Amatoxin: A review

This article presents a comprehensive review of amatoxin poisoning. The article discusses the biochemistry of amatoxin, as well as the clinical manifestations of amatoxin ingestion. In addition, the evaluation of the patient with amatoxin ingestion is discussed, along with the treatment – including newer therapy – and the ultimate prognosis of the syndrome. *Corresponding author: Bobby Desai, Department of Emergency Medicine, University of Florida, P.O Box 100186, Gainesville, FL, USA 32610, Tel:352265-5911; Fax:352-265-5606, E-mail: [email protected] Received March 17, 2012; Accepted March 27, 2012 Published March 29, 2012 Citation: Bobby Desai BA, Lisenbee N (2012) Amatoxin: A review. Emergency Medicine 2:110. doi:10.4172/2165-7548.1000110 Copyright: © 2012 Bobby Desai BA, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Introduction The United States contains over 5,000 species of mushrooms. While 4-6% of U.S. mushroom species are safe to eat, approximately 2% are poisonous, with twelve species being known to be fatal if ingested. Worldwide, accurate figures for the incidence of mushroom toxicity are difficult to obtain. Outbreaks of severe mushroom poisoning have been documented in Europe, Russia, the Middle East, and the Far East. In all of these areas, mushroom foraging is a common practice. Ninety percent of deaths from mushroom ingestions are due to amatoxin, which possesses a fatality rate of up to 25% when ingested. In 2007, 45 cases of amatoxin poisoning were reported in the United States, with only one documented death. The difficulty in the treatment of amatoxin poisoning lies in partto the lack of both an effective antidote and a standardized accepted treatment for this poisoning. On a molecular level, amatoxin and its effects on downstream physiologic targets is just beginning to be understood, thus leading to the lack of progress in therapeutic options for amatoxin poisoning [1].The majority of reported amatoxin ingestions fall in a few specific categories, such as accidental ingestions in young children or wild mushroom foragers and intentional ingestions in patients attempting suicide or seeking the drug for its hallucinatory effects [1]. In terms of biochemical categorization, amatoxin exists as a heat-stable toxin, which allows it to maintain its three-dimensional structure at elevated temperatures. Increasing amatoxin’s toxicity is the fact that it is not susceptible to enzymatic hydrolization. Amatoxin exists in multiple subtypes, with alpha and beta being the common, and all subtypes are not water soluble. Through the mechanism of mRNA inhibition, amatoxin is able to inhibit DNA dependent RNA polymerase B which leads to a wide range of tissue injury, most notably to the intestinal mucosa, liver, and kidneys. Enterohepatic circulation followed by renal reabsorption delivers the toxin to these tissues. In terms of toxicity, there are reported cases of amanita poisoning and toxicity with ingestions as small as 30 grams of Amanita phalloides[2]. Many species of mushrooms contain amatoxin. For example, Aminitaphalloides, known as the “Death Cap,” Amanita verna, known as the “Fool’s Mushroom,” and Amanita virosa and Amanita bisporigera, a complex known as the “Destroying Angel,” all contain alpha-amanitin. Galerinaautumnalis, known as the “Autumn Skullcap,” contains beta-amanitin and gamma-amanitin, which are believed to be less toxic than their alpha-subtype counterpart[3]. It is well-known that amatoxin primarily causes death through the process of fulminant hepatic failure secondary to liver parenchymal necrosis.Zhou et al. created the first acceptable large animal model for fulminant hepatic failure through exposure to intraperitoneal infusions of amatoxin and endotoxin. Liver biopsy revealed extensive hepatocyte steatosis and parenchymal necrosis at as early as 36 hours after amatoxin administration. Extrahepatic manifestations were confirmed in the form of hepatic encephalopathy as seen on MRI and autopsy. The authors of this study confirmed that fulminant hepatic failure is a rapid and progressive pattern of disease that is important to understand for any suspected amatoxin poisoning [3]. Clinical Presentation The pattern of injury following amatoxin ingestion presents in three phases. The first phase consists of ingestion and the appearance of initial symptoms within the first 24 hours, with the majority of patients being symptomatic within the first 15 hours. The constellation of symptoms involved in phase one include nausea, vomiting, watery diarrhea, and abdominal pain, which may be confused for cholera, gastroenteritis, or food poisoning depending on the clinical scenario. In general, gastrointestinal symptoms resolve in the beginning of the second phase, which typically begins around 24 hours after ingestion. As phase two progresses, renal and hepatic dysfunction dominates the clinical picture. The temporary resolution of symptoms early in phase two often leads to premature hospital or emergency department discharge. Within days, this group of patients often present back to the emergency department in hepato-renal failure with clinically evident jaundice. The third and final phase of amatoxin poisoning occurs three to five days post-ingestion and consists of further progression of renal and hepatic failure. Without focused care, phase three can lead to shock, multi-organ failure, and death [4]. These patients often will require an emergency liver transplant (Figure 1).