Aside from transplantation, few specific therapies have been shown to have clinical benefit. Benzathine penicillin is one of the most commonly used therapeutic options but demonstrates little efficacy.¹¹ The same review showed the most favorable outcomes with silibinin, which is an extract from the milk thistle plant. Unfortunately, dosing is not standardized, and this therapy appears to be difficult to obtain in the United States.

Gyromitrin

Also known as the false morel, appropriately dubbed for its resemblance to the highly prized morel mushroom (Morchella esculenta), Gyromitra sp. mushrooms rarely can cause severe neurologic toxicity and seizures. Gastrointestinal symptoms are usually delayed at least 5-10 hours after ingestion, and most patients recover fully. However, because of metabolism, gyromitrin is converted in vitro to monomethylhydrazine, which interrupts pyridoxal-phosphate related reactions, including those involved in GABA synthesis. As GABA is an inhibitory neurotransmitter, seizures may be precipitated and can be refractory to benzodiazepine therapy. As in isoniazid overdose, which works biochemically in the same fashion, treatment should include repeated boluses of vitamin B6 (recommended dose of 70 mg/kg IV).⁶ Patients with this ingestion should be admitted for neurologic checks.

Orelline/Orellanine

Though more prevalent in Europe, Cortinarius sp. found in the United States also contain the toxic compound orellanine. With a particularly insidious course, delayed toxicity in this mushroom ingestion may not be preventable. The earliest symptoms, such as gastritis, chills, and headache, tend to occur 1 day after ingestion, but oliguric renal failure tends to begin days to weeks after ingestion. It follows a pattern of interstitial nephritis, and there is no benefit to detoxification by hemodialysis early on; but it is the mainstay of treatment once nephrotoxic damage has set in.⁹ Renal transplantation has been warranted in some cases.

Rhabdomyolysis Toxins

While the specific toxin has not yet been elucidated, certain Tricholoma sp. mushrooms have been linked to remarkable cases of rhabdomyolysis with creatine kinase levels greater than 200,000 U/L.6 In a case series involving this ingestion, all individuals had ingested the mushrooms on multiple consecutive days.¹² There were three fatalities, and autopsy revealed myocardial as well as skeletal muscle damage. Onset of symptoms was delayed, beginning 1-3 days after the last meal, and included fatigue, weakness, and myalgias.

Allenic Norleucine

Different Amanita sp. mushrooms in Europe (proxima) and the United States (smithiana) have recently challenged the long-held belief that early gastrointestinal effects following mushroom ingestion belied an overall benign clinical course. In the 1990s, both in Europe and in the Pacific Northwest of the United States, multiple patients with mushroom ingestions characterized by early gastrointestinal symptoms developed accelerated renal failure. Allenic norleucine, among other compounds, has been found to be the culprit, and toxicity is about twice as rapid as orellanine (12 hours vs. 24 hours, respectively). This particular ingestion is not accounted for by many of the earlier syndromic classification schemes, but it is included in recent work by Diaz.^7,8