Amanita phalloides, colloquially known as the “death cap,” belongs to the Phalloideae
section of the Amanita family of mushrooms and is responsible for most deaths following
ingestion of foraged mushrooms worldwide (
1
). On November 28, 2016, members of the Bay Area Mycological Society notified personnel
at the California Poison Control System (CPCS) of an unusually large A. phalloides
bloom in the greater San Francisco Bay Area, coincident with the abundant rainfall
and recent warm weather. Five days later, CPCS received notification of the first
human A. phalloides poisoning of the season. Over the following 2 weeks, CPCS was
notified of an additional 13 cases of hepatotoxicity resulting from A. phalloides
ingestion. In the past few years before this outbreak, CPCS received reports of only
a few mushroom poisoning cases per year. A summary of 14 reported cases is presented
here. Data extracted from patient medical charts revealed a pattern of delayed gastrointestinal
manifestations of intoxication leading to dehydration and hepatotoxicity. Three patients
received liver transplants and all but one recovered completely. The morbidity and
potential lethality associated with A. phalloides ingestion are serious public health
concerns and warrant medical provider education and dissemination of information cautioning
against consuming foraged wild mushrooms.
Initial case. A man aged 37 years (patient A) picked two wild mushrooms in Santa Rosa,
California (Table). He cooked and ate one mushroom, and approximately 10 hours later
developed nausea, vomiting, and diarrhea. He was evaluated in a local emergency department
(ED) for abdominal discomfort 20.5 hours after ingestion. A mycologist identified
the uncooked mushroom sample provided by the patient as A. phalloides. Initial laboratory
findings were notable for an elevated white blood cell count with lactate elevation
and elevated creatinine suggesting dehydration (Table). Liver function tests (LFTs)
6 hours later showed elevated aspartate aminotransferase (AST) (92 IU/L; normal = 15–41)
and alanine aminotransferase (ALT) (95 IU/L; normal = 17–63) levels. He was treated
with aggressive intravenous (IV) fluid hydration, IV octreotide,* and IV silibinin.
†
Two days after ingestion, the patient’s LFTs peaked at AST = 6,159 IU/L, ALT = 3,084
IU/L, total bilirubin = 2.9 mg/dL (normal = 0.2–1.2), and international normalized
ratio (INR) (standardized prothrombin time) 3.2 units (normal = 0.8–1.2). Gastrointestinal
symptoms and laboratory values gradually improved, and the patient was discharged
home on day 6.
TABLE
Demographic and clinical data for 14 patients reported to the California Poison Control
System after Amanita phalloides ingestion — Northern California, December 2016
Patient
Age (yr.)
Sex
Mushrooms ingested
Ingestion to symptom onset (hrs)
Ingestion to hospital admission (hrs)
Initial lactate (mmol/L)*
Initial BUN/Cr† (mg/dL)
Initial AST/ALT§ (U/L)
Peak AST/ALT, INR (units)¶
Hospitalization duration (days)
Outcome
A
37
M
1 (stalk and cap)
10
20
5.2
27/1.4
31/40
3084/6159, 3.2
6
Recovered
B**
26
F
4 caps
9
20
5.87
21/0.64
51/45
11427/9693, 3.2
6
Recovered
C**
28
M
3 caps
9
23
2.98
20/1.46
444/454
6123/4401, 1.4
6
Recovered
D**
1.5 (18 mo.)
F
½ cap
9
19
9.22
16/<0.38
70/47
14300/10200, 10.2
36
Liver transplant, permanent neurologic impairment
E**,††
38
F
1 (stalk and cap)
9
48
7.0
24/0.8
1712/1025
9573/6239, 13.3
13
Liver transplant, recovered
F**
49
F
“Pieces”
9
48
6.72
95/2.24
1038/1100
11940/11350, 4.5
6
Recovered
G
36
M
½ cap
7
12
1.5
18/0.6
32/29
1858/3526, 1.6
5
Recovered
H
56
M
Multiple 8–10 cm caps
12
64
5.4
62/2.33
1599/3200
2820/5599, >13.3
16
Liver transplant, recovered
I
86
F
Unknown
Unknown
~48
Not drawn
64/1.11
768/1084
768/1084, 1.7
3
Recovered
J
93
F
Unknown
Unknown
~48
1.4
64/2.74
765/672
1497/1994, 1.8
9
Recovered
K
19
M
4 caps
12
29
Not drawn
18/0.92
89/151
113/184, 1.2
5
Recovered
L
19
M
8 caps
9
21
1.7
23/1.95
27/29
1404/2544, 2.1
5
Recovered
M††
22
M
2 “shots” of mushroom juice and 3 (stalk and cap)
<12
64
3.2
24/1.31
887/1326
2044/3351, 5.2
9
Recovered
N
22
M
1 “shot” of mushroom juice
4
64
1.7
18/0.94
6344/6400
6344/6400, 2.5
6
Recovered
Abbreviations: ALT = alanine transaminase; AST = aspartate transaminase; BUN = blood
urea nitrogen; Cr = creatinine; F = female; INR = international normalized ratio;
M = male.
* Normal lactate = 0.5–2.2 mmol/L.
† Normal BUN = 7–20 mg/dL; normal Cr = 0.8–1.2 mg/dL.
§ Normal AST = 15–41 U/L; normal ALT = 17–63 U/L.
¶ Normal INR = 0.8–1.2 units.
** Part of a single household cluster of five patients.
†† Discharged from initial hospital with diagnosis of gastroenteritis.
Household cluster. A woman aged 26 years (patient B) prepared and grilled wild mushrooms
for dinner for her husband (patient C, 28 years), her daughter (patient D, 18 months),
her sister (patient E, 38 years), and a female friend (patient F, 49 years). The mushrooms
had been given to her by a person she did not know, who reportedly picked them earlier
in the day in the mountains. The mother, father, and child ate four, three, and one-half
mushroom caps, respectively; the mother’s sister ate one cap and stalk, and the friend
ate “pieces.”
All persons who consumed the mushrooms developed nausea, vomiting, and diarrhea approximately
9 hours after ingestion. The mother, father and child (patients B, C, and D) visited
the ED 20 hours after ingestion with dehydration and gastrointestinal distress. All
patients had laboratory values consistent with hepatic injury (Table). The patients
were treated with aggressive IV fluid hydration, IV octreotide, and IV silibinin.
Two days after ingestion of the mushrooms, the mother’s LFTs peaked at AST 11,427,
ALT 9,693, total bilirubin 2.4 mg/dL, and INR 3.2 units. The father’s LFTs peaked
on hospital day 1 with AST 6,123 IU/L, ALT 4,401 IU/L, and total bilirubin 2.8 on
hospital day 2. Both parents’ symptoms improved, and they were discharged on hospital
days 6 and 4, respectively. The child developed irreversible fulminant hepatic failure
and required mechanical ventilation because of hepatic encephalopathy. She underwent
a liver transplant 6 days after ingestion of the mushroom with a complicated postoperative
course that included cerebral edema and permanent neurologic impairment.
The sister of the woman who prepared the meal (patient E) visited the ED before her
other family members, but was discharged home after administration of IV fluids and
antiemetic medications, with a diagnosis of gastroenteritis. She returned to the ED
the following day with persistent nausea, vomiting, diarrhea, and abdominal cramping.
At that time, her AST was 1,712 IU/L, ALT 1,025 IU/L, total bilirubin 2.0 mg/dL, and
INR 1.8 units. She was treated with aggressive IV fluid hydration, IV octreotide,
and IV silibinin, as well as the placement of a biliary drain, but developed irreversible
fulminant hepatic failure and underwent liver transplant on hospital day 4, with subsequent
improvement of her hepatic function.
The family friend (patient F) visited an ED 2 days after ingestion of the mushrooms,
complaining of abdominal pain, nausea, vomiting, and diarrhea. On hospital day 1,
her LFTs peaked at AST 11,940, ALT 11,350, and INR 4.5. She was treated with aggressive
IV fluid hydration, IV octreotide, and IV silibinin. Her hepatic function recovered,
and she was discharged home on hospital day 6.
Additional cases. In the subsequent 2 weeks, CPCS was notified of eight additional
cases of acute liver injury after consumption of wild mushrooms in northern California
counties (Table). One case involved a man aged 36 years who had ingested mushrooms,
later confirmed to be A. phalloides, obtained from a friend who picked them during
a hike. Another case occurred in a man aged 56 years who was evaluated at an ED 2
days after ingestion of foraged mushrooms and required a liver transplant; two cases
occurred in women aged 86 and 93 years who received wild-picked mushrooms from a friend;
and four men aged 19–22 years who developed hepatotoxicity after ingesting what they
thought were psychedelic mushrooms picked from the wild. Most of these patients had
recovery of hepatic function.
Discussion
Over the course of 2 weeks in December 2016, CPCS investigated 14 suspected A. phalloides
ingestions in five northern California counties. Eleven patients recovered, although
three required liver transplants because of irreversible fulminant hepatic failure.
One of those patients, a child, developed cerebral edema and suffered permanent neurologic
sequelae.
Amatoxins, consisting of alpha, beta, and gamma amanitin, account for >90% of deaths
related to mushroom poisoning worldwide (
1
). A. phalloides contains the alpha variety of amanitin, a cyclic octapeptide thought
to be the primary agent of toxicity in humans (
2
). The amanitins are heat stable and are not inactivated by cooking. Once ingested,
amatoxin is readily absorbed from the gastrointestinal tract into the portal circulation
where it is taken up by hepatocytes, binding to DNA-dependent RNA polymerase (II)
and halting intracellular protein synthesis, ultimately resulting in cell death (
3
). A lethal dose can be as low as 0.1 mg/kg, and a single mushroom can contain up
to 15 mg (
1
). The clinical course of amatoxin poisoning is described in three phases: delayed
gastroenteritis with significant body fluid volume loss (after a postingestion latency
of 6–24 hours), symptomatic recovery (24–36 hours after ingestion), and fulminant
hepatic and multiorgan failure (typically 3–5 days after the ingestion) (
4
). Patients who are evaluated early in the course of their illness might be discharged
home only to return later with indications of liver failure, contributing to the relatively
high case fatality rate (10%–20%) (
5
,
6
). Initial treatment emphasizes early supportive care including aggressive fluid and
electrolyte replacement. In the event of irreversible fulminant liver failure, liver
transplant might be required. A variety of therapies including multidose activated
charcoal, high-dose penicillin, N-acetylcysteine, cimetidine, biliary drainage, and
octreotide have been attempted with no definitive evidence of efficacy. Uncontrolled
observational studies of Amanita intoxication suggest that the early use of silibinin,
a milk thistle derivative, is associated with a reduction in mortality when compared
with historical controls (
7
); however, as with the other aforementioned therapies, evidence supporting efficacy
is lacking because of difficulties associated with conducting randomized controlled
trials. Intravenous silibinin is licensed in Europe, and a clinical trial to evaluate
its efficacy in treatment of hepatic failure induced by Amanita mushroom poisoning
is currently underway in the United States.
§
The majority of silibinin-treated patients in this report received the drug as participants
of this trial.
¶
Medical providers should contact the regional poison control center or a medical toxicology
consultant to assist in the management of any patient with suspected amatoxic mushroom
ingestion.
In California, A. phalloides species grow in a symbiotic relationship with coast live
oak and other hardwood trees (
8
). They can be especially abundant in the early wet winter months, though the foggy
coastal climate and warmer temperatures can support mushroom growth throughout the
year (
4
). In 2016, local mycologists noted an abundance of wild mushroom growth, and California
county health departments reported an increase in the incidence of mushroom poisoning
(
9
). Although weather conditions and increased numbers of A. phalloides poisonings do
not prove a cause and effect relationship, early seasonal rainfall and warmer subsequent
temperatures made a substantial contribution to mushroom proliferation. In addition,
a general increase in naïve foraging and wildcrafting (i.e., gathering plant material
from its native environment for food or medicinal purposes) activities raises risk
for poisoning.
Mycologists recommend exercising caution when foraging or purchasing wild mushrooms
for consumption. If wild mushrooms are to be consumed, specimens should first be examined,
identified, and deemed edible by an experienced mycologist (
4
). Prompt identification of mushroom-related toxic symptoms in the ED and early, aggressive
IV volume replacement are critical first steps in diminishing the significant morbidity
and mortality associated with amatoxin ingestion. Antidotal therapies might also be
considered in conjunction with a consultant experienced in hepatotoxic mushroom poisoning.
In patients with severe poisoning, early contact with the nearest liver transplant
center is recommended. Response to this outbreak included the notification of the
local counties and state department of public health, which subsequently issued a
widely distributed press release (
9
). Measures to disseminate information regarding the dangers of A. phalloides ingestion
are ongoing.
Summary
What is already known about this topic?
Ingestion of Amanita phalloides is responsible for a majority of mushroom-related
deaths worldwide. Amatoxins, the principal toxic alkaloids found in these fungi, cause
cell injury by halting protein synthesis. A possible antidote licensed in most of
Europe, intravenous silibinin, is undergoing evaluation by clinical trial in the United
States.
What is added by this report?
In December 2016, fourteen cases of Amanita phalloides poisoning were identified by
the California Poison Control System (CPCS) among persons who had consumed foraged
wild mushrooms. In the past few years before this outbreak, CPCS only received reports
of a few mushroom poisoning cases per year. All patients in this outbreak had gastrointestinal
manifestations of intoxication leading to dehydration and hepatotoxicity. Three patients
received liver transplants; all patients recovered, although one (a child) had permanent
neurologic impairment.
What are the implications for public health practice?
Wild-picked mushrooms should be evaluated by a trained mycologist before ingestion.
Inexperienced foragers should be strongly discouraged from eating any wild mushrooms.
Health care providers should be aware of the potential for toxicity after wild mushroom
ingestion, that gastrointestinal symptoms mimicking viral gastroenteritis can occur
after ingestion and slowly progress to potentially fatal hepatotoxicity, and should
contact the local poison center for reporting and assistance with management of these
patients.