INTRODUCTION — Amanita smithiana is a mushroom found primarily on the West Coast of North America. Toxic ingestion causes a syndrome of acute gastroenteritis within minutes to hours of consumption followed by delayed onset acute kidney injury within one week. Although uncommon, A. smithiana poisoning has increased in frequency over the last two decades [1]. It represents the only known mushroom poisoning syndrome where ingestion of a single type of mushroom can have immediate acute effects that are followed by serious delayed toxicity (table 1).
This topic will discuss the epidemiology, toxicity, clinical manifestations, and management of A. smithiana mushroom poisoning. Evaluation and management of other poisonous mushrooms are discussed separately.
●(See "Clinical manifestations and evaluation of mushroom poisoning".)
●(See "Management of mushroom poisoning (except amatoxin-containing mushrooms)".)
EPIDEMIOLOGY — A. smithiana is a white mushroom that grows in pine forests on the West coast of North America, primarily from British Columbia to Northern California, though they have been observed as far south as the mountains of New Mexico [2]. Ingestion has also been reported in Southeast Asia [3]. A. smithiana mushrooms grow in the autumn until the time of the first frost, typically growing near dead or rotting wood.
Toxicity from A. smithiana was first described in 1964, although its toxic effects were misattributed to A. phalloides [4]. Following the initial report, almost 30 years passed without a documented case. In the 1990s, A. smithiana mushroom poisoning became more commonly described in association with increasing culinary popularity and economic value of the matsutake or pine mushroom (Tricholoma magnivelare), which has a similar habitat and appearance [2,5-7]. Publication of the book "Matsutake Mushroom: White gold rush of the 1990s" in 1997 coincided with the largest spike in reports of these ingestions in 1997 and 1998 [8]. In all cases of poisoning reported to date, A. smithiana have been ingested by individuals collecting and preparing the look-alike matsutake or pine mushroom (picture 1) for personal culinary use.
Matsutake mushrooms are also extremely desirable for commercial culinary use. Matsutakes have been gathered in regions where A. smithiana is native and sold to restaurants in areas where A. smithiana is not, making poisoning possible outside of the West coast of North America or Southeast Asia [8].
Children are also at risk from unintentional sampling of the A. smithiana mushroom although exploratory mushroom ingestions in children typically consist of one bite and serious poisoning in this setting is rare. (See "Clinical manifestations and evaluation of mushroom poisoning", section on 'Epidemiology'.)
A recent case series suggested that other Amanita species found in Europe (eg, A. boudieri, A. gracilior, and A. echinocephala) may produce toxicity similar to that seen with A. Smithiana [9]. Although these mushrooms were not found to contain allenic norleucine, the purported toxin in A. smithiana, they did have a substance identified by thin layer chromatography that was also found in a toxic extract from A. smithiana.
MUSHROOM APPEARANCE — Mushroom identification is usually not readily available during the acute phase of care, and most mushrooms causing toxicity are never correctly identified. However, if possible, determination of the specific type of mushroom ingested can be helpful for treatment recommendations and prognosis. Consultation with a poison control center is strongly advised when attempting mushroom identification. (See 'Additional resources' below.)
A. smithiana is usually white, though color can vary (brown, gray, or yellow) based upon weather during growth. It has a universal veil on the cap. The cap may range from 5 to 17 cm across. The stipe (or stem) may be from 6 to over 16 cm (picture 1). The stipe does not have the volva (bulbous cup at the base of the stem) seen on many other Amanita species.
PHARMACOTOXICOLOGY AND PATHOPHYSIOLOGY — The toxin in A. smithiana has not been conclusively elucidated, but allenic norleucine is widely felt to be the component most likely to cause the described clinical toxicity [9]. A. smithiana contains the toxin allenic norleucine (amino-hexadienoic acid) which is present in A. smithiana mushrooms and causes kidney toxicity in cell culture and animal models [10-12]. Both raw and cooked A. smithiana appear to cause toxicity, suggesting allenic norleucine is a heat-stable toxin [2,5-7].
Allenic norleucine is not related to amatoxin found in other more commonly ingested and phylogenetically related Amanita mushrooms such as Amanita phalloides, A. virosa, A. verna, or A. bisporigera.
Several observations indicate that allenic norleucine rather than orelline or other toxins cause the kidney toxicity seen in A. smithiana poisoning [11]:
●Allenic norleucine and A. smithiana extract caused identical renal tubular epithelial cell necrosis within 12 hours in a cell culture model.
●Renal tubular epithelial cells incubated with orelline (the toxin from the largest group of delayed kidney toxicity mushrooms) displayed a different pattern of toxicity and slower onset of cell death. (See "Clinical manifestations and evaluation of mushroom poisoning", section on 'Delayed renal failure'.)
●The C-terminus of the allenic norleucine is hypothesized to confer the toxicity of the molecule, as non-allenic norleucine does not cause kidney toxicity.
●When renal tubular epithelial cells are incubated with allenic norleucine and glutathione, there was no change in the observed toxicity, suggesting that N-acetylcysteine is unlikely to affect the clinical course of A. smithiana ingestion.
Human pathologic findings have been described in one patient who underwent kidney biopsy 43 days after suspected A. smithiana mushroom ingestion [4]. Light microscopy showed diffuse interstitial fibrosis without inflammatory changes. Renal tubules were dilated and contained cellular debris. Electron microscopy showed involvement of both the proximal and distal tubules. Many large vesicles were present, and mitochondrial membranes were disrupted.
EVALUATION — In patients with suspected mushroom poisoning, the clinician should provide prompt support of airway, breathing, and circulation, as needed. A regional poison control center should be contacted to discuss likely mushroom species ingested based upon clinical findings, identification of any mushrooms available for analysis, and treatment of specific toxic effects. Most poison control centers maintain active call lists of mycologists who are knowledgeable concerning local prevalence of mushroom genera and species and can assist in mushroom identification. (See 'Additional resources' below.)
The table provides a description of the various mushroom poisoning syndromes (table 1). A discussion of the clinical recognition and management of poisoning by other mushroom species is discussed in detail separately. (See "Clinical manifestations and evaluation of mushroom poisoning" and "Management of mushroom poisoning (except amatoxin-containing mushrooms)" and "Amatoxin-containing mushroom poisoning (eg, Amanita phalloides): Clinical manifestations, diagnosis, and treatment".)
Diagnosis of A. smithiana mushroom poisoning relies upon the recognition of the clinical presentation. The diagnosis is strengthened by specific mushroom identification if available. (See 'Mushroom identification' below.)
Clinical manifestations — A. smithiana mushrooms cause symptoms 20 minutes to 12 hours after ingestion with the typical onset occurring within three hours. Initial clinical findings include [2,5-7]:
●Nausea
●Vomiting
●Abdominal cramping
●Diarrhea (less common)
●Increased urine output (less common)
●Diaphoresis (less common)
●Dizziness (less common)
Nausea and vomiting typically gives way to an asymptomatic period after 6 to 24 hours of symptoms although persistent nausea and vomiting has been described [2,5-7]. There are no reports of major abnormalities of airway, breathing, or circulation during this initial phase of A. smithiana toxicity.
Three to six days after A. smithiana mushroom consumption, patients begin to have symptoms of kidney failure, most notably oliguria and anuria [2,5-7]. A large percentage of patients seek initial medical care during this "delayed" time frame (three to six days), as the initial symptoms are self-limited. Decreased urine output is the primary presenting complaint [2,5-7]. Kidney failure typically ensues and will gradually resolve over several weeks to months with proper supportive care. Other than kidney failure, patients have few clinical effects in other organ systems during the recovery period [2,5-7].
Ancillary studies — There is no clinically available test for allenic norleucine. Specific testing to identify mushrooms and their toxins is discussed separately. (See "Clinical manifestations and evaluation of mushroom poisoning", section on 'Mushroom identification'.)
Acute testing in patients with mushroom exposures is guided by the clinical presentation. Asymptomatic children with ingestions that are unlikely to be toxic may be observed without any testing. Patients with ingestion of potentially toxic mushrooms, including A. smithiana should undergo baseline assessment of the following:
●Serum electrolytes, calcium, and phosphate
●Blood urea nitrogen and serum creatinine
●Urinalysis
●Liver studies (eg, aspartate aminotransferase [AST], alanine aminotransferase [ALT], total protein, albumin, total and direct bilirubin)
●Prothrombin time (PT), partial thromboplastin time (PTT)
●Complete blood count with platelets
If acute kidney injury is present, additional studies to obtain include (see "Diagnostic approach to adult patients with subacute kidney injury in an outpatient setting"):
●Urine sodium concentration
●Urine creatinine concentration
●Renal ultrasound
Acute kidney injury is typically not evident on laboratory evaluation immediately after ingestion of A. smithiana mushrooms. The creatinine begins to rise within 24 hours of ingestion. The kidney injury from A. smithiana will gradually worsen over the course of a week. Kidney function, acid-base status, and serum electrolytes should be monitored over the next several weeks to determine if dialysis is necessary [2,5-7].
In contrast to acute kidney injury from A. smithiana, orellanine-containing mushrooms, such as Cortinarius species, Mycena pura, and Omphalatus orarius, display kidney toxicity in a more delayed fashion with evidence of acute kidney injury typically presenting later (up to 20 days after consumption) although large ingestion may cause symptoms as early as three days after orellanine-containing mushroom consumption. (See "Clinical manifestations and evaluation of mushroom poisoning", section on 'Delayed renal failure'.)
Several cases of A. smithiana mushroom poisoning have demonstrated small initial elevations in AST and ALT up to 300 to 400 units/L (approximately six times the normal upper limit of normal); these appear to resolve by day four postingestion [2,5-7]. Lactate dehydrogenase (LDH) has also been noted to be elevated in several of the described patients. In contrast, after A. phalloides poisoning, hepatic damage will be the primary feature of ingestion, and serum transaminase levels will continue to rise to very high levels.
Mushroom identification — Whenever possible, samples of all ingested mushrooms should be obtained. Whole mushrooms are preferred, but identification can be made on parts of the mushroom, especially the cap. Storage is facilitated by wrapping the mushrooms in wax paper, placing it in a paper bag, and refrigerating the sample. Storage in plastic bags should be avoided. Unfortunately, patients often ingest multiple mushrooms and have cooked or otherwise damaged the fungi they have ingested, making direct identification difficult if not impossible. Many regional poison control centers have access to mycologists who can assist with mushroom identification. (See 'Additional resources' below.)
Successful laboratory confirmation of A. smithiana using thin layer liquid chromatography analysis of specimens from a raw mushroom and mushroom soup has been described [13]. However, specimen transport to a research lab was necessary and this test is not typically available to practicing clinicians.
Techniques for mushroom identification are discussed in greater detail separately. (See "Clinical manifestations and evaluation of mushroom poisoning", section on 'Mushroom identification'.)
DIFFERENTIAL DIAGNOSIS — The differential diagnosis of mushroom poisoning typically relies upon clinical manifestations and recognition of specific mushroom poisoning syndromes (table 1). Patients with A. smithiana mushroom poisoning may have clinical or laboratory findings of hepatotoxicity and kidney disease that overlap with the poisoning syndromes caused by amatoxin-and orellanine-containing mushrooms.
When compared with victims of amatoxin-containing mushroom poisoning, patients with A. smithiana ingestion may have small elevations in liver aminotransferases up to 300 to 400 units/L but will usually not have values over 1000 units/L. The liver aminotransferase elevations associated with A. smithiana poisoning will resolve by four days postingestion. In contrast, patients with amatoxin-containing mushroom poisoning typically have continued elevation beyond four days after mushroom consumption. In circumstances where A. smithiana ingestion cannot be clinically differentiated from amatoxin-containing mushroom poisoning, the clinician should initiate specific therapy for amatoxin-containing mushroom toxicity (See "Amatoxin-containing mushroom poisoning (eg, Amanita phalloides): Clinical manifestations, diagnosis, and treatment", section on 'Management' and "Amatoxin-containing mushroom poisoning (eg, Amanita phalloides): Clinical manifestations, diagnosis, and treatment", section on 'Clinical manifestations'.)
Patients with orellanine-containing mushroom poisoning typically have a more delayed onset of symptoms than victims of A. smithiana poisoning; gastrointestinal symptoms occur up to four days after mushroom consumption and acute kidney injury typically occurs more than one week postingestion. (See "Clinical manifestations and evaluation of mushroom poisoning", section on 'Delayed renal failure'.)
Other mushroom poisoning syndromes are discussed in greater detail separately. (See "Clinical manifestations and evaluation of mushroom poisoning", section on 'Mushroom poisoning syndromes'.)
DIAGNOSIS — A. smithiana mushroom poisoning is a clinical diagnosis in a patient who reports a foraged mushroom meal followed by a gastrointestinal illness that starts within the first three hours, then acute kidney injury that develops three to six days later. The diagnosis is strengthened by mushroom identification, but laboratory confirmation of the mushroom is not readily available to clinicians, and there are no confirmatory tests.
MANAGEMENT — Recommendations for the care of children and adults with A. smithiana mushroom poisoning are derived from case series and reports [2,5-7]. Treatment focuses on the prevention of toxin absorption and supportive care. There is no specific antidote.
Possible amatoxin-containing mushroom — In circumstances where A. smithiana ingestion cannot be clinically differentiated from amatoxin-containing mushroom poisoning, the clinician should initiate specific therapy for amatoxin-containing mushroom toxicity. (See "Amatoxin-containing mushroom poisoning (eg, Amanita phalloides): Clinical manifestations, diagnosis, and treatment", section on 'Management' and "Amatoxin-containing mushroom poisoning (eg, Amanita phalloides): Clinical manifestations, diagnosis, and treatment", section on 'Clinical manifestations'.)
Vomiting and diarrhea — Vomiting may be treated with an antiemetic (eg, ondansetron 0.15 mg/kg intravenously) to facilitate administration of activated charcoal soon after ingestion. Vomiting that is induced more than 60 minutes after toxin ingestion does not significantly reduce absorption. Thus, it is presumed that inhibition of spontaneous vomiting beyond that time frame will not increase toxin absorption and symptomatic treatment of vomiting is also appropriate. (See 'Gastrointestinal decontamination' below.)
Fluid repletion should be given based upon clinical assessment of losses and evidence of dehydration. Patients with signs of shock should receive prompt fluid resuscitation (algorithm 1). However, care should be taken not to overhydrate patients with oliguric or anuric kidney failure. (See "Treatment of severe hypovolemia or hypovolemic shock in adults" and "Initial management of shock in children" and "Maintenance and replacement fluid therapy in adults" and "Treatment of hypovolemia (dehydration) in children".)
Acute kidney injury — Dialysis is frequently, though not always, required in cases of A. smithiana ingestion for replacement of kidney function. The effect of dialysis on toxin elimination has not been evaluated. All cases of A. smithiana-induced kidney failure have been self-limited. Supportive dialysis has typically been necessary for between two to five weeks, though in one case it was required for six months [5-7]. Dialysis typically begins four to seven days after mushroom ingestion and has been performed in the inpatient and outpatient settings [5-7].
The major complications of acute kidney injury include volume overload, hyperkalemia, metabolic acidosis, hypocalcemia, and hyperphosphatemia. The initial assessment therefore includes the careful evaluation of volume status and measurement of serum electrolytes, particularly potassium and bicarbonate, and evaluation of a complete blood count and serum phosphate, calcium, albumin and uric acid. (See "Clinical manifestations and evaluation of mushroom poisoning", section on 'Acute gastroenteritis and delayed renal failure' and "Clinical manifestations and evaluation of mushroom poisoning", section on 'Delayed renal failure'.)
Accepted indications for dialysis in patients with kidney failure generally include (see "Kidney replacement therapy (dialysis) in acute kidney injury in adults: Indications, timing, and dialysis dose"):
●Fluid overload that is refractory to diuretics
●Hyperkalemia (serum potassium concentration >6.5 mEq/L) or rapidly rising serum potassium, as can occur in rhabdomyolysis
●Metabolic acidosis (arterial pH less than 7.10) in patients with volume overload, which will be made worse by the administration of sodium bicarbonate, or with lactic acidosis, which is generally not treated with bicarbonate.
●Signs of uremia, such as pericarditis, neuropathy, or an otherwise unexplained decline in mental status
Gastrointestinal decontamination — We recommend that alert patients who ingest A. smithiana mushrooms and present within one hour of ingestion receive activated charcoal (1 g/kg, maximum dose: 50 g). The recommendation for AC administration soon after A. smithiana mushroom consumption derives from indirect evidence of benefit in volunteers who ingested other toxins, animal studies, and evidence of benefit following ingestions of other mushrooms. Mushrooms, like most complex xenobiotics, bind well to activated charcoal. Because diarrhea is a common occurrence after A. smithiana poisoning, the combination of a cathartic (eg, sorbitol) and AC should be avoided. The greatest benefit occurs if AC is given within one hour of ingestion. Of note, AC is unlikely to be of benefit in most instances of A. smithiana poisoning because patients do not typically seek medical attention until days after mushroom consumption [2,5-7].
The efficacy of AC as a function of time from ingestion is discussed in detail separately. (See "Gastrointestinal decontamination of the poisoned patient", section on 'Evidence of efficacy and adverse effects'.)
We recommend that patients who ingest potentially toxic mushrooms not undergo gastric emptying by gastric lavage or syrup of ipecac in the emergency department. This recommendation is based upon randomized controlled trials showing minimal benefit and possible risk to patients who undergo gastric emptying after poisoning. Syrup of ipecac administered in locations far from definite medical care and soon after pediatric mushroom ingestion may prevent toxicity [14]. (See "Clinical manifestations and evaluation of mushroom poisoning", section on 'Mushroom identification' and "Gastrointestinal decontamination of the poisoned patient", section on 'Syrup of Ipecac'.)
Elimination enhancement — No methods of elimination enhancement, including multiple dose activated charcoal, hemoperfusion, or hemodialysis have been shown to reduce the concentration or effect of allenic norleucine, the primary toxin contained in A. smithiana.
DISPOSITION — Mushroom identification is often not available. Thus, disposition after mushroom poisoning is typically guided by clinical findings. Consultation with a regional or international poison control center is advised to assist with disposition decisions. (See 'Additional resources' below and "Management of mushroom poisoning (except amatoxin-containing mushrooms)", section on 'Disposition'.)
The following patients warrant hospital admission:
●Patients with delayed symptoms more than six hours after mushroom ingestion
●Patients with early symptoms less than three hours after mushroom ingestion who remain symptomatic beyond six hours despite supportive care or who ingested more than one type of mushroom
●Patients with acute kidney injury
●Asymptomatic patients after a known ingestion of A. smithiana in whom outpatient follow-up cannot be assured
Asymptomatic patients after a known ingestion of A. smithiana may be followed as outpatients as long as monitoring of kidney function starting at three days and occurring daily up to seven days can be assured.
ADDITIONAL RESOURCES
Regional poison control centers — Regional poison control centers in the United States are available at all times for consultation on patients with known or suspected poisoning, and who may be critically ill, require admission, or have clinical pictures that are unclear (1-800-222-1222). In addition, some hospitals have medical toxicologists available for bedside consultation. Whenever available, these are invaluable resources to help in the diagnosis and management of ingestions or overdoses. Contact information for poison centers around the world is provided separately. (See "Society guideline links: Regional poison control centers".)
SUMMARY AND RECOMMENDATIONS
●Epidemiology – Amanita smithiana is a large white mushroom (picture 1) that grows in the pine forests of the West Coast of North American and in Southeast Asia. It is typically ingested unintentionally by individuals seeking the edible pine (or matsutake) mushroom (Tricholoma magnivelare) (picture 1). (See 'Epidemiology' above.)
●Clinical manifestations – The clinical presentation of A. smithiana mushroom poisoning consists of self-limited acute gastroenteritis (nausea, vomiting, and diarrhea) starting 20 minutes to 12 hours after consumption, with the typical onset occurring within three hours and vomiting typically giving way to an asymptomatic period after 6 to 24 hours. Acute kidney injury becomes clinically apparent presenting with decreased urine output three to six days after ingestion. (See 'Clinical manifestations' above.)
●Ancillary studies – Patients with ingestion of potentially toxic mushrooms, including A. smithiana, should have serum electrolytes, calcium, phosphate, blood urea nitrogen, creatinine, liver function tests, coagulation profile, and complete blood count. If acute kidney injury is present, obtain urine sodium and creatinine concentrations and renal ultrasound. (See 'Ancillary studies' above.)
●Diagnosis – A. smithiana mushroom poisoning is a clinical diagnosis in a patient who reports a foraged mushroom meal followed by a gastrointestinal illness that starts within the first three hours, then acute kidney injury that develops three to six days later. The diagnosis is strengthened by mushroom identification, but laboratory confirmation of the mushroom is not readily available to clinicians, and there are no confirmatory tests. (See 'Diagnosis' above.)
●Management – Treatment of A. smithiana mushroom poisoning focuses on the prevention of toxin absorption and supportive care. There is no specific antidote. (See 'Management' above.)
•Contact poison control center – When mushroom poisoning is suspected, a regional poison control center should be contacted to discuss likely mushroom species ingested based upon geography, season, and clinical findings; to assist with identification of any mushrooms available for analysis; and to provide treatment recommendations. (See 'Regional poison control centers' above.)
•Possible amatoxin-containing mushroom exposure – In circumstances where A. smithiana ingestion cannot be clinically differentiated from amatoxin-containing mushroom poisoning (ie, presence of liver injury), the clinician should initiate specific therapy for amatoxin-containing mushroom toxicity. (See 'Differential diagnosis' above and 'Possible amatoxin-containing mushroom' above.)
•Gastrointestinal decontamination – In an alert patient who ingest A. smithiana mushrooms and presents within one hour of ingestion, we recommend treatment with activated charcoal (1 g/kg, maximum dose: 50 g) (Grade 1B). (See 'Gastrointestinal decontamination' above.)
In a patient who ingests potentially toxic mushrooms, we recommend they not undergo gastric emptying by gastric lavage or syrup of ipecac in the emergency department (Grade 1B). (See 'Gastrointestinal decontamination' above.)
•Vomiting and diarrhea – Vomiting may be treated with an antiemetic (eg, ondansetron 0.15 mg/kg intravenously). Fluid repletion should be given based upon clinical assessment of losses and evidence of dehydration. However, care should be taken not to overhydrate patients with oliguric or anuric kidney failure. (See 'Vomiting and diarrhea' above.)
•Acute kidney injury – A. smithiana-induced acute kidney injury is self-limited, although dialysis is often required. Recovery to baseline kidney function typically occurs within two to five weeks but may be delayed up to six months. (See 'Acute kidney injury' above.)
●Disposition – The following patients warrant hospital admission (see 'Disposition' above):
•Patients with delayed symptoms more than six hours after mushroom ingestion
•Patients with early symptoms less than three hours after mushroom ingestion who remain symptomatic beyond six hours despite supportive care or who ingested more than one type of mushroom
•Patients with acute kidney injury
•Asymptomatic patients after a known ingestion of A. smithiana in whom outpatient follow-up cannot be ensured
