A 19-year longitudinal assessment of gyromitrin-containing (Gyromitra spp.) mushroom poisonings in Michigan.

Mushroom poisonings are common in the United States. Gyromitrin (acetaldehyde N-methyl-N-formylhydrazone) is a clinically significant mycotoxin primarily associated with the lorchel (i.e. the false morel) Gyromitra esculenta. Resemblance between 'true and false morels' has resulted in misidentification of Gyromitra spp. as edible and sought after Morchella spp., resulting in toxicity. Despite literature evidence outlining toxic sequalae, Gyromitra spp. mushrooms are commonly consumed and prepared for culinary purposes. Classic clinical teachings emphasize significant neurotoxicity, including seizures, associated with ingestion of gyromitrin-containing mushrooms, stemming from gyromitrin's terminal metabolite monomethylhydrazine. We performed a longitudinal descriptive review of the clinical toxicity associated with ingestion of mushroom species known or suspected to contain gyromitrin in cases reported to the Michigan Poison & Drug Information Center between January 1, 2002, to December 31, 2020. Our 19-year descriptive case series of gyromitrin-containing mushroom ingestions reported to our Center demonstrated a preponderance of gastrointestinal signs and symptoms, including hepatotoxicity. Of 118 identified cases, 108 (91.5%) of the reported ingestions involved Gyromitra esculenta. The most frequent clinical findings associated with symptomatic ingestions (n = 83) were the aforementioned gastrointestinal symptoms (n = 62; 74.7%). Neurological symptoms were less frequent (n = 22, 26.5%) while hepatotoxicity occurred in fewer patients (n = 14; 16.9%). Of symptomatic patients, most were treated with symptomatic and supportive care (n = 58; 70%). Pyridoxine was used in a total of seven patients (n = 7; 8.4%) with either hepatotoxicity or neurotoxicity. Medical outcomes ranged from minor to major, with no reported deaths. Patient presentations (i.e. GI vs. neurotoxic symptoms) following ingestion of gyromitrin-containing mushrooms may be highly variable and multifactorial, owing to differences in dose ingested, geographical distribution, genetic variability of both patient and mushroom species, and species-specific differences in toxin composition. Future research warrants species-level identification of ingested gyromitrin-containing mushrooms and investigating the contribution of genetic polymorphisms to differences in clinical toxidromes.

A network system for the prevention and treatment of mushroom poisoning in Chuxiong Autonomous Prefecture, Yunnan Province, China: implementation and assessment.

BACKGROUND: Mushroom poisoning is a major public health issue in China. The integration of medical resources from different institutes of different levels is crucial in reducing the harm of mushroom poisoning. However, few studies have provided comprehensive implementation procedures and postimplementation effectiveness evaluations. To reduce the harm caused by mushroom poisoning, a network system for the prevention and treatment of mushroom poisoning (NSPTMP) was established in Chuxiong, Yunnan Province, a high-risk area for mushroom poisoning. METHODS: The NSPTMP consists of three types of institutions, namely, centers for disease prevention, hospitals, and health administration departments, with each kind of institution comprising prefecture, county/city, town, and village levels. After three years of implementation, the network was evaluated by comparing the indices before and after network implementation using data from the "Foodborne Disease Outbreak Surveillance System" and 17 hospitals in Chuxiong. The indices included the fatalities caused by mushroom poisoning, the composition ratios of different types of mushrooms for both outpatients and inpatients and the hospitalization rates. RESULTS: Compared to the average fatality rate of mushroom poisoning from 2015 to 2017, the average fatality rate from 2018 to 2020 significantly decreased from 0.57 to 0.06% (P < 0.001). Regarding the poisonous genus containing lethal mushrooms, the outpatient and inpatient composition ratios significantly decreased for Amanita (9.36-2.91% and 57.23-17.68%, respectively) and Russula (15.27-8.41%) (P < 0.05). Regarding poisonous mushrooms that caused mild symptoms, the outpatient and inpatient composition ratios significantly increased for Scleroderma (5.13-13.90% and 2.89-18.90%, respectively) and Boletaceae (19.08-31.71%) (P < 0.05), and the hospitalization rates significantly increased for Scleroderma (6.33-18.02%) and Boletaceae (5.65-12.71%) (P < 0.05). CONCLUSIONS: These findings suggest that the NSPTMP effectively reduced the harm caused by mushroom poisoning. In addition to the integration of medical resources, the development of poisonous mushroom identification, hierarchical treatment systems in hospitals, public education, and professional training also played important roles in improving the system's effectiveness. The establishment and evaluation of the NSPTMP in Chuxiong Prefecture can provide valuable insights and serve as a model for other regions facing similar challenges in managing mushroom poisoning.

Epidemiology and Economic Burden of an Outbreak of Cyclopeptide-Containing Mushroom Poisoning in the West of Iran.

Little evidence is available on the epidemiological and economical dimensions of certain foodborne diseases such as wild mushroom poisoning. This study aimed to investigate the epidemiology and estimate the costs of poisoning with cyclopeptide-containing mushrooms in Kermanshah province in 2018. In this study, poisoning was investigated in different subgroups. The cost of illness method with a bottom-up approach was used to estimate the poisoning costs. Both direct and indirect costs of the poisoning were included in the analysis. The perspective of the study was society. Required data were obtained from the medical records of Imam Khomeini hospital and completed through a line survey with the patients. Two hundred eighty-three patients were poisoned in Kermanshah due to poisoning with cyclopeptide-containing mushrooms. Of 283 patients, 143 (50.53%) were men and 59.01% of patients were rural residents. About 43% of admissions were out-patient cases and ~40% of patients were hospitalized within 1-3 days. Also, eight patients were pronounced dead in the area. The total cost of poisoning with cyclopeptide-containing mushrooms in Kermanshah province was $ 1,259,349.26. Of that, $ 69,281.65 was related to direct medical costs and $ 10,727.23 was direct non-medical costs. The indirect costs of death were estimated to be $ 1,125,829.7. The current study revealed that there is a significant financial burden due to cyclopeptide-containing mushrooms on patients, the health system, and society as a whole. Further studies are recommended to clarify the epidemiological and economic burden of foodborne illnesses related to wild mushroom poisonings. Sharing the outputs with health authorities, and informing the general public are warranted to reduce the burden of such diseases.

Nephrotoxic Mushroom Poisoning: Global Epidemiology, Clinical Manifestations, and Management.

Because mushroom poisonings are increasing worldwide after ingestions of known, newly described, and formerly considered edible species, the objectives of this review are to describe the global epidemiology of nephrotoxic mushroom poisonings, to identify nephrotoxic mushrooms, to present a toxidromic approach to earlier diagnoses of nephrotoxic mushroom poisonings based on the onset of acute renal failure, and to compare the outcomes of renal replacement management strategies. Internet search engines were queried with the keywords to identify scientific articles on nephrotoxic mushroom poisonings and their management during the period of 1957 to the present. Although hepatotoxic, amatoxin-containing mushrooms cause most mushroom poisonings and fatalities, nephrotoxic mushrooms, most commonly Cortinarius species, can cause acute renal insufficiency and failure. Several new species of nephrotoxic mushrooms have been identified, including Amanita proxima and Tricholoma equestre in Europe and Amanita smithiana in the United States and Canada. In addition, the edible, hallucinogenic mushroom Psilocybe cubensis has been noted recently via mass spectrometry as a rare cause of acute renal insufficiency. Renal replacement therapies including hemodialysis are often indicated in the management of nephrotoxic mushroom poisonings, with renal transplantation reserved for extracorporeal treatment failures.

Health Care Utilization and Outcomes Associated with Accidental Poisonous Mushroom Ingestions - United States, 2016-2018.

Accidental consumption of poisonous mushrooms can result in serious illness and death (1). Reports of severe poisonings from consumption of foraged mushrooms for food or hallucinogenic purposes increased during 1999-2016 (2), and approximately 7,500 poisonous mushroom ingestions were reported annually to poison control centers across the United States (1). To estimate the frequency of emergency department (ED) visits, hospitalizations, and severe adverse outcomes associated with accidental poisonous mushroom ingestion in the United States, CDC analyzed 2016 data from the Healthcare Cost and Utilization Project's* Nationwide Emergency Department Sample (HCUP-NEDS) and National Inpatient Sample (HCUP-NIS) databases as well as 2016-2018 data from three IBM MarketScan sources: Commercial Claims and Encounters (CCAE), Medicare Supplemental and Coordination of Benefits (Medicare), and Multi-State Medicaid databases. During 2016, 1,328 (standard error [SE] = 100) ED visits and 100 (SE = 22) hospitalizations (HCUP data) were associated with accidental poisonous mushroom ingestion. Among 556 patients with a diagnosis of accidental poisonous mushroom ingestion, 48 (8.6%) patients experienced a serious adverse outcome during 2016-2018 (MarketScan data). Serious adverse outcomes were more common among Medicaid-insured patients than among patients with commercial insurance or Medicare (11.5% versus 6.7%, p = 0.049). Because most mushroom poisonings are preventable, wild mushrooms should not be consumed unless they are identified by an expert; increased public health messaging about the potential dangers of mushroom poisoning is needed.

Low-cost management of mushroom poisoning in a limited-resource area: a 12-year retrospective study.

Amatoxin poisoning is the main cause of death from accidental ingestion of poisonous mushrooms and a mortality rate of 27.3% has been reported in Thailand. Symptoms of mushroom ingestion are often confused with food poisoning; thus, gastroenteritis is not recognised as the first phase of poisoning. Our study assessed the efficacy of N-acetylcysteine (NAC) as a treatment for amatoxin poisoning. We retrospectively analysed 74 medical records over 12 years. The majority (70/74) were treated successfully with NAC; death in the remaining 4 (5.4%) patients was attributed to late presentation in three and advanced alcoholic cirrhosis in one.

Nicotinic acid treatment for Paralepistopsis acromelalga intoxication: assessment using magnetic resonance imaging.

CONTEXT: Paralepistopsis acromelalga, formerly known as Clitocybe acromelalga, is a rare poisonous mushroom. The mycotoxins in this mushroom cause symptoms resembling those of erythromelalgia; however, its pathogenesis remains unclear. In this report, a patient who received nicotinic acid treatment for P. acromelalga poisoning and radiological evaluation for erythromelalgia has been presented. Case detail: A 59-year-old woman was hospitalized for redness, swelling, and burning pain in her extremities that rendered difficulty in walking, and a diagnosis of P. acromelalga poisoning was made by detailed interview and mushroom identification. She was treated with intravenous nicotinic acid for 17 days followed by oral nicotinic acid amide for 2 months. She exhibited rapid symptomatic improvement and walked independently after 11 days of initial treatment. Initial MRI of her feet revealed toe-dominated subcutaneous thickening. After nicotinic acid treatment, those radiological findings improved dramatically. DISCUSSION: The subcutaneous thickening evident on MRI indicated P. acromelalga poisoning-induced erythromelalgia involved subcutaneous inflammatory edema. The typical duration of edema without treatment is more than a month. The improvement on MRI after nicotinic acid treatment indicated that the adequate vasodilation induced by nicotinic acid contributed to resolution of the symptoms. Nicotinic acid was associated with the improvement of the edematous changes caused by the P. acromelalga intoxication.

Assessment of patients who presented to the emergency department with mushroom poisoning.

OBJECTIVE: This study aimed to assess the demographic characteristics, emergency department (ED) complaints, laboratory findings, and latent phase periods of patients who presented to the ED due to mushroom poisoning (MP) as well as the efficacy of conventional and hemofiltration therapies. METHOD: The study was conducted on patients who presented to the ED with MP between 2010 and 2012. The patient's demographic characteristics, complaints at the ED, latent phases, laboratory findings, and treatments of MP cases were evaluated. RESULTS: The mean age of patients was 38.03 ± 15.96, where 63.8% of them were female and 36.2% were male. Visits occurred most frequently in the autumn (32.6%). When presenting to the ED, the most frequent complaint was nausea-vomiting. The aspartate aminotransferase (AST), alanine aminotransferase (ALT), international normalised ratio (INR), and blood urea nitrogen values of patients with a latent phase between 0 h and 5 h were significantly lower than the values of patients with a latent phase between 6 h and 24 h. In this study, 62% of the patients (n = 36) had stomach lavage and received activated charcoal. Altogether, 55.2% of the patients had received conventional therapy, 37.9% of them received hemofiltration, and all of them received supportive treatment. The AST, ALT, and INR values of those who had received hemofiltration and conventional therapies were significantly higher than of those who received only supportive treatment (p < 0.01). CONCLUSION: Hemofiltration, in combination with conventional therapy, seems to be an effective treatment for reducing mortality in suspected MP cases involving late acting toxins.

[Trends of food poisonings caused by natural toxins in Japan, 1989-2011].

In order to reduce the health risk associated with food poisonings caused by natural toxins, it is necessary to implement risk management strategies based on previous poisoning data and risk factors. In present study, we statistically analyzed natural toxin food poisoning (NTFP) data published by the Ministry of Health, Labour and Welfare from 1989 to 2010 in Japan and reviewed the trends of NTFP for each natural toxin hazard. Since 1989, the number of incidents of NTFP in each year has not been reduced. Prevention and control are needed to reduce the risk of NTFP. The major site for all hazards was "at home". This result suggested that consumer education is critically important to inform about NTFP occurrence, preventive measures and emergency treatments. Furthermore, countermeasures for NTFPs which have never occurred in the past in Japan should be considered, because of the increasing variety of imported foods and changes resulting from the inerease of sea temperature with global warming.

Assessment of emergency liver transplantation criteria in acute liver failure due to Amanita phalloides.

BACKGROUND AND AIMS: The emergency liver transplantation criteria for acute liver failure (ALF) due to Amanita phalloides (A. phalloides) intoxication are not consensual. The aims of this study were to evaluate the clinical outcomes, and to assess the accuracy of the current and specific criteria for emergency liver transplantation in predicting fatal outcome in ALF induced by A. phalloides. METHODS: Ten patients admitted with ALF induced by A. phalloides in a Gastroenterology Intensive Care Unit were studied. Indications for liver transplant were based on Clichy and/or King's College criteria. Specific criteria of Ganzert and Escudié were tested retrospectively. RESULTS: A. phalloides intoxication represented 11.6% of all admissions for ALF. Patients were admitted at a mean time of 60 ± 20.4 h after ingestion. Eight patients met the Clichy and/or King's College criteria for emergency liver transplantation, seven of these patients were listed for transplant and only six patients were transplanted. Four (40%) patients died in a mean time of 4.8 ± 0.74 days after ingestion. When applied retrospectively, Escudié's criteria showed 100% of accuracy for predicting fatal outcome, whereas, King's College, Clichy's and Ganzert's criteria had an accuracy of 90, 80 and 70%, respectively. A prothrombin index of less than 10% at day 3 after ingestion showed a positive predictive value of 100% and a negative predictive value of 60%. CONCLUSION: Escudié's criteria show the best accuracy for emergency liver transplant in ALF induced by A. phalloides. The assessment of these criteria at day 3 after ingestion shows a maximum positive predictive value, although with a decline in its negative predictive value.

Amatoxin poisoning treatment decision-making: pharmaco-therapeutic clinical strategy assessment using multidimensional multivariate statistic analysis.

Ninety percent of fatal higher fungus poisoning is due to amatoxin-containing mushroom species. In addition to absence of antidote, no chemotherapeutic consensus was reported. The aim of the present study is to perform a retrospective multidimensional multivariate statistic analysis of 2110 amatoxin poisoning clinical cases, in order to optimize therapeutic decision-making. Our results allowed to classify drugs as a function of their influence on one major parameter: patient survival. Active principles were classified as first intention, second intention, adjuvant or controversial pharmaco-therapeutic clinical intervention. We conclude that (1) retrospective multidimensional multivariate statistic analysis of complex clinical dataset might help future therapeutic decision-making and (2) drugs such as silybin, N-acetylcystein and putatively ceftazidime are clearly associated, in amatoxin poisoning context, with higher level of patient survival.

[The assessment of albumin liver dialysis--MARS efficacy in the treatment of Amanita phalloides poisoning]. / Ocena skutecznosci albuminowej dializy watroby--MARS w terapii zatruc muchomorem sromotnikowym.

Fourteen patients were included to the albumin dialysis--MARS in the Clinic of Internal Medicine Geriatry and Clinical Toxicology in the years 2004-2006 because of acute intoxication with Amanita phalloides. The 26 procedures were done. Ten patients recovered, one was transplanted and three patients at the age from 68 to 79 (average 72.6) years died because of acute liver failure (21.4% cases). All deceased patients had significant higher plasma bilirubin level and INR in compare to other probants. The procedures of albumin dialysis caused significant lowering of blood glucose level, red blood cells and platelets, but without the need for intervention.

Evolving global epidemiology, syndromic classification, general management, and prevention of unknown mushroom poisonings.

OBJECTIVE: To assess the evolving global epidemiology of mushroom poisoning and to identify new and emerging mushroom poisonings and their treatments, a descriptive analysis and review of the world's salient scientific literature on mushroom poisoning was conducted. DATA SOURCE: Data sources from observation studies conducted over the period 1959-2002 and describing 28,018 mushroom poisonings since 1951 were collected from case reports, case series, regional descriptive studies, meta-analyses, and laboratory studies of mushroom poisonings and the toxicokinetics of mycotoxins. STUDY SELECTION: Studies included in the review were selected by a MEDLINE search, 1966-2004, an Ovid OLDMEDLINE search, 1951-1965, and a medical library search for sources published before 1951. DATA EXTRACTION: To better guide clinicians in establishing diagnoses and implementing therapies, despite confusing ingestion histories, data were extracted to permit an expanded syndromic classification of mushroom poisoning based on presentation timing and target organ systemic toxicity. DATA SYNTHESIS: The final 14 major syndromes of mushroom poisoning were stratified first by presentation timing and then by target organ systemic toxicity and included early (<6 hrs), late (6-24 hrs), and delayed syndromes (> or =1 day). There were eight early syndromes (four neurotoxic, two gastrointestinal, two allergic); three late syndromes (hepatotoxic, accelerated nephrotoxic, erythromelalgia); and three delayed syndromes (delayed nephrotoxic, delayed neurotoxic, rhabdomyolysis). Four new mushroom poisoning syndromes were classified including accelerated nephrotoxicity (Amanita proxima, Amanita smithiana), rhabdomyolysis (Tricholoma equestre, Russula subnigricans), erythromelalgia (Clitocybe amoenolens, Clitocybe acromelalgia), and delayed neurotoxicity (Hapalopilus rutilans). In addition, data sources were stratified by three chronological time periods with >1,000 confirmed mushroom ingestions reported and tested for any statistically significant secular trends in case fatalities from mushroom ingestions over the entire study period, 1951-2002. CONCLUSIONS: Since the 1950s, reports of severe and fatal mushroom poisonings have increased worldwide. Clinicians must consider mushroom poisoning in the evaluation of all patients who may be intoxicated by natural substances. Since information on natural exposures is often insufficient and incorrect, a new syndromic classification of mushroom poisoning is recommended to guide clinicians in making earlier diagnoses, especially in cases where only advanced critical care, including organ transplantation, may be life saving.

The epidemiology, toxidromic classification, general management, and prevention of mushroom poisoning in the United States.

Since the 1950s, reports of severe and fatal mushroom poisonings have increased worldwide. Clinicians must consider mushroom poisoning in the evaluation of all patients who may be intoxicated by natural substances. Because information on natural exposures is often incorrect or insufficient, a new syndromic classification of mushroom poisoning is proposed to guide clinicians in making earlier diagnoses, especially in cases where only advanced critical care, including kidney or liver transplantation, may be life saving.

Analysis of amatoxins alpha-amanitin and beta-amanitin in toadstool extracts and body fluids by capillary zone electrophoresis with photodiode array detection.

Over 90% of the lethal cases of mushroom toxin poisoning in man are caused by a species of amanita. The amatoxins (especially alpha- and beta-amanitin) found in amanita deserve special attention, because of their high pharmacological potency, their high natural concentration and their high chemical and thermal stability. Measures can be taken to improve the survival rates (aggressive gastroenteric decontamination, liver protection therapy) if the poisoning is diagnosed correctly and as early as possible. The standard assay for alpha-amanitin is a radioimmunoassay (RIA). Among other reagents, this assay uses 125I-labelled alpha-amaintin, which has a low shelf life. The assay is therefore not available at all hospitals and all year round. In this paper, a first attempt to employ capillary zone electrophoresis (CZE) to quantify amatoxins alpha- and beta-amanitin in urine samples of afflicted patients and in toadstool extracts is described. Diode array detection is used for identification of the resolved substances in the electropherogram. An analysis requires 20 min. The detection limit is 1 microgram/ml, i.e., 5 pg absolute. Relative standard deviations are between 1 and 2% for the calibration standards (peak height and area) and ca. 7.5% for the real samples. Advantages of the CZE over the RIA include lower cost, the possibility of quantifying several toxins in one analysis, less consumption of potentially harmful reagents (no radio-labelled substances, no addition of alpha-amanitin as reagent) and, most importantly, all-year-round availability of the assay. The detection limit is still somewhat high and does not cover the entire clinically relevant range. Attempts to lower the detection limit by the necessary order of magnitude are currently under way in our laboratory. These include application of laser-induced fluorescence detection, liquid chromatography-CZE and CZE-mass spectrometry techniques.

Assessment of a general therapeutic protocol for the treatment of acute T-2 toxicosis in swine.

T-2 toxin, a trichothecene mycotoxin suspected of being used as a chemical warfare agent, was administered iv to swine at a dose of 3.6 mg/kg body weight (iv LD50 approximately 1.2 mg/kg). Four different therapeutic protocols were assessed for their efficacy in the treatment of the resultant acute T-2 toxicosis syndrome. One therapeutic protocol included the combined use of metoclopramide, activated charcoal, magnesium sulfate, dexamethasone sodium phosphate, sodium bicarbonate and normal saline. The other 3 protocols utilized the same agents less 1 of the following: the combination of activated charcoal and magnesium sulfate, sodium bicarbonate, or normal saline. All 4 treatment groups showed improved survival times compared to a positive T-2 control group. Within the limits of the study, it would appear that the removal of activated charcoal and magnesium sulfate was most detrimental to the T-2 toxin-dosed swine.

Assessment of potential therapies for acute T-2 toxicosis in the rat.

The efficacy of a variety of approaches for the treatment of animals with acute T-2 toxicosis was assessed utilizing young female rats. A single large dose of the water soluble salt of methylprednisolone significantly prolonged survival times in T-2 toxin treated animals. The use of diltiazem hydrochloride, dazemgrel, N-acetylcysteine, dimethyl sulfoxide, adenosine triphosphate (ATP), ATP combined with magnesium chloride, ascorbic acid, and aprotinin did not prolong survival times at the dosages administered. Trichodermin, a trichothecene similar in structure and biochemical activity to T-2 toxin but much less acutely toxic, had a detrimental effect on survival times whether given 1 hr prior to or after T-2 toxin.