Clinical manifestations

Presentation and course

An exposure history should include the following: (1) quantity and description of mushrooms ingested; (2) preparation of the mushroom (eg, raw or cooked), although cooking may not alter toxicity for many mushroom neurotoxins; (3) source of the mushroom (eg, foraged, online purchase, other); (4) time of ingestion; (5) symptoms seen after ingestion and the time between ingestion and onset; (6) prehospital treatment, including any home remedies (eg, activated charcoal or ipecac); (6) medications regularly taken; and (7) a list of any co-ingestants (including alcohol and cannabis).

At least eight distinct neurologic or myologic presentations of mushroom poisoning have been reported: (1) acute encephalopathy; (2) hallucinations; (3) CNS dysfunction, including cerebellar dysfunction; (4) seizures; (5) cholinergic (muscarinic) syndrome; (6) erythromelalgia; (7) a disulfiram-like reaction; and (8) rhabdomyolysis. There is considerable clinical variation within each of these major categories, depending on age, body weight, toxin concentration within the mushrooms ingested, and the amount ingested. Other factors undoubtedly play a role, including co-ingested substances, medications, genetic susceptibility, and comorbidities (eg, renal or hepatic dysfunction). Clinical features are summarized in Table 3.

Table 3. Neurologic Presentations of Mushroom Poisoning

Prognosis and complications

In 2019, there were no fatalities in these categories of potentially neurotoxic mushroom exposures reported to poison control centers in the United States (13); however, 354 individuals were treated in a healthcare facility, and of these, 112 (32%) suffered a minor adverse outcome, 176 (50%) suffered a moderate adverse outcome, and 8 (2%) suffered a major adverse outcome.

The timing of symptom onset is important for distinguishing life-threatening or severe mushroom poisoning from less serious poisoning. Early symptom onset is generally good with mushroom toxicity because symptom onset in less serious mushroom poisoning generally occurs within 5 to 6 hours of ingestion (eg, with hallucinogenic mushrooms). If symptoms such as vomiting, diarrhea, and abdominal pain begin 5 to 6 hours or more after ingestion, mushrooms that can cause potentially life-threatening or severe toxicity (eg, A. phalloides, Gyromitra spp., or Cortinarius spp.) should be considered (06).

Hallucinogenic mushrooms (“magic mushrooms” or “shrooms”) continue to be fashionable among drug users, especially young drug users, in part because they are often believed to be relatively harmless compared to other hallucinogenic drugs (05). However, serious adverse outcomes have been reported, including myocardial infarction (07); psilocybin-induced takotsubo cardiomyopathy (19); severe rhabdomyolysis, acute renal failure, and posterior encephalopathy (05); psychosis and mania, complicated by violent behavior and rhabdomyolysis (27); and protracted paranoid psychosis (08). Ingestion of magic mushrooms may result in horror trips combined with self-destructive and suicidal behavior, especially among people with mental or psychiatric disorders (23; 14).

Despite the potential for serious adverse outcomes, magic mushroom ingestion is relatively safe (18). Out of 9233 magic mushroom users, 19 (0.2%) reported seeking emergency medical treatment in the past year, with a per-event risk estimate of 0.06%. Young age was the only predictor associated with a higher risk of emergency medical presentations. The most common symptoms were psychological: anxiety/panic and paranoia/suspiciousness. All but one returned to baseline within 24 hours.

Biological basis

Etiology and pathogenesis

Poisoning by toxins of higher fungi of the phylum Basidiomycota is summarized in Table 4. There are at least eight toxidromes and toxin combinations affecting the nervous system or muscle as at least a prominent component.

Table 4. Basidiomycota with Clinically Important Neurotoxins and Myotoxins

Poisoning by toxins of higher fungi of the phylum Ascomycota is summarized in Table 5. There are two known toxidromes affecting the nervous system as at least a prominent component.

Table 5. Ascomycota with Clinically Important Neurotoxins and Myotoxins

Given the structural diversity of chemicals responsible for the multiple forms of mushroom poisoning, it is not surprising that the mechanisms of action vary considerably as well.

Some mushroom toxins produce their associated toxidromes by affecting neurotransmission:

The mushroom-induced disulfiram-like reaction is caused by the fungal toxin coprine (22; 17). Metabolites of coprine inhibit aldehyde dehydrogenase. If alcohol is ingested hours to days after eating coprine-containing mushrooms, the affected individual experiences a constellation of symptoms identical to that from drinking alcohol after taking disulfiram: headache, nausea, vomiting, flushing, tachycardia, and, rarely, hypotension.

For most of the remaining toxidromes, either the responsible toxin is unknown or the mechanism of action of an identified toxin is not understood at a molecular level.

Epidemiology

In a retrospective 11-year review of mushroom poisoning in a Swiss emergency department, the authors identified 87 cases (26). The most common symptoms were nausea and vomiting (82%), followed by diarrhea (68%), syncope (10%), abdominal pain (8%), and hallucinations (7%). Three quarters (74%) exhibited early symptoms (appearance less than 6 hours after ingestion), and one quarter (26%) exhibited late symptoms (appearance more than 6 hours after ingestion). Eleven patients (13%) required hospitalization over 24 hours. Patients with late symptoms tended to have longer in-hospital lengths of stay. Nearly half (44%) were part of cluster presentations (in which more than one person was simultaneously affected).

In the 2019 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (13), there were 5799 reports of single-substance exposures to mushrooms, of which the type of mushroom was unknown or unidentified in 76%. Categories of potentially neurotoxic exposures with substantial numbers of individuals affected were (using their classification system): Group 2 (muscimol or ibotenic acid) 33 cases; Group 3 (monomethylhydrazine) 49 cases; Group 4 (muscarine/histamine) 18 cases; Group 5 (coprine) 10 cases; and Group 6 (psilocybin/psilocin) 590 cases. Thus, most with potentially neurotoxic exposures were for hallucinogenic mushrooms (Groups 2 and 6).

The largest category of identified mushroom exposures reported to poison control centers in the United States was represented by psilocybin or psilocin-containing hallucinogenic mushrooms (13). Of 590 case mentions, there were 387 single exposures, meaning that many of these exposures involved multiple individuals simultaneously. Of the 387 exposures, 144 involved individuals ages 13 to 19 years, 188 involved individuals aged 20 years and older, and 14 involved adults of unknown age. Of these 346 exposures in adolescents and adults, 331 (96%) were acknowledged to have been intentional.

In 2019, no fatalities in these categories of potentially neurotoxic mushroom exposures were reported to poison control centers in the United States (13). However, 354 individuals were treated in a healthcare facility, and of these, 112 (32%) suffered a minor adverse outcome, 176 (50%) suffered a moderate adverse outcome, and 8 (2%) suffered a major adverse outcome.

Exposure to toxic mushrooms is generally accidental in cases of nonhallucinogenic mushroom poisoning (25).

Prevention

Differential diagnosis

Confusing conditions

In the absence of input from people present at the scene, the differential diagnosis will often depend on the dominant symptoms at presentation. When acute gastrointestinal symptoms (nausea, vomiting, abdominal pain, or cramps) predominate in an emergency setting, common considerations include infectious and noninfectious gastroenteritis, food poisoning (eg, Staphylococcal food poisoning), migraine, and iatrogenic causes (eg, NSAIDS, chemotherapy, opiates) as well as, potentially, morning sickness in primiparous women of childbearing age. The history and examination may alternatively suggest a more serious form of gastrointestinal pathology related to a functional disorder (eg, gastroparesis), obstruction (eg, esophageal stricture, pyloric stenosis, small bowel obstruction), or other organic disorders (eg, pancreatitis, peptic ulcer disease, cholecystitis, hepatitis, appendicitis, inflammatory bowel disease).

If ingestion or poisoning is suspected, various toxins need to be considered (depending on the particular presenting symptoms), including alcohol, cannabis, hallucinogens (LSD, PCP, etc.), glue-sniffing, nitrous oxide, anticholinergics, opiates, sympathomimetics (eg, methamphetamine, cocaine), etc. When considering hallucinogenic mushroom toxicity, it is important to keep in mind that (1) recreational exposures are often multiple; (2) mushrooms obtained by foraging are frequently misidentified; and (3) mushrooms obtained illicitly may also be misidentified and may contain adulterants.

Diagnostic workup

The diagnosis of mushroom poisoning should be based on the presenting syndrome and supported, if possible, by the description and toxicologic analysis of the mushroom (09; 10). Unfortunately, according to data from the American Association of Poison Control Centers, the exact mushroom species and toxins in cases of mushroom poisoning go unidentified in at least three quarters of the cases (09; 10; 13). Ideally, a sample of the mushrooms ingested should be obtained so a mycologist can confirm identification. Unfortunately, in most cases, the mushroom in question has already been digested, but collecting the patient’s gastric contents using gastric lavage or after emesis might yield identifiable spores.

No particular diagnostic procedures are available or needed for most patients with hallucinogenic mushroom toxicity, although identification of the mushroom by a mycologist is still desirable. The regional poison control center may be contacted for consultation, referral, and assistance in mushroom identification. In the United States, a nationwide telephone number automatically directs calls to the nearest poison control center (1-800-222-1222). A mycologist can also be contacted through the North American Mycological Association, a local university, or sometimes a botanical garden.

The following blood studies are recommended for most patients evaluated on an emergency basis with possible mushroom toxicity: complete blood count, basic serum metabolic profile, baseline liver and renal function studies, and creatine kinase. Urine drug testing should also be considered, especially if the patient exhibits alterations of behavior or mental status or if substance abuse, suicidal intent, or foul play is suspected.

Management

The management recommendations presented here do not apply to poisoning with nonneurologic toxins, such as those that cause solely gastrointestinal symptoms or those more dangerous hepatotoxic and nephrotoxic varieties that are associated with high case-fatality rates.

Gastrointestinal decontamination. There is a limited and somewhat controversial role for gastrointestinal decontamination in cases of mushroom poisoning, with some advocating use of activated charcoal in the first hour and others discounting this as insufficient evidence of efficacy. Furthermore, the CNS manifestations of hallucinogenic mushroom toxicity, for example, develop rapidly after ingestion, with absorption before activated charcoal is usually considered. A reasonable approach is to consider activated charcoal administration in alert patients who present for care within 1 hour of potentially toxic mushroom ingestion. Patients admitted to the hospital are typically given activated charcoal to stop the toxic compound’s absorption and to prevent further intoxication, even though adsorption to activated charcoal has not been demonstrated for these fungal toxins. Supportive evidence for the efficacy of activated charcoal administration in this setting is largely indirect, from animal studies and from analogy with other toxic ingestions. Because of the potential for further volume depletion, combining a cathartic (eg, sorbitol) and activated charcoal is not generally recommended. Syrup of ipecac administration in remote locations soon after pediatric ingestion of toxic mushrooms may prevent or minimize toxicity, but unsupervised children typically only try exploratory nibbles of mushrooms in their local environments and, thus, rarely have serious consequences. Because most serious mushroom poisonings are only detected hours after ingestion, gastric emptying by gastric lavage or syrup of ipecac in the emergency department is not likely to be beneficial. If treatment occurs within the first hour of ingestion, gastric lavage may be considered, although this recommendation also lacks strong empiric evidence. Nasogastric aspiration in alert patients to obtain a sample for spore analysis can be considered if no other mushroom sample of what was ingested is available and gastric contents might still contain partially digested mushrooms.

Hallucinogenic mushroom toxicity. Care is primarily supportive in hallucinogenic mushroom toxicity, the most frequent form of neurotoxic mushroom poisoning. Most patients can be treated without medications. Toxicity usually lasts between 6 and 8 hours, but some symptoms may take several days to subside. Occasionally, benzodiazepines may be needed for sedation and to help control associated agitation and panic attacks. Intravenous fluids may sometimes be necessary to correct volume loss from vomiting.

Seizures are uncommon with hallucinogenic mushroom poisoning, except in young children. Various anticonvulsants have been used to treat seizures in such patients, but respiratory depression may occur when some of these agents (eg, benzodiazepines) are administered intravenously. Preparations must, therefore, be made to support the airway if necessary.

In rare cases, anticholinergic drugs, such as atropine, may be needed. With A muscaria poisoning, anticholinergic drugs (eg, atropine) are rarely, if ever, needed; the species name was applied because muscarine was first identified from preparations of this mushroom, even though few muscarinic effects are observed following ingestion of these mushrooms.

In the absence of a clinically evident infection, treating a low-grade fever with antipyretics is unnecessary in an agitated or hyperactive patient with hallucinogenic mushroom ingestion.

If symptoms such as vomiting, diarrhea, and abdominal pain begin 5 to 6 hours or more after ingestion, mushrooms that can cause potentially life-threatening or severe toxicity (eg, A. phalloides or Cortinarius spp.) should be considered.

Other neurologic and myotoxic forms of mushroom poisoning. Care is also primarily supportive and symptomatic for most other neurologic and myologic presentations of mushroom poisoning.

Cholinergic (muscarinic) mushroom poisoning should be treated with atropine.

Intensive care may be needed for patients with myotoxic mushroom poisoning and severe rhabdomyolysis.

Pyridoxine should be given after substantial ingestion of gyromitrin-containing (false morel) mushrooms or if central nervous system toxicity is present; repeat doses may be needed. Diazepam should be administered intravenously if seizures persist despite pyridoxine in patients exposed to gyromitrin-containing (false morel) mushrooms.

Outcomes

Except for the myotoxic and false morel neurologic toxidromes, neurologic and myologic presentations of mushroom poisoning are rarely fatal. Fatalities have uncommonly occurred with other neurologic toxidromes (eg, cholinergic mushroom poisoning).

Other serious and often permanent organ dysfunction or fatalities may result from accidentally ingesting a more toxic mushroom resembling one that is hallucinogenic, edible, or conditionally edible. For example, some individuals who intend to harvest or procure “magic mushrooms” (ie, hallucinogenic mushrooms) obtain instead more toxic species, like some species of mushrooms of the genus Cortinarius, which are nephrotoxic (24). A common feature among all species in the genus Cortinarius is that young specimens have a “cortina” (veil) between the cap and the stem, hence the name, meaning curtained. The renal toxicity of these mushrooms can vary, presumably based on toxin dose and physical constitution, from mild, transient renal failure to irreversible total acute renal failure that necessitates continual dialysis (24). The nephrotoxicity of Cortinarius orellanus was first recognized in the 1950s when this mushroom was identified as the cause of a mass poisoning of 135 people in Bydgoszcz, Poland, which resulted in 19 deaths (11). Affected individuals develop an acute tubulointerstitial nephritis (with severe interstitial nephritis, acute focal tubular damage, and interstitial fibrosis). The responsible toxin was identified to be orellanine, a bipyridine N-oxide compound. Renal symptom onset is typically delayed 1 to 2 weeks after ingestion, although patients may have gastrointestinal discomfort in the latency period (11).

Factors that increase the risk of a fatal outcome include age (eg, young children or the elderly) and amount ingested.