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MUSHROOM-INDUCED ERYTHROMELALGIA

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Ingestion of Clitocybe amoenolens or Clitocybe acromelalga has resulted in erythromelalgia, a painful peripheral, inflammatory condition. These mushrooms are also known as "Poison Dwarf Bamboo Mushroom". Clitocybe acromelalga may be confused with species Armillaria mellea, Clitocybe gibba, and Lactarius sanguifluus; Clitocybe amoenolens may be confused with species Clitocybe gibba (Common Funnel Cap) or Lepista inversa (Edible Blewit).

Specific Substances

    A) CONSTITUENTS OF THE GROUP
    1) Clitocybe amoenolens - "Poison Dwarf Bamboo mushroom"
    2) Clitocybe acromelalga
    3) Poison Dwarf Bamboo Mushroom - "Clitocybe amoenolens"
    SYNONYMS
    1) Mushrooms-Induced Erythromelalgia

Overview

Laboratory Monitoring

    A) Patients usually recover within 8 days to 5 months, usually without any residual effects. Careful neurologic work-up and follow-up is indicated in patients with neurologic signs or symptoms.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is primarily supportive. There is no known antidote for prevention or treatment of erythromelalgia. Patients usually recover within 8 days to 5 months, usually without any residual effects. Careful neurologic work-up and follow-up are indicated in patients with neurologic signs or symptoms.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) In patients with erythromelalgia, pain is poorly relieved by analgesics; however, dipping the feet and hands into cold water may partially relieve symptoms. Secondary sources have claimed efficacy of nicotinamide and triphosphate adenosine for this condition, but no primary literature supporting their use was found at the time of this review. Patient's will likely require opioid analgesics in order to maintain adequate pain control. Admission for large doses of intravenous analgesics may be necessary.
    C) DECONTAMINATION
    1) PREHOSPITAL: There is no role for prehospital charcoal administration in this ingestion.
    2) HOSPITAL: Patients generally do not present to medical care until symptoms develop and GI decontamination is no longer useful. If a patient present shortly after ingestion consider activated charcoal.
    D) ANTIDOTE
    1) None.
    E) PATIENT DISPOSITION
    1) HOME CRITERIA: Patients in whom symptoms are controlled may be observed at home.
    2) OBSERVATION CRITERIA: Observation is typically not indicated. If the patient has an acute exposure with no symptoms, they may be instructed to return if symptoms develop.
    3) ADMISSION CRITERIA: Patients whose pain cannot be adequately controlled with outpatient pain medications may require inpatient admission for pain control.
    4) CONSULT CRITERIA: Consult a mycologist for identification of the mushroom, often available through your local poison center. Consult a medical toxicologist or poison center for patients with persistent symptoms or in whom the diagnosis is not clear.
    F) TOXICOKINETICS
    1) Onset of symptoms usually occurs 24 hours to several days after mushroom ingestion, followed by 3 to 5 weeks of intolerable pain in the same area. Patients usually recover within 8 days to 5 months, usually without any residual effects. Symptoms may be dose-dependent.
    G) DIFFERENTIAL DIAGNOSIS
    1) Ciguatoxin, heavy metals (particularly mercury), pyrethrin and pyrethroid insecticides, peripheral neuropathy from medical causes such as diabetes, vasculitis.

Range Of Toxicity

    A) TOXICITY: At the time of this review, no fatalities have been reported following the ingestion of Clitocybe amoenolens or Clitocybe acromelalga. Erythromelalgia has been reported after ingestion of these mushrooms but the dose necessary to cause toxicity is unknown.

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) GENERAL INFORMATION: Clitocybe amoenolens grows in Morocco and Europe, and is found in autumn growing in cedar or high alpine forests. Clitocybe acromelalga is found in September through November in bamboo forests mostly in Korea and Japan.
    B) TOXICOLOGY: Ingestion of acromelic acid-containing mushrooms (Clitocybe amoenolens, Clitocybe acromelalga) has results in erythromelalgia, a painful peripheral, inflammatory condition. Patients may experience intense burning pain, redness, and edema of the hands and feet, often intensified by heat and relieved by cold. The histopathologic examination of the patient's skin has revealed perivascular mononuclear infiltration and prominent perivascular dermal edema without vasculitis. NMDA and non-NMDA receptors are present in small unmyelinated sensory nerve endings in the skin; it has been proposed that these peripheral glutamate receptors of skin nerve endings may be the source of pain associated with inflammation.
    C) EPIDEMIOLOGY: Exposures are very rare.
    D) WITH POISONING/EXPOSURE
    1) Erythromelalgia has been reported following the ingestion of Clitocybe amoenolens or Clitocybe acromelalga mushrooms. Patients may experience paresthesia of the extremities (tingling and pinprick sensations), edema of the feet and violent and paroxysmal nocturnal burning pains (electric shock sensations), a local heat sensation and erythema, fatigue, and insomnia. Pain is often intensified by heat and relieved by cold. Onset of symptoms usually occurs 24 hours to several days after mushroom ingestion, followed by 3 to 5 weeks of intolerable pain in the same area. Symptoms may be dose-dependent. Patients usually recover within 8 days to 5 months, usually without any residual effects. Symptoms may also resolve spontaneously within a couple of days of ingestion.
    0.2.20) REPRODUCTIVE
    A) At the time of this review, no data were available to assess the potential effects of exposure to Clitocybe acromelalga and Clitocybe amoenolens mushrooms during pregnancy. It is unknown whether these mushrooms are excreted in human breast milk. One study reported that the toxins are heat-proof and are probably not excreted in breast-milk. A 4-month-old breast-fed infant did not experience any symptoms after her mother ingested clitocybe amoenolens mushrooms in two occasions.

Clinical Effects

Summary Of Exposure

    A) GENERAL INFORMATION: Clitocybe amoenolens grows in Morocco and Europe, and is found in autumn growing in cedar or high alpine forests. Clitocybe acromelalga is found in September through November in bamboo forests mostly in Korea and Japan.
    B) TOXICOLOGY: Ingestion of acromelic acid-containing mushrooms (Clitocybe amoenolens, Clitocybe acromelalga) has results in erythromelalgia, a painful peripheral, inflammatory condition. Patients may experience intense burning pain, redness, and edema of the hands and feet, often intensified by heat and relieved by cold. The histopathologic examination of the patient's skin has revealed perivascular mononuclear infiltration and prominent perivascular dermal edema without vasculitis. NMDA and non-NMDA receptors are present in small unmyelinated sensory nerve endings in the skin; it has been proposed that these peripheral glutamate receptors of skin nerve endings may be the source of pain associated with inflammation.
    C) EPIDEMIOLOGY: Exposures are very rare.
    D) WITH POISONING/EXPOSURE
    1) Erythromelalgia has been reported following the ingestion of Clitocybe amoenolens or Clitocybe acromelalga mushrooms. Patients may experience paresthesia of the extremities (tingling and pinprick sensations), edema of the feet and violent and paroxysmal nocturnal burning pains (electric shock sensations), a local heat sensation and erythema, fatigue, and insomnia. Pain is often intensified by heat and relieved by cold. Onset of symptoms usually occurs 24 hours to several days after mushroom ingestion, followed by 3 to 5 weeks of intolerable pain in the same area. Symptoms may be dose-dependent. Patients usually recover within 8 days to 5 months, usually without any residual effects. Symptoms may also resolve spontaneously within a couple of days of ingestion.

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) ERYTHROMELALGIA
    1) WITH POISONING/EXPOSURE
    a) Two families (5 patients) developed erythromelalgia after ingesting Clitocybe amoenolens mushrooms (Saviuc et al, 2001).
    b) FAMILY ONE: A 40-year-old man developed paresthesia of the extremities (tingling and pinprick sensations) after ingesting Clitocybe amoenolens mushrooms. His symptoms resolved spontaneously within a couple of days of ingestion (Saviuc et al, 2001).
    1) After ingesting Clitocybe amoenolens mushrooms on two different occasions, a 32-year-old woman developed paresthesia of the extremities (tingling and pinprick sensations), edema of the feet and violent and paroxysmal nocturnal burning pains (electric shock sensations), a local heat sensation and erythema, fatigue, insomnia, and paroxysmal pains. Capillaroscopy did not reveal any capillary injury. Although acetaminophen and dextropropoxyphen did not relieve her pain, dipping her feet and hands into cold water partially relieved her symptoms. She was prescribed clonazepam for 3 months and full recovery was observed within several weeks of ingestion (Saviuc et al, 2001)
    2) A 3-year-old boy developed numbness of the feet with a sensation of pricking needles and paroxysmal painful attacks with insomnia after ingesting Clitocybe amoenolens mushrooms on two different occasions, . Physical examination revealed slight edema, erythema and cyanosis during pain paroxysms. Acetaminophen and dipping extremities into cold water partially relieved his symptoms (Saviuc et al, 2001)
    c) FAMILY TWO: A 32-year-old woman developed numbness of the toes for several days after ingesting Clitocybe amoenolens mushrooms (Saviuc et al, 2001).
    1) After ingesting two plates of Clitocybe amoenolens mushrooms, a 35-year-old man developed paresthesia and pains of both feet and hands, sensations of burning and violent paroxysmal pains (mostly at night with crisis occurring every 30 minutes), insomnia, and general weakness. Symptoms became more severe with movement, heat, contact, and pressure, and were partly relieved by dipping the extremities into cold water. Several drugs were not effective: acetaminophen, buprenorphine, carbamazepine, clonazepam, dextropropoxyphen, dihydroergocryptine, methysergide, nicergoline and prazosin. Edematous areas became reddish and warm during crisis. In addition, local sweating and trophic injuries (intertrigo, erosion, crusting) of the toes were noted. Three months postingestion, electromyography revealed mild polyneuropathy with sensorimotor fiber impairment, predominantly of the sural nerves. He was treated with acetylsalicylic acid (aspirin) 2 g/day, clomipramine 75 mg/day intravenously, and morphine chlorhydrate 80 to 120 mg/day. After 11 days, improvement was observed and he was discharged home with the same treatment taken orally. On follow-up six months later, he still complained of intermittent burning painful sensations of the feet. Three years later, he still had polyneuropathy, possibly caused by prolonged cutaneous contact with ice cubes (Saviuc et al, 2001)
    d) CASE SERIES: Three patients developed erythromelalgia after eating Clitocybe acromelalga mushrooms. The first patient, a 73-year-old man developed reddening, swelling, burning/sharp pain, and numbness in the hands and feet 4 hours after ingesting a meal containing Clitocybe acromelalga mushrooms and presented 22 days after the initial onset of symptoms. Despite treatment with aspirin (200 mg/day), his symptoms persisted for about 1 month. He continued to have numbness in the hands and feet as a sequela. The second patient, an 80-year-old woman, developed severe pain, reddening, swelling, burning sensation, and persistent allodynia 4 days after cooking and eating Clitocybe acromelalga mushrooms. Despite treatment with aspirin, pregabalin, mecobalamin, and tocopheryl nicotinate, no improvement was noted. At this time, she received an intermittent high dose of IV nicotinic acid for 1 hour/day (initially 20 mg/day and gradually increased to 100 mg/day for 7 day) followed by oral nicotinic acid amide (initially 100 mg/day and gradually decreased, and discontinued after 3 months). Initially, she developed a very mild crawling sensation of the face, but her symptoms gradually improved over the next 7 days. Her son developed slight reddening of the extremities with light pain/burning sensation. He recovered without any drug therapy (Nakajima et al, 2013).
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) NEUROPATHY
    a) In one animal study, increasing doses of Clitocybe amoenolens mushrooms were given to 4 rats (1- to 25-fold the dose eaten by a severely poisoned patient) to evaluate toxicity of these mushrooms. Loss of body weight, skin lesions, locomotor disability and erythema of the toes were reported in 2 rats receiving the highest doses. Electron microscopic examination of sciatic nerves revealed decreased axon density and neuronal fiber degeneration (Saviuc et al, 2003).

Dermatologic

    3.14.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) SKIN LESIONS
    a) In one animal study, increasing doses of Clitocybe amoenolens mushrooms were given to 4 rats (1- to 25-fold the dose eaten by a severely poisoned patient) to evaluate toxicity of these mushrooms. Loss of body weight, skin lesions, locomotor disability and erythema of the toes were reported in 2 rats receiving the highest doses. It was suggested that skin lesions might be explained by the presence of acromelic acid A, a kainate analogue (Saviuc et al, 2003).

Reproductive

    3.20.1) SUMMARY
    A) At the time of this review, no data were available to assess the potential effects of exposure to Clitocybe acromelalga and Clitocybe amoenolens mushrooms during pregnancy. It is unknown whether these mushrooms are excreted in human breast milk. One study reported that the toxins are heat-proof and are probably not excreted in breast-milk. A 4-month-old breast-fed infant did not experience any symptoms after her mother ingested clitocybe amoenolens mushrooms in two occasions.
    3.20.3) EFFECTS IN PREGNANCY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of exposure to Clitocybe acromelalga and Clitocybe amoenolens mushrooms during pregnancy.
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) It is unknown whether Clitocybe acromelalga and Clitocybe amoenolens are excreted in human breast milk. One study reported that the toxins are heat-proof and are probably not excreted in breast-milk (Saviuc et al, 2001).
    2) CASE REPORT - A 4-month-old breast-fed infant did not experience any symptoms after her mother ingested clitocybe amoenolens mushrooms in two occasions. The mother experienced paresthesia of the limb extremities (tingling and pinprick sensations). She developed edema of the feet and violent and paroxysmal nocturnal burning pains (electric shock sensations) (Saviuc et al, 2001).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Patients usually recover within 8 days to 5 months, usually without any residual effects. Careful neurologic work-up and follow-up is indicated in patients with neurologic signs or symptoms.

Methods

    A) Approximately 2 dozen toxins, such as acromelic acid A-E (the most abundant and powerful kainoid amino acid), have been isolated from Clitocybe acromelalga. Ingestion of acromelic acid-containing mushrooms (Clitocybe amoenolens, Clitocybe acromelalga) has resulted in erythromelalgia, a painful peripheral, inflammatory condition (Diaz, 2005; Saviuc et al, 2001; Bessard et al, 2004; Saviuc et al, 2003; Benjamin, 1995). A specific and sensitive liquid chromatographic-mass spectrometric method has been developed that detects and quantifies acromelic acid A concentration in mushrooms (Bessard et al, 2004).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients whose pain cannot be adequately controlled with outpatient pain medications may require inpatient admission for pain control.
    6.3.1.2) HOME CRITERIA/ORAL
    A) Patients in whom symptoms are controlled may be observed at home.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a mycologist for identification of the mushroom, often available through your local poison center. Consult a medical toxicologist or poison center for patients with persistent symptoms or in whom the diagnosis is not clear.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Observation is typically not indicated. If the patient has an acute exposure with no symptoms, they may be instructed to return if symptoms develop.
    B) Onset of symptoms usually occurs 24 hours to several days after mushroom ingestion, followed by 3 to 5 weeks of intolerable pain in the same area. Patients usually recover within 8 days to 5 months, usually without any residual effects. Symptoms may be dose-dependent. There were no recurrence (follow-up for 3 years) (Saviuc et al, 2001).

Monitoring

    A) Patients usually recover within 8 days to 5 months, usually without any residual effects. Careful neurologic work-up and follow-up is indicated in patients with neurologic signs or symptoms.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) PREHOSPITAL: There is no role for prehospital charcoal administration in this ingestion.
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY: Patients generally do not present to medical care until symptoms develop and GI decontamination is no longer useful. If a patient present shortly after ingestion consider activated charcoal.
    B) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) SUPPORT
    1) MANAGEMENT OF MILD TO MODERATE TOXICITY
    a) Treatment is primarily supportive. There is no known antidote for prevention or treatment of erythromelalgia. Patients usually recover within 8 days to 5 months, usually without any residual effects. Careful neurologic work-up and follow-up are indicated in patients with neurologic signs or symptoms.
    2) MANAGEMENT OF SEVERE TOXICITY
    a) In patients with erythromelalgia, pain is poorly relieved by analgesics; however, dipping the feet and hands into cold water may partially relieve symptoms. Secondary sources have claimed efficacy of nicotinamide and triphosphate adenosine for this condition, but no primary literature supporting their use was found at the time of this review. Patient's will likely require opioid analgesics in order to maintain adequate pain control. Admission for large doses of intravenous analgesics may be necessary.
    3) Save all emesis and stools in refrigerator (DO NOT FREEZE) for possible microscopic study and analysis.
    4) HISTORY OF CURRENT ILLNESS
    a) The following questions should be asked in taking the medical history regarding the exposure of the patient to the mushroom:
    1) At what time were the mushrooms eaten?
    2) When was the onset of symptoms after the ingestion?
    3) Was the mushroom eaten at more than one meal?
    4) Were the mushrooms eaten again later and, if so, were they reheated?
    5) Was the mushroom eaten raw or cooked?
    6) Was any alcohol consumed within 24 hours of the meal?
    7) Was more than one kind of mushroom ingested?
    8) How were the mushrooms stored between collection and preparation?
    9) What was the condition of the mushrooms at the time of preparation?
    10) How were the mushrooms prepared (ie, raw, sauteed, fried, soup, stew)?
    11) Are ALL persons who ate the mushroom ill?
    12) Are persons in the group who ate NONE of the mushroom ill?
    13) Other important questions regarding the mushroom include:
    a) What kind of substrate was it growing on (eg, wood, soil)?
    b) What kind of tree(s) was it growing near?
    c) What time of year was the mushroom collected?
    B) MONITORING OF PATIENT
    1) Patients usually recover within 8 days to 5 months, usually without any residual effects. Careful neurologic work-up and follow-up are indicated in patients with neurologic signs or symptoms.
    C) ERYTHROMELALGIA
    1) In patients with erythromelalgia, pain is poorly relieved by analgesics; however, dipping the feet and hands into cold water partially relieved symptoms. Secondary sources have claimed efficacy of nicotinamide and triphosphate adenosine for this condition, (Saviuc et al, 2001) but no primary literature supporting there use was found at the time of this review.
    2) In one patient with erythromelalgia, acetaminophen and dextropropoxyphene did not relieve the pain; however, dipping the feet and hands into cold water partially relieved symptoms. In another patient acetaminophen and dipping extremities into cold water partially relieved the pain (Saviuc et al, 2001).
    3) One patient with severe symptoms did not experience any relief following the use of acetaminophen, buprenorphine, carbamazepine, clonazepam, dextropropoxyphene, dihydroergocryptine, methysergide, nicergoline and prazosin. He subsequently was treated with acetylsalicylic acid (aspirin) 2 g/day, clomipramine 75 mg/day intravenously, and morphine chlorohydrate 80 to 120 mg/day. After 11 days, improvement was observed and he was discharged home with the same treatment taken orally. (Saviuc et al, 2001).
    4) NICOTINIC ACID: An 80-year-old woman developed severe pain, reddening, swelling, burning sensation, and persistent allodynia 4 days after cooking and eating Clitocybe acromelalga mushrooms. Despite treatment with aspirin, pregabalin, mecobalamin, and tocopheryl nicotinate, no improvement was noted. At this time, she received an intermittent high dose of IV nicotinic acid for 1 hour/day (initially 20 mg/day and gradually increased to 100 mg/day for 7 day) followed by oral nicotinic acid amide (initially 100 mg/day and gradually decreased, and discontinued after 3 months). Initially, she developed a very mild crawling sensation of the face, but her symptoms gradually improved over the next 7 days. Her son developed slight reddening of the extremities with light pain/burning sensation. He recovered without any drug therapy (Nakajima et al, 2013).

Enhanced Elimination

    A) LACK OF INFORMATION
    1) There is no information regarding the effectiveness of hemodialysis or hemoperfusion for the removal of Clitocybe amoenolens and Clitocybe acromelalga from plasma.

Range Of Toxicity

Summary

    A) TOXICITY: At the time of this review, no fatalities have been reported following the ingestion of Clitocybe amoenolens or Clitocybe acromelalga. Erythromelalgia has been reported after ingestion of these mushrooms but the dose necessary to cause toxicity is unknown.

Minimum Lethal Exposure

    A) At the time of this review, no fatalities have been reported following Clitocybe amoenolens or Clitocybe acromelalga ingestions(Saviuc et al, 2001).

Maximum Tolerated Exposure

    A) Erythromelalgia has been reported following the ingestion of Clitocybe amoenolens or Clitocybe acromelalga (Saviuc et al, 2001).

Pharmacology Toxicology

Toxicologic Mechanism

    A) Approximately 2 dozen toxins, such as acromelic acid A-E, have been isolated from Clitocybe acromelalga. Acromelic acid is structurally similar to domoic and kainic acid; they are members of the kainoic family, a group of non-proteinogenic pyrrolidine dicarboxylic acids. Domoic acid is the compound that is found in some shellfish and is responsible for producing a devastating neurological disorder. Acromelic acid A has glutamate agonist activity. In animal studies, it was shown that acromelic acid A has neuroexcitatory activity, can bind glutamate receptors, mimics glutamic acid, causes characteristic behavior changes and induces selective damages to the interneurons of the lower spinal chord. (Bessard et al, 2004; Saviuc et al, 2003; Saviuc et al, 2001; Benjamin, 1995).
    B) Glutamate receptors (eg; N-methyl-D-aspartate (NMDA), amino-5-methyl-4-isoxazole-propionic acid (AMPA), and kainate subtypes) are mainly expressed in the central nervous system (Saviuc et al, 2001). Ingestion of acromelic acid-containing mushrooms (Clitocybe amoenolens, Clitocybe acromelalga) has resulted in erythromelalgia, a painful peripheral, inflammatory condition. Patients may experience intense burning pain, redness, and edema of the hands and feet, often intensified by heat and relieved by cold. The histopathologic examination of the patient's skin has revealed perivascular mononuclear infiltration and prominent perivascular dermal edema without vasculitis (Diaz, 2005; Saviuc et al, 2001; Benjamin, 1995). NMDA and non-NMDA receptors are present in small unmyelinated sensory nerve endings in the skin; it has been proposed that these peripheral glutamate receptors of skin nerve endings may be the source of pain associated with inflammation (Saviuc et al, 2001)

References

General Bibliography

    1) Benjamin DR: Mushrooms poisons and panaceas: A handbook for naturalists, mycologists and physicians, W. H. Freeman and Company, New York, NY, 1995.
    2) Bessard J, Saviuc P, Chane-Yene Y, et al: Mass spectrometric determination of acromelic acid A from a new poisonous mushroom: Clitocybe amoenolens. J Chromat A 2004; 1055:99-107.
    3) Chyka PA, Seger D, Krenzelok EP, et al: Position paper: Single-dose activated charcoal. Clin Toxicol (Phila) 2005; 43(2):61-87.
    4) Diaz JH: Syndromic diagnosis and management of confirmed mushroom poisonings. Crit Care Med 2005; 33:427-436.
    5) Elliot CG, Colby TV, & Kelly TM: Charcoal lung. Bronchiolitis obliterans after aspiration of activated charcoal. Chest 1989; 96:672-674.
    6) FDA: Poison treatment drug product for over-the-counter human use; tentative final monograph. FDA: Fed Register 1985; 50:2244-2262.
    7) Golej J, Boigner H, Burda G, et al: Severe respiratory failure following charcoal application in a toddler. Resuscitation 2001; 49:315-318.
    8) Graff GR, Stark J, & Berkenbosch JW: Chronic lung disease after activated charcoal aspiration. Pediatrics 2002; 109:959-961.
    9) Harris CR & Filandrinos D: Accidental administration of activated charcoal into the lung: aspiration by proxy. Ann Emerg Med 1993; 22:1470-1473.
    10) Malencon G & Bertault R: Flore des Champignons Superieurs du Maroc. Series Botanique et Biologie Vegetale (translated by Gary Lincoff), 2, 33. Institut Scientifique Cherifien, Faculte des Sciences de Rabat, 1975, pp 138.
    11) Nakajima N, Ueda M, Higashi N, et al: Erythromelalgia associated with Clitocybe acromelalga intoxication. Clin Toxicol (Phila) 2013; Epub:Epub.
    12) None Listed: Position paper: cathartics. J Toxicol Clin Toxicol 2004; 42(3):243-253.
    13) Pollack MM, Dunbar BS, & Holbrook PR: Aspiration of activated charcoal and gastric contents. Ann Emerg Med 1981; 10:528-529.
    14) Rau NR, Nagaraj MV, Prakash PS, et al: Fatal pulmonary aspiration of oral activated charcoal. Br Med J 1988; 297:918-919.
    15) Saviuc P, Dermatteis M, Mezin P, et al: Toxicity of the Clitocybe amoenolens mushroom in the rat. Vet Human Toxicol 2003; 45(4):180-182.
    16) Saviuc PF, Danel VC, Moreau PAM, et al: Erythromelalgia and mushroom poisoning. Clin Toxicol 2001; 39(4):403-407.