, or cap-like part, of a basidiocarp or ascocarp that supports a spore-bearing surface, the hymenium. The hymenium may consist of lamellae, tubes, or teeth, on the underside of the pileus...

 are generally greenish in color, with a white stipe
Stipe (mycology)
thumb|150px|right|Diagram of a [[basidiomycete]] stipe with an [[annulus |annulus]] and [[volva |volva]]In mycology a stipe refers to the stem or stalk-like feature supporting the cap of a mushroom. Like all tissues of the mushroom other than the hymenium, the stipe is composed of sterile hyphal...

 and gills.

Coincidentally, these toxic mushrooms resemble several edible species (most notably caesar's mushroom and the straw mushroom) commonly consumed by humans, increasing the risk of accidental poison
Poison
In the context of biology, poisons are substances that can cause disturbances to organisms, usually by chemical reaction or other activity on the molecular scale, when a sufficient quantity is absorbed by an organism....

ing.
Unanswered Questions
Encyclopedia
Amanita phalloides commonly known as the death cap, is a deadly poisonous basidiomycete fungus
Fungus
A fungus is a member of a large group of eukaryotic organisms that includes microorganisms such as yeasts and molds , as well as the more familiar mushrooms. These organisms are classified as a kingdom, Fungi, which is separate from plants, animals, and bacteria...

, one of many in the genus Amanita
Amanita
The genus Amanita contains about 600 species of agarics including some of the most toxic known mushrooms found worldwide. This genus is responsible for approximately 95% of the fatalities resulting from mushroom poisoning, with the death cap accounting for about 50% on its own...

. Widely distributed across Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...

, A. phalloides forms ectomycorrhizas with various broadleaved trees. In some cases, death cap has been introduced to new regions with the cultivation of non-native species of oak
Oak
An oak is a tree or shrub in the genus Quercus , of which about 600 species exist. "Oak" may also appear in the names of species in related genera, notably Lithocarpus...

, chestnut
Chestnut
Chestnut , some species called chinkapin or chinquapin, is a genus of eight or nine species of deciduous trees and shrubs in the beech family Fagaceae, native to temperate regions of the Northern Hemisphere. The name also refers to the edible nuts they produce.-Species:The chestnut belongs to the...

, and pine. The large fruiting bodies (mushroom
Mushroom
A mushroom is the fleshy, spore-bearing fruiting body of a fungus, typically produced above ground on soil or on its food source. The standard for the name "mushroom" is the cultivated white button mushroom, Agaricus bisporus; hence the word "mushroom" is most often applied to those fungi that...

s) appear in summer and autumn; the caps
Pileus (mycology)
The pileus is the technical name for the cap, or cap-like part, of a basidiocarp or ascocarp that supports a spore-bearing surface, the hymenium. The hymenium may consist of lamellae, tubes, or teeth, on the underside of the pileus...

 are generally greenish in color, with a white stipe
Stipe (mycology)
thumb|150px|right|Diagram of a [[basidiomycete]] stipe with an [[annulus |annulus]] and [[volva |volva]]In mycology a stipe refers to the stem or stalk-like feature supporting the cap of a mushroom. Like all tissues of the mushroom other than the hymenium, the stipe is composed of sterile hyphal...

 and gills.

Coincidentally, these toxic mushrooms resemble several edible species (most notably caesar's mushroom and the straw mushroom) commonly consumed by humans, increasing the risk of accidental poison
Poison
In the context of biology, poisons are substances that can cause disturbances to organisms, usually by chemical reaction or other activity on the molecular scale, when a sufficient quantity is absorbed by an organism....

ing. A. phalloides is one of the most poisonous of all known toadstools. It has been involved in the majority of human deaths from mushroom poisoning
Mushroom poisoning
Mushroom poisoning refers to harmful effects from ingestion of toxic substances present in a mushroom. These symptoms can vary from slight gastrointestinal discomfort to death. The toxins present are secondary metabolites produced in specific biochemical pathways in the fungal cells...

, possibly including the deaths of Roman Emperor
Roman Emperor
The Roman emperor was the ruler of the Roman State during the imperial period . The Romans had no single term for the office although at any given time, a given title was associated with the emperor...

 Claudius
Claudius
Claudius , was Roman Emperor from 41 to 54. A member of the Julio-Claudian dynasty, he was the son of Drusus and Antonia Minor. He was born at Lugdunum in Gaul and was the first Roman Emperor to be born outside Italy...

 and Holy Roman Emperor
Holy Roman Emperor
The Holy Roman Emperor is a term used by historians to denote a medieval ruler who, as German King, had also received the title of "Emperor of the Romans" from the Pope...

 Charles VI
Charles VI, Holy Roman Emperor
Charles VI was the penultimate Habsburg sovereign of the Habsburg Empire. He succeeded his elder brother, Joseph I, as Holy Roman Emperor, King of Bohemia , Hungary and Croatia , Archduke of Austria, etc., in 1711...

. It has been the subject of much research, and many of its biologically active agents have been isolated. The principal toxic constituent is α-amanitin
Alpha-amanitin
alpha-Amanitin or α-amanitin is a cyclic peptide of eight amino acids. It is possibly the most deadly of all the amatoxins, toxins found in several species of the Amanita genus of mushrooms, one being the Death cap as well as the Destroying angel, a complex of similar species, principally A....

, which damages the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

 and kidneys, often fatally.

Taxonomy and naming

The death cap was first described by French botanist Sébastien Vaillant
Sébastien Vaillant
Sébastien Vaillant was a French botanist.Vaillant was born at Vigny, Val d'Oise. He studied medicine at Pontoise, and then moved to Paris to practice as a surgeon, where he studied botany at the Jardin des Plantes under Joseph Pitton de Tournefort.Vaillant was appointed to the staff of the Jardin...

 in 1727, who gave a succinct phrase name "Fungus phalloides, annulatus, sordide virescens, et patulus", which is still recognizable as the fungus today. Though the scientific name phalloides means "phallus-shaped", it is unclear whether it is named for its resemblance to a literal phallus
Phallus
A phallus is an erect penis, a penis-shaped object such as a dildo, or a mimetic image of an erect penis. Any object that symbolically resembles a penis may also be referred to as a phallus; however, such objects are more often referred to as being phallic...

 or the stinkhorn mushrooms Phallus
Phallus (genus)
The genus Phallus, commonly known as stinkhorns, are a group of basidiomycetes which produce a foul-scented, phallic mushroom, from which their name is derived. The genus has a widespread distribution and, according to a 2008 estimate, contains 18 species. They belong to the family Phallaceae in...

.
In 1821, Elias Magnus Fries
Elias Magnus Fries
-External links:*, Authors of fungal names, Mushroom, the Journal of Wild Mushrooming.*...

 described it as Agaricus phalloides, but included all white Amanitas within its description. Finally in 1833, Johann Heinrich Friedrich Link
Johann Heinrich Friedrich Link
Johann Heinrich Friedrich Link was a German naturalist and botanist.Link was born at Hildesheim as a son of the minister August Heinrich Link , who taught him the love for nature through collection of 'natural objects'...

 settled on the name Amanita phalloides, after Persoon
Christian Hendrik Persoon
Christiaan Hendrik Persoon was a mycologist who made additions to Linnaeus' mushroom taxonomy.-Early life:...

 had named it Amanita viridis thirty years earlier. Although Louis Secretan
Louis Secretan
Louis Secretan , was a Swiss lawyer and mycologist. He published Mycologie Suisse in 1833, though the names are not regarded as valid unless republished by other authors.-References:...

's use of the name Amanita phalloides predates Link's, it has been rejected for nomenclatural purposes because Secretan's works did not use binomial nomenclature
Binomial nomenclature
Binomial nomenclature is a formal system of naming species of living things by giving each a name composed of two parts, both of which use Latin grammatical forms, although they can be based on words from other languages...

 consistently; some taxonomists have, however, disagreed with this opinion.

Amanita phalloides is the type species
Type species
In biological nomenclature, a type species is both a concept and a practical system which is used in the classification and nomenclature of animals and plants. The value of a "type species" lies in the fact that it makes clear what is meant by a particular genus name. A type species is the species...

 of Amanita section
Section (botany)
In botany, a section is a taxonomic rank below the genus, but above the species. The subgenus, if present, is higher than the section, and the rank of series, if present, is below the section. Sections are typically used to help organise very large genera, which may have hundreds of species...

 Phalloideae, a group that contains all of the deadly poisonous Amanita species thus far identified. Most notable of these are the species known as destroying angel
Destroying angel
The name destroying angel applies to several similar, closely related species of deadly all-white mushrooms in the genus Amanita. They are Amanita bisporigera and A. ocreata in eastern and western North America, and A. virosa in Europe. Another very similar species, A. verna or fool's mushroom was...

s, namely Amanita virosa
Amanita virosa
Amanita virosa, commonly known as the European destroying angel, is a deadly poisonous basidiomycete fungus, one of many in the genus Amanita. Occurring in Europe, A. virosa associates with various deciduous and coniferous trees...

and Amanita bisporigera
Amanita bisporigera
Amanita bisporigera is a deadly poisonous species of fungus in the Amanitaceae family. It is commonly known as the eastern North American destroying angel or the destroying angel, although it shares this latter name with three other lethal white Amanita species, A. ocreata, A. verna and...

as well as the fool's mushroom (A. verna
Amanita verna
Amanita verna, commonly known as the fool's mushroom, Destroying angel or the mushroom fool, is a deadly poisonous basidiomycete fungus, one of many in the genus Amanita. Occurring in Europe in spring, A. verna associates with various deciduous and coniferous trees...

)
. The term "destroying angel" has been applied to A. phalloides at times, but "death cap" is by far the most common vernacular name used in English. Other common names also listed include "stinking amanita" and "deadly amanita".

A rarely appearing all-white form was initially described A. phalloides f. alba by Max Britzelmayr
Max Britzelmayr
Max Britzelmayr was a German mycologist and lichenologist who was a native of Augsburg.He spent his career as a schoolteacher and Kreisschulinspektor in Augsburg...

, though its status has been unclear. It is often found growing amid normally colored death caps. It has been described, in 2004, as a distinct variety and includes what was termed A. verna var. tarda. The true Amanita verna fruits in spring and turns yellow with KOH
Potassium hydroxide
Potassium hydroxide is an inorganic compound with the formula KOH, commonly called caustic potash.Along with sodium hydroxide , this colorless solid is a prototypical strong base. It has many industrial and niche applications. Most applications exploit its reactivity toward acids and its corrosive...

 solution, whereas A. phalloides never does.

Description

The death cap has a large and imposing epigeous (aboveground) fruiting body (basidiocarp), usually with a pileus
Pileus (mycology)
The pileus is the technical name for the cap, or cap-like part, of a basidiocarp or ascocarp that supports a spore-bearing surface, the hymenium. The hymenium may consist of lamellae, tubes, or teeth, on the underside of the pileus...

 (cap) from 5 to 15 cm (2–6 in) across, initially rounded and hemispherical, but flattening with age. The color of the cap can be pale-, yellowish-, or olive-green, often paler toward the margins and often paler after rain. The cap surface is sticky when wet and easily peeled, a troublesome feature, as that is allegedly a feature of edible fungi. The remains of the partial veil
Partial veil
thumb|150px|right|Developmental stages of [[Agaricus campestris]] showing the role and evolution of a partial veilPartial veil is a mycological term used to describe a temporary structure of tissue found on the fruiting bodies of some basidiomycete fungi, typically agarics...

 are seen as a skirtlike, floppy annulus
Annulus (mycology)
An annulus is the ring like structure sometimes found on the stipe of some species of mushrooms. The annulus represents the remaining part of the partial veil, after it has ruptured to expose the gills or other spore-producing surface. An annulus may be thick and membranous, or it may be cobweb-like...

 usually about 1 to 1.5 cm (0.4–0.6 in) below the cap. The crowded white lamellae (gills) are free. The stipe
Stipe (mycology)
thumb|150px|right|Diagram of a [[basidiomycete]] stipe with an [[annulus |annulus]] and [[volva |volva]]In mycology a stipe refers to the stem or stalk-like feature supporting the cap of a mushroom. Like all tissues of the mushroom other than the hymenium, the stipe is composed of sterile hyphal...

 is white with a scattering of grayish-olive scales and is 8 to 15 cm (3–6 in) long and 1 to 2 cm (3/8–3/4 in) thick, with a swollen, ragged, sac-like white volva
Volva (mycology)
The volva is a mycological term to describe a cup-like structure at the base of a mushroom that is a remnant of the universal veil. This macrofeature is important in wild mushroom identification due to it being an easily observed, taxonomically significant feature which frequently signifies a...

 (base). As the volva, which may be hidden by leaf litter, is a distinctive and diagnostic feature, it is important to remove some debris to check for it.

The smell has been described as initially faint and honey-sweet but strengthening over time to become overpowering, sickly-sweet and objectionable. Young specimens first emerge from the ground resembling a white egg covered by a universal veil
Universal veil
In mycology, a universal veil is a temporary membranous tissue that fully envelops immature fruiting bodies of certain gilled mushrooms. The developing Caesar's mushroom , for example, which may resemble a small white sphere at this point, is protected by this structure...

, which then breaks, leaving the volva as a remnant. The spore print
Spore print
thumb|300px|right|Making a spore print of the mushroom Volvariella volvacea shown in composite: mushroom cap laid on white and dark paper; cap removed after 24 hours showing pinkish-tan spore print...

 is white, a common feature of Amanita. The transparent spores are globular to egg-shaped, measure 8–10 μm
Micrometre
A micrometer , is by definition 1×10-6 of a meter .In plain English, it means one-millionth of a meter . Its unit symbol in the International System of Units is μm...

 (0.3–0.4 mil
Thou (unit of length)
A thou also known as a mil or point, is the verbalized abbreviation for "thousandth of an inch." It is a unit of length equal to 0.001 inch....

) long, and stain blue with iodine
Iodine
Iodine is a chemical element with the symbol I and atomic number 53. The name is pronounced , , or . The name is from the , meaning violet or purple, due to the color of elemental iodine vapor....

. The gills, on the other hand, are seen to stain pallid lilac or pink with concentrated sulfuric acid
Sulfuric acid
Sulfuric acid is a strong mineral acid with the molecular formula . Its historical name is oil of vitriol. Pure sulfuric acid is a highly corrosive, colorless, viscous liquid. The salts of sulfuric acid are called sulfates...

.

Distribution and habitat

The death cap is native to Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...

, where it is widespread. It is found from the southern coastal regions of Scandinavia
Scandinavia
Scandinavia is a cultural, historical and ethno-linguistic region in northern Europe that includes the three kingdoms of Denmark, Norway and Sweden, characterized by their common ethno-cultural heritage and language. Modern Norway and Sweden proper are situated on the Scandinavian Peninsula,...

 in the north, to Ireland
Ireland
Ireland is an island to the northwest of continental Europe. It is the third-largest island in Europe and the twentieth-largest island on Earth...

 in the west, east to Poland
Poland
Poland , officially the Republic of Poland , is a country in Central Europe bordered by Germany to the west; the Czech Republic and Slovakia to the south; Ukraine, Belarus and Lithuania to the east; and the Baltic Sea and Kaliningrad Oblast, a Russian exclave, to the north...

 and western Russia
Russia
Russia or , officially known as both Russia and the Russian Federation , is a country in northern Eurasia. It is a federal semi-presidential republic, comprising 83 federal subjects...

, and south throughout the Balkans
Balkans
The Balkans is a geopolitical and cultural region of southeastern Europe...

, in Italy
Italy
Italy , officially the Italian Republic languages]] under the European Charter for Regional or Minority Languages. In each of these, Italy's official name is as follows:;;;;;;;;), is a unitary parliamentary republic in South-Central Europe. To the north it borders France, Switzerland, Austria and...

, Spain
Spain
Spain , officially the Kingdom of Spain languages]] under the European Charter for Regional or Minority Languages. In each of these, Spain's official name is as follows:;;;;;;), is a country and member state of the European Union located in southwestern Europe on the Iberian Peninsula...

 and Portugal
Portugal
Portugal , officially the Portuguese Republic is a country situated in southwestern Europe on the Iberian Peninsula. Portugal is the westernmost country of Europe, and is bordered by the Atlantic Ocean to the West and South and by Spain to the North and East. The Atlantic archipelagos of the...

, and in Morocco
Morocco
Morocco , officially the Kingdom of Morocco , is a country located in North Africa. It has a population of more than 32 million and an area of 710,850 km², and also primarily administers the disputed region of the Western Sahara...

 and Algeria
Algeria
Algeria , officially the People's Democratic Republic of Algeria , also formally referred to as the Democratic and Popular Republic of Algeria, is a country in the Maghreb region of Northwest Africa with Algiers as its capital.In terms of land area, it is the largest country in Africa and the Arab...

 in north Africa
Africa
Africa is the world's second largest and second most populous continent, after Asia. At about 30.2 million km² including adjacent islands, it covers 6% of the Earth's total surface area and 20.4% of the total land area...

.. In west Asia it has been reported from North forests of Iran. There are records from further east into Asia but these have yet to be confirmed as A. phalloides.

It is ectomycorrhizally associated with a number of tree species, and are symbiotic to them. In Europe, these include a large number of hardwood
Hardwood
Hardwood is wood from angiosperm trees . It may also be used for those trees themselves: these are usually broad-leaved; in temperate and boreal latitudes they are mostly deciduous, but in tropics and subtropics mostly evergreen.Hardwood contrasts with softwood...

 and, less frequently, conifer species. It appears most commonly under oaks but also under beech
Beech
Beech is a genus of ten species of deciduous trees in the family Fagaceae, native to temperate Europe, Asia and North America.-Habit:...

es, chestnut
Chestnut
Chestnut , some species called chinkapin or chinquapin, is a genus of eight or nine species of deciduous trees and shrubs in the beech family Fagaceae, native to temperate regions of the Northern Hemisphere. The name also refers to the edible nuts they produce.-Species:The chestnut belongs to the...

s, horse-chestnuts
Aesculus
The genus Aesculus comprises 13-19 species of woody trees and shrubs native to the temperate northern hemisphere, with 6 species native to North America and 7-13 species native to Eurasia; there are also several hybrids. Species are deciduous or evergreen...

, birch
Birch
Birch is a tree or shrub of the genus Betula , in the family Betulaceae, closely related to the beech/oak family, Fagaceae. The Betula genus contains 30–60 known taxa...

es, filberts, hornbeam
Hornbeam
Hornbeams are relatively small hardwood trees in the genus Carpinus . Though some botanists grouped them with the hazels and hop-hornbeams in a segregate family, Corylaceae, modern botanists place the hornbeams in the birch subfamily Coryloideae...

s, pines, and spruce
Spruce
A spruce is a tree of the genus Picea , a genus of about 35 species of coniferous evergreen trees in the Family Pinaceae, found in the northern temperate and boreal regions of the earth. Spruces are large trees, from tall when mature, and can be distinguished by their whorled branches and conical...

s. In other areas, A. phalloides may also be associated with these trees or only with some species but not others. In coastal California, for example, A. phalloides is associated with coast live oak
Coast Live Oak
Quercus agrifolia, the Coast Live Oak, is an evergreen oak , native to the California Floristic Province. It grows west of the Sierra Nevada from Mendocino County, California, south to northern Baja California in Mexico. It is classified in the red oak section Quercus agrifolia, the Coast Live Oak,...

 but not with the various coastal pine species, such as Monterey pine
Monterey Pine
The Monterey Pine, Pinus radiata, family Pinaceae, also known as the Insignis Pine or Radiata Pine is a species of pine native to the Central Coast of California....

. In countries where it has been introduced it has been restricted to those exotic trees it would associate with in its natural range. There is, however, evidence of A. phalloides associating with hemlock
Tsuga
Tsuga is a genus of conifers in the family Pinaceae. The common name hemlock is derived from a perceived similarity in the smell of its crushed foliage to that of the unrelated plant poison hemlock....

 and with genera of the Myrtaceae
Myrtaceae
The Myrtaceae or Myrtle family are a family of dicotyledon plants, placed within the order Myrtales. Myrtle, clove, guava, feijoa, allspice, and eucalyptus belong here. All species are woody, with essential oils, and flower parts in multiples of four or five...

: Eucalyptus
Eucalyptus
Eucalyptus is a diverse genus of flowering trees in the myrtle family, Myrtaceae. Members of the genus dominate the tree flora of Australia...

in Tanzania and Algeria, and Leptospermum
Leptospermum
Leptospermum is a genus of about 80-86 species of plants in the myrtle family Myrtaceae. Most species are endemic to Australia, with the greatest diversity in the south of the continent; but one species extends to New Zealand, another to Malaysia, and L. recurvum is endemic to Malaysia.They...

and Kunzea
Kunzea
Kunzea is a genus of 36-40 species of shrub in the myrtle family Myrtaceae. They are native to Australia, with one species extending to New Zealand. They are found throughout the Australian continent with most species occurring in southwestern Western Australia...

in New Zealand. This suggests the species may have invasive potential.

By the end of the 19th century, Charles Horton Peck
Charles Horton Peck
Charles Horton Peck, born March 30, 1833 in Sand Lake, New York, died 1917 in Albany, New York, was an American mycologist of the 19th and early 20th centuries...

 had reported A. phalloides in North America. However, in 1918, samples from the Eastern United States were identified as being a distinct though similar species, A. brunnescens
Amanita brunnescens
Amanita brunnescens, also known as the brown American star-footed amanita or cleft-footed amanita is a native North American mushroom of the large genus Amanita. Originally presumed to be Amanita phalloides by renowned American mycologist Charles Horton Peck it was described and named by G. F....

, by G. F. Atkinson of Cornell University
Cornell University
Cornell University is an Ivy League university located in Ithaca, New York, United States. It is a private land-grant university, receiving annual funding from the State of New York for certain educational missions...

. By the 1970s it had become clear that A. phalloides actually does occur in the United States, apparently having been introduced from Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...

 alongside chestnuts, with populations on the West and East Coasts. Although a 2006 historical review concluded that the East Coast populations were introduced, the origins of the West Coast population remained unclear, owing to the scantness of historical records. However, a 2009 genetic study provided strong evidence for the introduced status of the fungus on the west coast of North America.

Amanita phalloides has been conveyed to new countries across the southern hemisphere with the importation of hardwoods and conifers. Introduced oak
Oak
An oak is a tree or shrub in the genus Quercus , of which about 600 species exist. "Oak" may also appear in the names of species in related genera, notably Lithocarpus...

s appear to have been the vector to Australia
Australia
Australia , officially the Commonwealth of Australia, is a country in the Southern Hemisphere comprising the mainland of the Australian continent, the island of Tasmania, and numerous smaller islands in the Indian and Pacific Oceans. It is the world's sixth-largest country by total area...

 and South America
South America
South America is a continent situated in the Western Hemisphere, mostly in the Southern Hemisphere, with a relatively small portion in the Northern Hemisphere. The continent is also considered a subcontinent of the Americas. It is bordered on the west by the Pacific Ocean and on the north and east...

; populations under oaks have been recorded from Melbourne
Melbourne
Melbourne is the capital and most populous city in the state of Victoria, and the second most populous city in Australia. The Melbourne City Centre is the hub of the greater metropolitan area and the Census statistical division—of which "Melbourne" is the common name. As of June 2009, the greater...

 and Canberra
Canberra
Canberra is the capital city of Australia. With a population of over 345,000, it is Australia's largest inland city and the eighth-largest city overall. The city is located at the northern end of the Australian Capital Territory , south-west of Sydney, and north-east of Melbourne...

, as well as Uruguay
Uruguay
Uruguay ,officially the Oriental Republic of Uruguay,sometimes the Eastern Republic of Uruguay; ) is a country in the southeastern part of South America. It is home to some 3.5 million people, of whom 1.8 million live in the capital Montevideo and its metropolitan area...

. It has been recorded under other introduced trees in Argentina
Argentina
Argentina , officially the Argentine Republic , is the second largest country in South America by land area, after Brazil. It is constituted as a federation of 23 provinces and an autonomous city, Buenos Aires...

 and Chile
Chile
Chile ,officially the Republic of Chile , is a country in South America occupying a long, narrow coastal strip between the Andes mountains to the east and the Pacific Ocean to the west. It borders Peru to the north, Bolivia to the northeast, Argentina to the east, and the Drake Passage in the far...

.
Pine
Pine
Pines are trees in the genus Pinus ,in the family Pinaceae. They make up the monotypic subfamily Pinoideae. There are about 115 species of pine, although different authorities accept between 105 and 125 species.-Etymology:...

 plantations are associated with the fungus in Tanzania
Tanzania
The United Republic of Tanzania is a country in East Africa bordered by Kenya and Uganda to the north, Rwanda, Burundi, and the Democratic Republic of the Congo to the west, and Zambia, Malawi, and Mozambique to the south. The country's eastern borders lie on the Indian Ocean.Tanzania is a state...

 and South Africa
South Africa
The Republic of South Africa is a country in southern Africa. Located at the southern tip of Africa, it is divided into nine provinces, with of coastline on the Atlantic and Indian oceans...

, where it is also found under oaks and poplar
Poplar
Populus is a genus of 25–35 species of deciduous flowering plants in the family Salicaceae, native to most of the Northern Hemisphere. English names variously applied to different species include poplar , aspen, and cottonwood....

s.

Toxicity

As the common name suggests, the fungus is highly toxic, and it is responsible for the majority of fatal mushroom poisoning
Mushroom poisoning
Mushroom poisoning refers to harmful effects from ingestion of toxic substances present in a mushroom. These symptoms can vary from slight gastrointestinal discomfort to death. The toxins present are secondary metabolites produced in specific biochemical pathways in the fungal cells...

s worldwide. Its biochemistry has been researched intensively for decades, and it is estimated that 30 grams (1 oz), or half a cap, of this mushroom is enough to kill a human. In 2006, a family of three in Poland
Poland
Poland , officially the Republic of Poland , is a country in Central Europe bordered by Germany to the west; the Czech Republic and Slovakia to the south; Ukraine, Belarus and Lithuania to the east; and the Baltic Sea and Kaliningrad Oblast, a Russian exclave, to the north...

 was poisoned, resulting in one death and the two survivors requiring liver transplants. Some authorities strongly advise against putting suspected death caps in the same basket with fungi collected for the table and to avoid touching them. Furthermore, the toxicity is not reduced by cooking
Thermostability
Thermostability is the quality of a substance to resist irreversible change in its chemical or physical structure at a high relative temperature.Thermostable materials may be used industrially as fire retardants...

, freezing, or drying.

Similarity to edible species

Recent cases highlight the issue of the similarity of A. phalloides to the edible
Edible mushroom
Edible mushrooms are the fleshy and edible fruiting bodies of several species of fungi. Mushrooms belong to the macrofungi, because their fruiting structures are large enough to be seen with the naked eye. They can appear either below ground or above ground where they may be picked by hand...

 paddy straw mushroom, Volvariella volvacea
Volvariella volvacea
Volvariella volvacea is a species of edible mushroom cultivated throughout East and Southeast Asia and used extensively in Asian cuisines. In Chinese, they are called cǎogū Volvariella volvacea (also known as straw mushroom or paddy straw mushroom; syn. Volvaria volvacea, Agaricus volvaceus,...

, with east- and southeast-Asian immigrants in Australia and the west coast of the United States falling victim. In an episode in Oregon
Oregon
Oregon is a state in the Pacific Northwest region of the United States. It is located on the Pacific coast, with Washington to the north, California to the south, Nevada on the southeast and Idaho to the east. The Columbia and Snake rivers delineate much of Oregon's northern and eastern...

, four members of a Korea
Korea
Korea ) is an East Asian geographic region that is currently divided into two separate sovereign states — North Korea and South Korea. Located on the Korean Peninsula, Korea is bordered by the People's Republic of China to the northwest, Russia to the northeast, and is separated from Japan to the...

n family required liver transplants. Of the seven people poisoned in the Canberra
Canberra
Canberra is the capital city of Australia. With a population of over 345,000, it is Australia's largest inland city and the eighth-largest city overall. The city is located at the northern end of the Australian Capital Territory , south-west of Sydney, and north-east of Melbourne...

 region between 1988 and 1998, three were from Laos
Laos
Laos Lao: ສາທາລະນະລັດ ປະຊາທິປະໄຕ ປະຊາຊົນລາວ Sathalanalat Paxathipatai Paxaxon Lao, officially the Lao People's Democratic Republic, is a landlocked country in Southeast Asia, bordered by Burma and China to the northwest, Vietnam to the east, Cambodia to the south and Thailand to the west...

. This misidentification is a leading cause of mushroom poisoning in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...

.

Novices may mistake juvenile death caps for edible puffball
Puffball
A puffball is a member of any of several groups of fungus in the division Basidiomycota. The puffballs were previously treated as a taxonomic group called the Gasteromycetes or Gasteromycetidae, but they are now known to be a polyphyletic assemblage. The distinguishing feature of all puffballs is...

s or mature specimens for other edible Amanita species such as Amanita lanei
Amanita lanei
Amanita lanei , also known as coccora or coccoli, is a white-spored mushroom that fruits naturally in the coastal forests of the western United States during the fall and winter...

, and for this reason some authorities recommend avoiding the collecting of Amanita species for the table altogether. The white form of A. phalloides may be mistaken for edible species of Agaricus
Agaricus
Agaricus is a large and important genus of mushrooms containing both edible and poisonous species, with possibly over 300 members worldwide...

, especially the young fruitbodies whose unexpanded caps conceal the telltale white gills; all mature species of Agaricus have dark-colored gills.

In Europe, other similarly green-capped species collected by mushroom hunters include various green-hued brittlegills of the genus Russula
Russula
Around 750 worldwide species of mycorrhizal mushrooms compose the genus Russula. They are typically common, fairly large, and brightly colored - making them one of the most recognizable genera among mycologists and mushroom collectors...

and the formerly popular Tricholoma flavovirens, now regarded as hazardous owing to a series of restaurant poisonings in France
France
The French Republic , The French Republic , The French Republic , (commonly known as France , is a unitary semi-presidential republic in Western Europe with several overseas territories and islands located on other continents and in the Indian, Pacific, and Atlantic oceans. Metropolitan France...

. Brittlegills, such as Russula heterophylla
Russula heterophylla
The edible wild mushroom Russula heterophylla, that has lately been given the common name of the greasy green brittlegill is placed in the Russula genus, the members of which are mostly known as brittlegills. It is a variably colored mushroom, found in deciduous forests, and woods in Britain,...

, R. aeruginea
Russula aeruginea
Russula aeruginea otherwise knows as the Grass-green Russula, is an inedible russula mushroom, found only under birch, mostly in pine forests; not rare.-Description:...

, and R. virescens
Russula virescens
Russula virescens is a basidiomycete mushroom of the genus Russula, and is commonly known as the green-cracking Russula, the quilted green Russula, or the green brittlegill. It can be recognized by its distinctive pale green cap covered with darker green patches, its crowded white gills, and its...

, can be distinguished by their brittle flesh and the lack of both volva and ring. Other similar species include A. subjunquillea
Amanita subjunquillea
Amanita subjunquillea, also known as the East Asian death cap is a mushroom of the large genus Amanita, which occurs in East and Southeast Asia. Deadly poisonous, it is a member of section phalloideae and related to the death cap A. phalloides.Initially little reported, the toxicity of A...

in eastern Asia
Asia
Asia is the world's largest and most populous continent, located primarily in the eastern and northern hemispheres. It covers 8.7% of the Earth's total surface area and with approximately 3.879 billion people, it hosts 60% of the world's current human population...

 and A. arocheae
Amanita arocheae
Amanita arocheae, also known as the Latin American death cap is a mushroom of the large genus Amanita, which occurs in Central and South America. Deadly poisonous, it is a member of section phalloideae and related to the death cap A. phalloides. It is named after mycologist R. M. Aroche.It is...

, which ranges from Andean Colombia
Colombia
Colombia, officially the Republic of Colombia , is a unitary constitutional republic comprising thirty-two departments. The country is located in northwestern South America, bordered to the east by Venezuela and Brazil; to the south by Ecuador and Peru; to the north by the Caribbean Sea; to the...

 north at least as far as central Mexico
Mexico
The United Mexican States , commonly known as Mexico , is a federal constitutional republic in North America. It is bordered on the north by the United States; on the south and west by the Pacific Ocean; on the southeast by Guatemala, Belize, and the Caribbean Sea; and on the east by the Gulf of...

, both of which are also poisonous.

Biochemistry

The species is now known to contain two main groups of toxins, both multicyclic
Cyclic compound
In chemistry, a cyclic compound is a compound in which a series of atoms is connected to form a loop or ring.While the vast majority of cyclic compounds are organic, a few inorganic substances form cyclic compounds as well, including sulfur, silanes, phosphanes, phosphoric acid, and triboric acid. ...

 (ring-shaped) peptide
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...

s, spread throughout the mushroom tissue
Thallus (tissue)
Thallus, from Latinized Greek θαλλός , meaning a green shoot or twig, is the undifferentiated vegetative tissue of some organisms in diverse groups such as algae, fungus, some liverworts, lichens, and the Myxogastria. Many of these organisms were previously known as the thallophytes, a polyphyletic...

: the amatoxin
Amatoxin
Amatoxins are a subgroup of at least eight toxic compounds found in several genera of poisonous mushrooms, most notably Amanita phalloides and several other members of the genus Amanita, as well as some Conocybe, Galerina and Lepiota mushroom species.-Structure:The compounds have a similar...

s and the phallotoxin
Phallotoxin
The phallotoxins consist of at least seven compounds, all of which are bicyclic heptapeptides , isolated from the death cap . Phalloidin had been isolated in 1937 by Feodor Lynen, Heinrich Wieland's student and son-in-law, and Ulrich Wieland of the University of Munich...

s. Another toxin is phallolysin
Phallolysin
Phallolysin is a toxic hemolysin that has been isolated from the death cap mushroom Amanita phalloides. Phallolysin is a mixture of either two or three proteins of similar structure, each with a molecular weight of 34 kDa. It has shown some hemolytic activity in vitro....

, which has shown some hemolytic (red blood cell–destroying) activity in vitro. An unrelated compound, antamanide
Antamanide
Antamanide is a cyclic decapeptide isolated from a fungus, the death cap: Amanita phalloides. It is being studied as a potential anti-toxin against the effects of phalloidin and for its potential for treating edema....

, has also been isolated.

Amatoxins consist of at least eight compounds with a similar structure, that of eight amino-acid rings; they were isolated in 1941 by Heinrich O. Wieland
Heinrich Otto Wieland
Heinrich Otto Wieland was a German chemist. He won the 1927 Nobel Prize in Chemistry for his research into the bile acids. In 1901 Wieland received his doctorate at the University of Munich while studying under Johannes Thiele...

 and Rudolf Hallermayer of the University of Munich
Ludwig Maximilians University of Munich
The Ludwig Maximilian University of Munich , commonly known as the University of Munich or LMU, is a university in Munich, Germany...

. Of the amatoxins, α-amanitin is the chief component and along with β-amanitin is likely responsible for the toxic effects. Their major toxic mechanism is the inhibition of RNA polymerase II
RNA polymerase II
RNA polymerase II is an enzyme found in eukaryotic cells. It catalyzes the transcription of DNA to synthesize precursors of mRNA and most snRNA and microRNA. A 550 kDa complex of 12 subunits, RNAP II is the most studied type of RNA polymerase...

, a vital enzyme in the synthesis of messenger RNA
Messenger RNA
Messenger RNA is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino acids: a protein...

 (mRNA), microRNA, and small nuclear RNA (snRNA). Without mRNA essential protein synthesis
Protein biosynthesis
Protein biosynthesis is the process in which cells build or manufacture proteins. The term is sometimes used to refer only to protein translation but more often it refers to a multi-step process, beginning with amino acid synthesis and transcription of nuclear DNA into messenger RNA, which is then...

 and hence cell metabolism grind to a halt and the cell dies. The liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

 is the principal organ affected, as it is the organ which is first encountered after absorption in the gastrointestinal tract, though other organs, especially the kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...

s, are susceptible. The RNA polymerase of Amanita phalloides is insensitive to the effects of amatoxins; as such, the mushroom does not poison itself.

The phallotoxins consist of at least seven compounds, all of which have seven similar peptide rings. Phalloidin
Phalloidin
Phalloidin is one of a group of toxins from the death cap known as phallotoxins.-Background:Pioneering work on this toxin was done by the Nobel laureate Heinrich Wieland in the 1930s...

 was isolated in 1937 by Feodor Lynen
Feodor Felix Konrad Lynen
Feodor Felix Konrad Lynen was a German biochemist.- Biography :Feodor Lynen was born in Munich, Germany on 6 April 1911. He started his studies at the chemistry department of Munich University in 1930 and graduated in March 1937 under Heinrich Wieland with the work: "On the Toxic Substances in...

, Heinrich Wieland's student and son-in-law, and Ulrich Wieland of the University of Munich. Though phallotoxins are highly toxic to liver cells, they have since been found to have little input into the death cap's toxicity as they are not absorbed through the gut. Furthermore, phalloidin is also found in the edible (and sought-after) Blusher (Amanita rubescens). Another group of minor active peptides are the virotoxins, which consist of six similar monocyclic heptapeptides. Like the phallotoxins they do not exert any acute toxicity after ingestion in humans.

Symptoms

Death caps have been reported to taste pleasant. This, coupled with the delay in the appearance of symptoms—during which time internal organs are being severely, sometimes irreparably, damaged—makes it particularly dangerous. Initially, symptoms are gastrointestinal in nature and include colicky
Biliary colic
Biliary colic is pain associated with irritation of the viscera secondary to cholecystitis and gallstones. Unlike renal colic, the phrase 'biliary colic' refers to the actual cholelithiasis....

 abdominal pain, with watery diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...

 and vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...

 which may lead to dehydration
Dehydration
In physiology and medicine, dehydration is defined as the excessive loss of body fluid. It is literally the removal of water from an object; however, in physiological terms, it entails a deficiency of fluid within an organism...

, and, in severe cases, hypotension
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...

, tachycardia
Tachycardia
Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...

, hypoglycemia
Hypoglycemia
Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...

, and acid-base disturbances. These first symptoms resolve two to three days after the ingestion. A more serious deterioration signifying liver involvement may then occur—jaundice
Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...

, diarrhea, delirium
Delirium
Delirium or acute confusional state is a common and severe neuropsychiatric syndrome with core features of acute onset and fluctuating course, attentional deficits and generalized severe disorganization of behavior...

, seizures, and coma
Coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...

 due to fulminant hepatic failure and attendant hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy is the occurrence of confusion, altered level of consciousness and coma as a result of liver failure. In the advanced stages it is called hepatic coma or coma hepaticum...

 caused by the accumulation of normally liver-removed substance in the blood. Renal failure
Renal failure
Renal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...

 (either secondary to severe hepatitis
Hepatitis
Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...

 or caused by direct toxic renal damage) and coagulopathy
Coagulopathy
Coagulopathy is a condition in which the blood’s ability to clot is impaired. This condition can cause prolonged or excessive bleeding, which may occur spontaneously or following an injury or medical and dental procedures.The normal clotting process depends on the interplay of various proteins in...

 may appear during this stage. Life-threatening complications include increased intracranial pressure
Intracranial pressure
Intracranial pressure is the pressure inside the skull and thus in the brain tissue and cerebrospinal fluid . The body has various mechanisms by which it keeps the ICP stable, with CSF pressures varying by about 1 mmHg in normal adults through shifts in production and absorption of CSF...

, intracranial hemorrhage, pancreatitis
Pancreatitis
Pancreatitis is inflammation of the pancreas. It occurs when pancreatic enzymes that digest food are activated in the pancreas instead of the small intestine. It may be acute – beginning suddenly and lasting a few days, or chronic – occurring over many years...

, acute renal failure
Acute renal failure
Acute kidney injury , previously called acute renal failure , is a rapid loss of kidney function. Its causes are numerous and include low blood volume from any cause, exposure to substances harmful to the kidney, and obstruction of the urinary tract...

, and cardiac arrest
Cardiac arrest
Cardiac arrest, is the cessation of normal circulation of the blood due to failure of the heart to contract effectively...

. Death generally occurs six to sixteen days after the poisoning.

Up to the mid-20th century, the mortality rate was around 60–70%, but this has greatly reduced with advances in medical care. A review of death cap poisoning throughout Europe from 1971 to 1980 found the overall mortality rate to be 22.4% (51.3% in children under ten and 16.5% in those older than ten). This has fallen further in more recent surveys to around 10–15%.

Treatment

Consumption of the death cap is a medical emergency
Medical emergency
A medical emergency is an injury or illness that is acute and poses an immediate risk to a person's life or long term health. These emergencies may require assistance from another person, who should ideally be suitably qualified to do so, although some of these emergencies can be dealt with by the...

 requiring hospitalization. There are four main categories of therapy for poisoning: preliminary medical care, supportive measures, specific treatments, and liver transplantation
Liver transplantation
Liver transplantation or hepatic transplantation is the replacement of a diseased liver with a healthy liver allograft. The most commonly used technique is orthotopic transplantation, in which the native liver is removed and replaced by the donor organ in the same anatomic location as the original...

.

Preliminary care consists of gastric decontamination with either activated carbon
Activated carbon
Activated carbon, also called activated charcoal, activated coal or carbo activatus, is a form of carbon that has been processed to make it extremely porous and thus to have a very large surface area available for adsorption or chemical reactions.The word activated in the name is sometimes replaced...

 or gastric lavage
Gastric lavage
Gastric lavage, also commonly called stomach pumping or Gastric irrigation, is the process of cleaning out the contents of the stomach. It has been used for over 200 years as a means of eliminating poisons from the stomach. Such devices are normally used on a person who has ingested a poison or...

. However, due to the delay between ingestion and the first symptoms of poisoning, it is commonplace for patients to arrive for treatment many hours after ingestion, potentially reducing the efficacy of these interventions. Supportive measures are directed towards treating the dehydration which results from fluid loss during the gastrointestinal phase of intoxication and correction of metabolic acidosis
Metabolic acidosis
In medicine, metabolic acidosis is a condition that occurs when the body produces too much acid or when the kidneys are not removing enough acid from the body. If unchecked, metabolic acidosis leads to acidemia, i.e., blood pH is low due to increased production of hydrogen by the body or the...

, hypoglycemia, electrolyte
Electrolyte
In chemistry, an electrolyte is any substance containing free ions that make the substance electrically conductive. The most typical electrolyte is an ionic solution, but molten electrolytes and solid electrolytes are also possible....

 imbalances, and impaired coagulation.

No definitive antidote is available, but some specific treatments have been shown to improve survivability. High-dose continuous intravenous penicillin G
Benzylpenicillin
Benzylpenicillin, commonly known as penicillin G, is the gold standard type of penicillin. 'G' in the name 'Penicillin G' refers to 'Gold Standard'. Penicillin G is typically given by a parenteral route of administration because it is unstable in the hydrochloric acid of the stomach...

 has been reported to be of benefit, though the exact mechanism is unknown, and trials with cephalosporin
Cephalosporin
The cephalosporins are a class of β-lactam antibiotics originally derived from Acremonium, which was previously known as "Cephalosporium".Together with cephamycins they constitute a subgroup of β-lactam antibiotics called cephems.-Medical use:...

s show promise. There is some evidence that intravenous silibinin
Silibinin
Silibinin , also known as silybin, is the major active constituent of silymarin, standardized extract of the milk thistle seeds, containing mixture of flavonolignans consisting of among others of silibinin, isosilibinin, silicristin and silidianin. Silibinin itself is mixture of two diastereomers...

, an extract from the blessed milk thistle (Silybum marianum), may be beneficial in reducing the effects of death cap poisoning. A long-term clinical trial of intravenous silibinin has just begun in the US. Silibinin prevents the uptake of amatoxins by hepatocyte
Hepatocyte
A hepatocyte is a cell of the main tissue of the liver. Hepatocytes make up 70-80% of the liver's cytoplasmic mass.These cells are involved in:* Protein synthesis* Protein storage* Transformation of carbohydrates...

s, thereby protecting undamaged hepatic tissue; it also stimulates DNA-dependent RNA polymerases, leading to an increase in RNA synthesis. SLCO1B3
SLCO1B3
Solute carrier organic anion transporter family member 1B3 also known as organic anion-transporting polypeptide 1B3 is a protein that in humans is encoded by the SLCO1B3 gene....

 has been identified as the human hepatic uptake transporter for amatoxins; moreover, substrates and inhibitors of that protein—among others rifampicin
Rifampicin
Rifampicin or rifampin is a bactericidal antibiotic drug of the rifamycin group. It is a semisynthetic compound derived from Amycolatopsis rifamycinica ...

, penicillin, silibilin, antamanide
Antamanide
Antamanide is a cyclic decapeptide isolated from a fungus, the death cap: Amanita phalloides. It is being studied as a potential anti-toxin against the effects of phalloidin and for its potential for treating edema....

, paclitaxel
Paclitaxel
Paclitaxel is a mitotic inhibitor used in cancer chemotherapy. It was discovered in a U.S. National Cancer Institute program at the Research Triangle Institute in 1967 when Monroe E. Wall and Mansukh C. Wani isolated it from the bark of the Pacific yew tree, Taxus brevifolia and named it taxol...

, ciclosporin
Ciclosporin
Ciclosporin , cyclosporine , cyclosporin , or cyclosporin A is an immunosuppressant drug widely used in post-allogeneic organ transplant to reduce the activity of the immune system, and therefore the risk of organ rejection...

 and prednisolone
Prednisolone
Prednisolone is the active metabolite of prednisone, which is also used as a drug.-Uses:Prednisolone is a corticosteroid drug with predominant glucocorticoid and low mineralocorticoid activity, making it useful for the treatment of a wide range of inflammatory and auto-immune conditions such as...

—may be useful for the treatment of human amatoxin poisoning.

N-acetylcysteine has shown promise in combination with other therapies. Animal studies indicate the amatoxins deplete hepatic glutathione
Glutathione
Glutathione is a tripeptide that contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side-chain...

; N-acetylcysteine serves as a glutathione precursor and may therefore prevent reduced glutathione levels and subsequent liver damage. None of the antidotes used have undergone prospective, randomized clinical trials, and only anecdotal support is available. Silibinin and N-acetylcysteine appear to be the therapies with the most potential benefit. Repeated doses of activated carbon may be helpful by absorbing any toxins that are returned to the gastrointestinal tract following enterohepatic circulation
Enterohepatic circulation
Enterohepatic circulation refers to the circulation of biliary acids from the liver, where they are produced and secreted in the bile, to the small intestine, where it aids in digestion of fats and other substances, back to the liver....

. Other methods of enhancing the elimination of the toxins have been trialed; techniques such as hemodialysis
Hemodialysis
In medicine, hemodialysis is a method for removing waste products such as creatinine and urea, as well as free water from the blood when the kidneys are in renal failure. Hemodialysis is one of three renal replacement therapies .Hemodialysis can be an outpatient or inpatient therapy...

, hemoperfusion
Hemoperfusion
Hemoperfusion is a medical process used to remove toxic substances from a patient's blood. The technique involves passing large volumes of blood over an adsorbent substance. The adsorbent substance most commonly used in hemoperfusion are resins and activated carbon...

, plasmapheresis
Plasmapheresis
Plasmapheresis is the removal, treatment, and return of blood plasma from blood circulation. It is thus an extracorporeal therapy...

, and peritoneal dialysis
Peritoneal dialysis
Peritoneal dialysis is a treatment for patients with severe chronic kidney disease. The process uses the patient's peritoneum in the abdomen as a membrane across which fluids and dissolved substances are exchanged from the blood...

 have occasionally yielded success but overall do not appear to improve outcome.

In patients developing liver failure, a liver transplant is often the only option to prevent death. Liver transplants have become a well-established option in amatoxin poisoning. This is a complicated issue, however, as transplants themselves may have significant complications
Complication (medicine)
Complication, in medicine, is an unfavorable evolution of a disease, a health condition or a medical treatment. The disease can become worse in its severity or show a higher number of signs, symptoms or new pathological changes, become widespread throughout the body or affect other organ systems. A...

 and mortality; patients require long-term immunosuppression
Immunosuppression
Immunosuppression involves an act that reduces the activation or efficacy of the immune system. Some portions of the immune system itself have immuno-suppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other...

 to maintain the transplant. That being the case, there has been a reassessment of criteria such as onset of symptoms, prothrombin time
Prothrombin time
The prothrombin time and its derived measures of prothrombin ratio and international normalized ratio are measures of the extrinsic pathway of coagulation. This test is also called "ProTime INR" and "INR PT". They are used to determine the clotting tendency of blood, in the measure of warfarin...

 (PTT), serum bilirubin
Bilirubin
Bilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases...

, and presence of encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy is the occurrence of confusion, altered level of consciousness and coma as a result of liver failure. In the advanced stages it is called hepatic coma or coma hepaticum...

 for determining at what point a transplant becomes necessary for survival. Evidence suggests that, although survival rates have improved with modern medical treatment, in patients with moderate to severe poisoning up to half of those who did recover suffered permanent liver damage. However, a follow-up study has shown that most survivors recover completely without any sequelae if treated within 36 hours of mushroom ingestion.

Notable victims

Several historical figures may have died from Amanita phalloides poisoning (or other similar, toxic Amanitas). These were either accidental poisonings or assassination
Assassination
To carry out an assassination is "to murder by a sudden and/or secret attack, often for political reasons." Alternatively, assassination may be defined as "the act of deliberately killing someone, especially a public figure, usually for hire or for political reasons."An assassination may be...

 plots. Alleged victims of this kind of poisoning include Roman Emperor Claudius
Claudius
Claudius , was Roman Emperor from 41 to 54. A member of the Julio-Claudian dynasty, he was the son of Drusus and Antonia Minor. He was born at Lugdunum in Gaul and was the first Roman Emperor to be born outside Italy...

, Pope Clement VII
Pope Clement VII
Clement VII , born Giulio di Giuliano de' Medici, was a cardinal from 1513 to 1523 and was Pope from 1523 to 1534.-Early life:...

, Tsaritsa Natalia Naryshkina
Natalia Naryshkina
Natalya Kirillovna Naryshkina was the Tsaritsa of Russia from 1671 to 1676 as the second spouse of tsar Alexei I of Russia.-Biography:Coming from a petty noble family, daughter of Kirill Poluektovich Naryshkin and wife Anna Leontyevna Leontyeva Natalya Kirillovna Naryshkina was the Tsaritsa of...

, and Holy Roman Emperor Charles VI.

R. Gordon Wasson recounted the details of these deaths, noting the likelihood of Amanita poisoning. In the case of Clement VII, the illness that led to his death lasted some five months, making the case clearly inconsistent with amatoxin poisoning. Natalia Naryshkina is said to have consumed a large quantity of pickled mushrooms prior to her death. However, it is unclear whether the mushrooms themselves were poisonous or whether she succumbed to food poisoning.

Charles VI experienced indigestion after eating a dish of sautéed
Sautéing
Sautéing is a method of cooking food, that uses a small amount of fat in a shallow pan over relatively high heat. Ingredients are usually cut into pieces or thinly sliced to facilitate fast cooking. The primary mode of heat transfer during sautéing is conduction between the pan and the food being...

 mushrooms. This led to an illness from which he died ten days later — symptomatology consistent with amatoxin poisoning. Charles' death led to the War of Austrian Succession. Noted Voltaire
Voltaire
François-Marie Arouet , better known by the pen name Voltaire , was a French Enlightenment writer, historian and philosopher famous for his wit and for his advocacy of civil liberties, including freedom of religion, free trade and separation of church and state...

, "this dish of mushrooms changed the destiny of Europe."

The case of Claudius' poisoning is more complex. It is known that Claudius was very fond of eating Caesar's mushroom
Amanita caesarea
Amanita caesarea, commonly known in English as Caesar's Mushroom, is a highly regarded edible mushroom in the genus Amanita, native to southern Europe and North Africa. It has a distinctive orange cap, yellow gills and stem. Similar orange-capped species occur in North America and India...

. Following his death, many sources have attributed it to his being fed a meal of death caps instead of Caesar's mushrooms. However, ancient authors such as Tacitus
Tacitus
Publius Cornelius Tacitus was a senator and a historian of the Roman Empire. The surviving portions of his two major works—the Annals and the Histories—examine the reigns of the Roman Emperors Tiberius, Claudius, Nero and those who reigned in the Year of the Four Emperors...

 and Suetonius
Suetonius
Gaius Suetonius Tranquillus, commonly known as Suetonius , was a Roman historian belonging to the equestrian order in the early Imperial era....

 are unanimous about there having been poison added to the mushroom dish, rather than the dish having been prepared from poisonous mushrooms. Wasson speculates that the poison used to kill Claudius was derived from death caps, with a fatal dose of colocynth
Colocynth
Citrullus colocynthis, commonly known as the colocynth, bitter apple, bitter cucumber, egusi, or vine of Sodom , is a viny plant native to the Mediterranean Basin and Asia, especially Turkey , Nubia, and Trieste...

 being administered later during his illness.

See also


External links

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