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Treatment of Amatoxin Poisoning: 20-Year Retrospective Analysis
Abstract
Background:
Amatoxin poisoning is a medical emergency characterized by a long incubation time lag, gastrointestinal and hepatotoxic phases, coma, and death. This mushroom intoxication is ascribed to 35 amatoxin-containing species belonging to three genera: Amanita, Galerina, and Lepiota. The major amatoxins, the alpha-, beta-, and gamma-amanitins, are bicyclic octapeptide derivatives that damage the liver and kidney via irreversible binding to RNA polymerase II.
Methods:
The mycology and clinical syndrome of amatoxin poisoning are reviewed. Clinical data from 2108 hospitalized amatoxin poisoning exposures as reported in the medical literature from North America and Europe over the last 20 years were compiled. Preliminary medical care, supportive measures, specific treatments used singly or in combination, and liver transplantation were characterized. Specific treatments consisted of detoxication procedures (e.g., toxin removal from bile and urine, and extracorporeal purification) and administration of drugs. Chemotherapy included benzylpenicillin or other beta-lactam antibiotics, silymarin complex, thioctic acid, antioxidant drugs, hormones and steroids administered singly, or more usually, in combination. Supportive measures alone and 10 specific treatment regimens were analyzed relative to mortality.
Results:
Benzylpenicillin (Penicillin G) alone and in association was the mostfrequently utilized chemotherapy but showed little efficacy. No benefit was found for the use of thioctic acid or steroids. Chi-square statistical comparison of survivors and dead vs. treated individuals supported silybin, administered either as mono-chemotherapy or in drug combination and N-acetylcysteine as mono-chemotherapy as the most effective therapeutic modes. Future clinical research should focus on confirming the efficacy of silybin, N-acetylcysteine, and detoxication procedures.
... Several antidotes are used, such as hormones (insulin, growth hormone, glucagon) steroids, vitamin C, vitamin E, cimetidine, thioctic acid, antibiotics (benzylpenicillin, ceftazidime), N-acetylcysteine, and silybin. From these, only thioctic acid, benzylpenicillin, ceftazidime, N-acetylcysteine, silybin, and cimetidine have been used in the pharmacologic management of amatoxin poisoning with varying success (Enjalbert et al., 2002). ...
... As monotherapy or in combination with other drugs, benzylpenicillin (Figure 8) and other -lactam antibiotics have been the most commonly used drugs in the treatment of amatoxin poisoning. However, the US Food and Drug Administration (FDA) has not authorized benzylpenicillin for the treatment of amanita poisoning (Enjalbert et al., 2002). ...
... Ceftazidine (Figure 9), a third-generation cephalosporin, has been significantly more effective than benzylpenicillin with fewer side effects. This antidote was the second most commonly used β-lactam, always in conjunction with silybin (Enjalbert et al., 2002). ...
Mushroom consumption is a worldwide custom that continues to grow in popularity. On the other hand, foraging for wild mushrooms can lead to serious disease and even death if deadly mushrooms are accidentally consumed. Mushroom poisoning is difficult to diagnose and treat since the symptoms are similar to those of other disorders. In terms of chemistry, mushroom poisoning is associated with extraordinarily strong toxins, meaning that isolating and identifying toxins has substantial scientific relevance, especially in understanding the lethal components of toxic mushrooms. Most of these toxins exhibit exceptional physiological features that might help enhance chemistry, biochemistry, physiology, and pharmacology research. Despite the discovery of more than 100 poisons, several dangerous mushrooms remain unexplored. This review covers the chemistry (including chemical structures, complete synthesis, and biosynthesis), as well as the toxicology, namely the toxicokinetics, mechanisms of toxicology, and clinical toxicology of these poisons, in addition to the discussion of the development of their most effective diagnostic and therapeutic strategies with the hopes of spurring additional studies, focusing on individual classes of toxins found in poisonous mushrooms such as amatoxins, gyromitrin, orellanine, and phallatoxins.
See also the graphical abstract(Fig. 1).
... Amanita phalloides, also known as the "death cap", is responsible for more than 90 % of deaths related to mushroom poisoning. The mortality rate after amanita phalloides poisoning ranges from 10 to 20 % [6]. The clinical symptoms of amanita phalloides poisoning go through four stages [7,8]. ...
Amanita phalloides poisoning, renowned for its high mortality rates, is one of the most serious food safety issue in certain regions worldwide. Assessment of prognosis and development of more efficacious therapeutic strategies are critical importance for amanita phalloides poisoning patients. The aim of the study is to establish a nomogram to predict the clinical outcome of amanita phalloides poisoning patients based on the independent risk factor for prognosis. Herein, between January 2013 and September 2023, a cohort of 149 patients diagnosed with amanita phalloides poisoning was enrolled and randomly allocated into training and validation cohorts, comprising 102 and 47 patients, respectively. Multivariate logistic regression analysis was performed to identify the independent risk factors for morality of amanita phalloides poisoning patients in training cohort. Subsequently, a nomogram model was constructed to visually display the risk prediction model. The predictive accuracy of nomogram was verified by the validation cohort. The C index, the area under the receiver operating characteristic curve (AUC), and calibration plots were used to assessed the performance of nomogram. The clinical utility was evaluated by decision curve analysis (DCA). In the present study, the results showed that hepatic encephalopathy (HE), upper gastrointestinal bleeding (UGB), AST, and PT were the independent risk factors associated with the mortality of amantia phalloides poisoning patients. We constructed a new nomogram to evaluate the probability of death induced by amantia phalloides poisoning. The AUC for the prediction accuracy of the nomogram was 0.936 for the training cohort and 0.929 for the validation cohort. The calibration curves showed that the predicted probability matched the actual likelihood. The results of the DCA suggested that the nomogram has a good potential for clinical application. In summary, we developed a new nomogram to assess the probability of mortality for amanita phalloides poisoning patients. This nomogram might facilitate clinicians in making more efficacious treatment strategies for patients with amanita phalloides poisoning.
... most critical intoxications, such as those by amatoxins and orellanins [37,38], while they lack for syndromes considered less severe as the purely gastroenteric manifestations. The time between ingestion and the onset of symptoms is the first and easiest element one should consider to identify the probable intoxication severity. ...
Fungi are often considered a delicacy and are primarily cultivated and harvested, although numerous species are responsible for intoxication due to toxin content. Foodborne diseases are a significant public health concern, causing approximately 420 000 deaths and 600 million morbidities yearly, of which mushroom poisoning is one of the leading causes. Epidemiological data on non-cultivated mushroom poisoning in individual countries are often unrepresentative, as intoxication rarely requires emergency intervention. On the other hand, the lack of specialist knowledge among medical personnel about the toxicological manifestations of mushroom consumption may result in ineffective therapeutic interventions. This work aims to provide an easy-to-consult and wide-ranging tool useful for better understanding the variability of mushroom intoxications, the associated symptoms, and the main treatments for the most severe cases, given the absence of a complete species mapping tool toxic. Moreover, we establish an effective collection network that describes the incidence of mushroom poisonings by reporting the species and associated toxicological manifestations for each case. In conclusion, we highlight the need to establish appropriate primary prevention interventions, such as training the affected population and increasing consultancy relationships between mycological experts and specialised healthcare personnel.
https://academic.oup.com/mmy/article-abstract/doi/10.1093/mmy/myae033/7640032?utm_source=etoc&utm_campaign=mmy&utm_medium=email
Se estudió la resistencia a la corrosión de recubrimientos de conversión sobre acero en presencia de solución de NaCl 0,6 M. Las propiedades y eficacia de estos recubrimientos fueron evaluadas mediante distintas técnicas electroquímicas y su morfología superficial fue observada y registrada fotográficamente con una lupa estereoscópica.
The intake of mushrooms has increased recently, for various health reasons. Furthermore, some people ingest particular mushrooms for their hallucinogenic properties, which has resulted in a rise in mushroom poisonings. Particularly, eating of mushrooms collected from the wild may have significant potenteil of exposing consumers to hazardous levels of poisoning. This book chapter reviews the health, nutritive values and noxious substances present in mushrooms. The chapter also will provide information to consumers to assitst in the early detection, investigation, and treatment of mushroom contaminants. Finally, the chapter informs the consumer on how to avoid mushroom poisoning in everyday life. Pleurotus florida, a delightful edible fungus with significant medicinal potential that is widely produced on an economical basis in several parts of the world, belongs to the genus Pleurotus. Amatoxin poisoning, which leads to hepatocellular damage, is a serious problem in the health system in certain countries and could among the commonest reasons for liver transplantation.
Analysis of two mushroom poisonings and their sequelae emphasizes the uncertainties often experienced in such cases, and alerts the mycological community to a new and potentially life-saving treatment, plasmapheresis.
Twenty-five carpophores were sampled and the influence of various factors on concentration and distribution of principal neutral (phalloin, phalloidin, phallisin) and acid (phallacidin and phallisacin) phallotoxins in Amanita phalloides was investigated. The nature of the organ investigated is stressed; for phallotoxins, the volva is most toxic. In addition, specimens collected from ordinary lowland countryside contained twice the toxin quantities as those from a medium altitude site; these quantities depend on a high neutral molecule content and particularly phalloidin. Substantial variations in toxin levels between two consecutive collection operations during the mushroom season were also observed whatever the collection site. This indicated a fall in these values at the end of the seasonal cycle. Although toxin levels depended on collection date, predominance of neutral or acid molecules remained constant. Phallotoxin levels also varied by various stages of carpophore development. In specimens from the plain, this resulted in a different distribution of neutral and acid toxins at maturity. Determination of toxin levels at various stages of maturation varied according to the specimens analyzed.
A 62-year-old woman and her 67-year-old husband suffered, in June 1994, from Amanita phalloides poisoning. This is an unusually early time of the year for these mushrooms to appear. The patients were successfully treated with intensive supportive therapy and with intravenous application of penicillin and silibinin (Legalon SIL). After 12 and 15 days of treatment, respectively, the patients could leave the hospital. Our investigation demonstrates the efficiency of intensive supportive and medical therapy with penicillin and silibinin. After an analysis of the existing literature, we recommend the immediate application of penicillin and silibinin if Amanita phalloides poisoning occurs. It has not yet been proved whether there are any benefits in using hemodialysis or hemoperfusion in the early stages in Amanita phalloides poisoning.
The case described is a serious parasuicide (failed suicide) by voluntary ingestion of a considerable amount of highly poisonous mushrooms (Amanita phalloides). The liver transplant performed straight afterwards enabled the patient to survive, but after a period of relative well-being in the immediate postoperative period, her pervasive suicidal ideation returned to the fore in all its dramatic ambivalence. The difficulties involved in managing the case and the decision to transplant a living organ in an individual who has just attempted suicide are discussed.
There are many species of poisonous mushrooms, but in the United States most poisoning is due to the Amanita. More than 100 deaths result each year from consumption of wild poisonous mushrooms. 90 percent being due to A. phalloides (death cap) or closely related species. Fatalities have occured after ingestion of only part of one mushroom. A. phalloides, A. virosa (destroying angel), some other Amanita species, and Galeria venenata contain heat-stable cyclopeptide cytotoxins which are rapidly bound to tissues. The principal toxin is alfa-amanitin, which binds to and inhibits specifically the mammalian RNA polymerase responsible for messenger RNA synthesis. Ingestion of these dangerous mushrooms is followed by a latent period of 6 to 20h. Manifestations of cytotoxicity then may appear suddenly and consist of severe nausea, violent abdominal pain, bloody vomiting and diarrhea, and cardiovascular collapse. Headache, mental confusion, coma, or convulsions are common. Painful and tender hepatomegaly, jaundice, hypoglycemia, dehydration, and oliguria or anuria frequently appear on the first or second day after ingestion. Ingestion of other poisonous mushrooms may cause gastrointestinal symptoms, visual disturbances, ataxia, disorientation, convulsions, coma, fever, hemolysis, and methemoglobinemia. Treatment of mushroom poisoning depends upon the species ingested. If parasympathomimetic manifestations are prominent, atropine in doses of 1 to 2 mg given intramuscularly and repeated every 30 min until symptoms are controlled. Poisoning by cytotoxic mushrooms in treated mainly symptomatically. Fluid and electrolyte balance must be carefully maintained. Hypoglycemia should be avoided; large quantities of carbohydrate may exert some protective effect on the liver. Excitement convulsions pain, hypotension, and fever may need symptomatic therapy.