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Lecture 15 Mushrooms Toxidrome Li

MUSHROOM POISONING: SYNDROMES: • Pediatric exposures EARLY- GI IRRTANT • Numerous • At risk patients: ONSET NEUROTOXIC • o Foragers (inexperienced, foodies, immigrants) (<4 hrs) • Ibotenic acid/muscimol o Experimenters • Psilocybin DISULFIRAM-LIKE • C. atramentarious LIMITATIONS OF IDENTIFICATION: RHABDOMYOLYSIS • R. subnigricans * • Correct identification (genus or species level) is difficult IMMUNOHEMOLYTIC • Paxillus involutus • The edibility (toxicity) may not be known SYNDROME ** o > 10,000 described species worldwide LATE-ONSET HEPATOTOXIC • Cyclopeptide (6-24 hrs) ▪ Toxicity confirmed for ca. 100 species GI  SEIZURES • Gyromitrin ▪ Edibility claimed for ca 2,000 species (monomethylhydrazine) ▪ Individual variation in response to some mushrooms NEPHROTOXIC • A. smithiana et al. ▪ Variation in content depends on geography, DELAYED- RHABDOMYOLYSIS** • T. equestre ONSET conditions, etc NEPHROTOXIC • Cortinarius spp. * (> 24 hrs) o Approx. 1900 described species in SW BC ERYTHROMELALGIA** • Clitocybe spp. NEUROTOXIC** • Hapalopilus rutilans MUSHROOM BIOLOGY: * rare or unconfirmed cases in N. America ** cases not reported in N. • Mushrooms are the above-ground fruiting body (spore-producing America reproductive structure) of fungi EARLY ONSET: • Only appear where and when conditions are right (not always annual) GI IRRITANTS:

o More than one species can grow in a given location INFO • Numerous species, various possible mechanisms

o Territory may change • 2nd most common form of mushroom poisoning reported in • Species may have specific preferred habitats US (after psilocybin) o Disturbed soil, compost, duff, dead trees • Typical onset of symptoms = mins – 4 hours o Some have specific mycorrhizal associations (symbiotic o Usually self-limiting relationships with the root systems of certain trees/plants) TXT • Maintain fluid & electrolyte balance • Avoid antidiarrheal & antisposmadic drugs MUSHROOM IDENTIFICATION: HX • Time of ingestion • Seasonal appearance • Amount ingested • Habitat (what kind of substrate, tree associations, etc) • How many types of mushrooms eaten • Physical characteristics • If anyone else has eaten and symptomatic • • Identification guides and keys Mushrooms consumed at > 1 consecutive meal • Co-ingestants o Visual identification guides for common, distinct species NOTES • If symptom onset > 4 hours post-ingestion, every effort o Dichotomous ID keys (if this, then that) for more complete/ should be made to identify mushrooms detailed/ complicated identification work o Further monitoring including labs may be warranted • A. smithiana can sometimes cause GI sx < 4 hours MUSHROOM PHYSICAL CHARACTERISTICS: NEUROTOXIC: MUSCARINE INFO • Clitocybe spp. , Inocybe spp. MOA • Binds to muscarinic receptors  peripheral cholinergic effects S/S • Vomiting & diarrhea w/in 2 hrs of ingestion • Followed by perspiration, hypersalivation, miosis, shivering and bradycardia • Mostly self-limiting, but fatalities reported TXT • Atropine for moderate to severe symptoms IBOTENIC INFO • muscaria ACID/ • A. pantherina/pantherinoides • Others • Spore print (for spore color) MOA • resembles glutamic acid  o Most toxic mushrooms (, Lepiotas) = white spores! glutaminergic stimulation • Smell, taste, bruising/staining, peelability • Decarboxylated to muscimol  inhibitory • Fleshy characteristics (brittle, flexible, fibrous, etc) S/S • GI upset, dizziness, ataxia, CNS excitation • Followed by CNS depression, seizures, myoclonus jerking SYNDROME CLASSIFICATION: • Death is rare (status epilepticus, aspiration) • Clinical manifestations TXT • Mainly symptomatic and supportive • Time to onset of initial symptoms DISULFIRAM-LIKE: CAVEATS: INFO • Coprinopsis atramentarius (inky cap) and some other • Time to onset of symptoms has a range Coprinus species BUT NOT C. comatus (shaggy mane) • Syndromic classification can be confounded by: MOA • Metabolites of AA coprine inhibit aldehyde dehydrogenase o Ingestion of more than one type of mushroom • Edible, but if alcohol is consumed  acetaldehyde o Staggered ingestions (eaten ≥ 2 consecutive meals) accumulation and “disulfiram-like reaction” o Co-ingestants o Alcohol before mushrooms  delayed (30-120 min) o Contamination (pesticides, microbes, heavy metals) o Alcohol after mushrooms  rapid reaction • Reaction may occur for 3-5 days after mushroom ingestion

Lecture 15 Mushrooms Toxidrome Li LATE ONSET: POISONOUS MUSHROOM FALLACIES:

GYROMITRIN: • Poisonous mushrooms do not turn silver objects black • Poisonous mushrooms do not turn onions, garlics, or rice a particular color INFO • Gyromitra spp. (G. esculenta, G. infula) • Sometimes mistaken for morels • Poisonous mushrooms do not taste bad • European spp up to 10x gyromitrin of N. American spp • Just because insects, slugs, and other animals eat it doesn’t mean a • Poisoning uncommon west of Rockies mushroom is safe to eat MOA • MMH causes hepatotoxicity • Also inhibits pyridoxine-dependent production of GABA POISONOUS MUSHROOM TRUTH: every mushroom is edible … once! SX INGESTION • NVD, cramping, HA, weakness, vertigo, (5-12 h) delirium, seizures (rare), hepatotoxicity SAFE MUSHROOM CONSUMPTION: • Hemolysis in 1-3 days with renal injury • Join a club VAPOURS • Eye and m/m irritation • Learn from knowledgeable members • Systemic toxicity with faster onset (2-8 h) • Get to know the local edibles TXT • Mainly symptomatic and supportive • Eat in moderation • Pyridoxine 25 mg/kg IV recommended for seizures, in addition to benzos SUMMARY:

• Mushroom identification is difficult in many cases NEPHROTOXICITY: o Toxicity can vary within a genus (ex// Amanita spp.) INFO • Amanita smithiana – often confused for pine mushroom • Unintentional exploratory ingestion by kids is generally benign MOA • Toxin(s) responsible not known o Rule out SX • Onset of GI sx (N/V) generally ≥ 5 hours, but has been • reported as early as 20 minutes (raw) Toxidromes, time to onset, and careful history taking can be used to classify • Followed by renal dysfunction over ensuing 1-7 days mushroom poisoning • Moderately elevated ALT & LDH may be seen early on o Beware ingestions of multiple species, repeated/staggered intake TXT • Mainly symptomatic/supportive care & dialysis (9-180 d) • Most patients just need good symptomatic/supportive care • Role of NAC for mild hepatotoxicity not established • Specific txts for some mushrooms – but these are not required often • All known pts so far have recovered renal function! USEFUL WEB RESOURCES: CYCLOPEPTIDE: • Vancouver Mycological Society (www.vanmyco.com) INFO • Amanita phalloides (death cap) • South Van Island Mycological Society (www.svims.ca) o Deadliest mushroom of all o Identification keys, links o Found most often in Vancouver & Victoria in • N. American Mycological Association (www.namyco.org) urban settings, also in Fraser Valley & Gulf Islands • E-flora BC (http://ibis.geog.ubc.ca/biodiversity/eflora/) o Grows in association with hornbeam (Carpinus), • MushroomExpert.com beech, chestnut, hazelnut and oak • MyokWeb.com (California mushrooms, but used for PNW as well) • Conocybe spp. , Galerina spp., Lepiota spp o Galerina spp. least toxic MOA • α-amanitin  inhibits RNA polymerase, stops protein synthesis • amatoxins taken up by liver via OATP, undergoes enterohepatic cycling and renal elimination • Phalloidin  poorly absorbed but causes GI toxicity S/S PHASE 1 • Initial GI toxicity 6-24 h post-ingestion (cramping, abd. pain, vomiting, watery diarrhea, dehydration) PHASE 2 • Apparent recovery but asymptomatic liver damage occurring with rapid rise in transaminases (peak 3-4 days) • Coagulopathy PHASE 3 • By 72 hours GI sx recur • hepatic tenderness, jaundice, hypoglycemia, encephalopathy, renal failure, pancreatic insufficiency • death may occur within 7 days TXT • GI decontamination if recent ingestion • elimination o Aggressively maintain euvolemia o Interrupt enterohepatic cycling (multiple dose charcoal, NPO, octreotide, biliary drainage) • Block uptake of amanitins into liver cells o Silibinin (IV extract from milk thistle), high-dose penicillin, other OATP inhibitors (cyclosporins) • Protect RNA polymerase from attack by amanitins o High dose penicillin, polymyxin B (animal data) • NAC = no proven benefit, but may decrease progression of hepatic encephalopathy, nephropathy & coagulopathy