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Toxicity, Mushroom - Disulfiramlike Toxins

Author: C Crawford Mechem, MD, MS, FACEP, Associate Professor, Department of Emergency Medicine, University of Pennsylvania School of Medicine; Emergency Medical Services Medical Director, Philadelphia Fire Department
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Updated: Jun 1, 2009

Introduction

Background

Edible wild mushrooms often are gathered by foragers and prized for their taste. Occasionally, toxic mushrooms are mistaken for edible species, and human poisoning occurs. In addition, some food aficionados around the globe will intentionally eat certain mushrooms, despite their content of known toxins. For example, Coprinus atramentarius contains the heat-stable toxin, coprine, which only causes toxicity when consumed with ethanol. Because victims of mushroom poisoning will most commonly seek initial medical care in emergency departments, it is important that emergency physicians be familiar with the diverse signs and symptoms of mushroom toxicity.

Coprinus atramentarius

C atramentarius, a member of Coprinaceae or inky cap family, is known familiarly as alcohol inky or inky cap. This mushroom is found particularly during autumn months in urban regions and along roadsides throughout the United States. Its cap is gray-brown, egg-shaped, smooth, and 2-3 inches in width. These mushrooms deliquesce, with gill tissue autodigesting to dark inky liquid after picking and with maturation.

Other coprine-containing mushrooms

Other Coprinus mushrooms that contain coprine include Coprinus insignis, Coprinus quadrifidus, and Coprinus variegatus. Some Coprinus mushrooms generally are not toxic, such as Coprinus comatus (ie, shaggy mane, lawyer's wig), which is sought for its asparagus-like qualities.

Clitocybe clavipes

C clavipes, of the family Tricholomataceae, is also associated with disulfiramlike reactions. However, coprine has not been identified in this species. C clavipes tends to grow in conifer trees or mixed woods and fruits in late autumn or winter. Its cap is gray-brown, mostly flat, and 1-3 inches in width. Gill extends down a stem that is club shaped and thickened near the base. C clavipes is commonly called fat-footed clitocybe or clubfoot funnel cap.

Pathophysiology

C atramentarius contains coprine (N5-1-hydroxycyclopropyl-L-glutamine), a protoxin without intrinsic toxicity. Coprine is metabolized to 1-aminocyclopropanol, which inhibits the enzyme aldehyde dehydrogenase (ALDH). ALDH catalyzes conversion of acetaldehyde to acetic acid.

Inhibition of ALDH produces a clinical syndrome similar to disulfiram (Antabuse) alcohol reaction. Disulfiram has been widely used in the manufacture of rubber since the 1800s. In 1937, an American chemical plant physician noted that employees exposed to disulfiram in the workplace developed a constellation of symptoms after drinking ethanol. These included flushing, headache, nausea, palpitations, and dyspnea, and the symptoms were severe enough to promote abstinence from ethanol. In later years, the basis for this effect, the disulfiram-mediated inhibition of ALDH, was discovered. Ethanol usually is metabolized by alcohol dehydrogenase to acetaldehyde, which is then metabolized by ALDH to acetate and carbon dioxide. Accumulation of acetaldehyde leads to the clinical manifestations of the disulfiram-ethanol interaction.

Disulfiram has been widely used in the treatment of alcohol dependence, although its benefits are the subject of controversy. It has also been used more recently in the management of cocaine dependence.^1,2  

After ingestion of coprine-containing mushrooms, ALDH is inhibited and consumption of ethanol results in acetaldehyde accumulation. This inhibition of ALDH takes at least 30 minutes, which is the time required to metabolize inactive coprine to active 1-aminocyclopropanol. Therefore, small volumes of ethanol ingested concomitantly with mushrooms may not cause toxicity. Enzyme inhibition generally persists for approximately 72 hours but may continue for 5 days. Ingestion of ethanol 3 days after mushroom ingestion may produce acetaldehyde toxicity.

Unlike disulfiram, coprine does not appear to inhibit dopamine beta-hydroxylase, the enzyme that hydroxylates dopamine to form norepinephrine within storage vesicles of presynaptic neurons. In experimental models, rats exposed to coprine are capable of eliciting a tachycardic response to ethanol challenge; those exposed to disulfiram are not capable of eliciting this response (presumably due to inhibition of dopamine beta-hydroxylase). Whether a similar response occurs in humans is unknown.

Frequency

United States

According to the 2007 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS), coprine-containing mushrooms account for a minority of reported mushroom exposures. Of 7733 mushroom exposures reported in 2007, only 16 cases were strongly suspected or confirmed to be related to coprine-containing mushrooms. Seven of these patients were treated in a health care facility. No deaths were reported.³

International

No adequate database exists to determine frequency of coprine exposure or toxicity internationally, although some sources suggest a 1-3% frequency of all reported mushroom poisonings.

Mortality/Morbidity

• With appropriate supportive care, morbidity associated with coprine-induced acetaldehyde toxicity is minimal and recovery is generally complete.
• Mortality and morbidity rates due to secondary effects, such as dehydration or cardiovascular collapse, are unknown. Esophageal rupture attributed to vomiting following co-ingestion of ethanol and coprine-containing mushrooms has been reported, but such cases appear to be infrequent. 

Age

Since ethanol ingestion precedes toxicity, children generally are not affected.

Clinical

History

History of mushroom ingestion is helpful. Raw and cooked mushrooms as well as the cooking water are capable of producing toxicity through ALDH inhibition. Symptoms begin within minutes of ethanol ingestion. Patients may relate symptoms to ethanol, not mushrooms. Ascertaining if other species of wild mushrooms were ingested concomitantly and the approximate elapsed time since ingestion is important. 

• Flushing or blotching red rash (face, neck, thorax)
• Sense of face and hand swelling
• Diaphoresis
• Palpitations/chest pain
• Dyspnea/hyperventilation
• Nausea/vomiting
• Metallic taste
• Headache
• Vertigo/dizziness
• Tingling paresthesias (perhaps due to hyperventilation)
• Apprehension/sense of impending doom
• Weakness

Physical

• Hypertension
• Hypotension
• Tachycardia (occasionally dysrhythmias)
• Flush, particularly of upper half of body (occasionally blotchy red rash of thorax and neck with facial erythema)
• Diaphoresis
• Confusion

Causes

An association with ethanol always exists, although ethanol use may be unintentional (eg, cough syrup).

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