MUSHROOMS INTOXICATIONS

Purpose: To perform a retrospective analysis of mushroom poisonings in Varna region for 25 years (19912015). Mushroom poisonings account for 10.7% of hospitalizations associated with acute exogenous intoxication. Poisoning with Amanita phalloides, Amanita pantherina, Amanita muscaria and various fungi that cause only gastrointestinal symptoms are of greatest importance for the clinical toxicology in the Republic of Bulgaria. Material/Methods: Objects of the study were 1872 patients who received treatment at the Clinic for Intensive Treatment of Acute Intoxications and Toxicoallergies, Naval Hospital – Varna, Military Medical Academy, Bulgaria after eating mushrooms. Results: Patients with irritative gastroenteritis – 1703 (91%) were with the highest frequency, followed by those with Amanita phalloides intoxication 147 (7.8%). Amanita phalloides poisonings are not common and have a low relative share to all mushroom intoxications, but they are characterized by severe course and high lethality. Poisonings with Amanita pantherina and Amanita muscaria are even less common – 22 (1.2%). Patients accepted for treatment were both male (50.5%) and female (49.5%). Patients in age between 25 and 60 years were prevalent – 1171 (62.6%). A fatal outcome was registered in only 25 patients with Amanita phalloides intoxications, which represents 17% of all patients with Amanita phalloides poisoning and 1.3% of all patients with mushroom intoxications. Conclusion: Mushroom poisonings causing irritant gastroenterocolitis and those with Amanita pantherina and Amanita muscaria have a good prognosis. Amanita phalloides intoxications are characterized by the development of life-threatening organ damages and high lethality.


INTRODUCTION
Poisonings with mushrooms have an important position in the ethology of acute exogenous intoxication and are one of the main reasons for hospitalization.They occur throughout the world, including the Balkan Peninsula.In Turkey, mushroom poisoning comprises the main part of the plant and fungal toxicities [1].The most important mushroom poisoning for toxicological practice in Southeast Europe is those with Amanita phaloides mushrooms.Mushroom poisoning by Amanita phalloides is a rare but potentially fatal disease [2].Death cap (Amanita phalloides) poisoning is a serious medical condition, causing organ failure with potentially fatal outcome [3].It is a toxic mushroom responsible for the majority of deaths occurring after mushrooms ingestion [4,5].Amanita phalloides is the most dangerous, poisonous mushroom species.It is the cause of 90-95% of all deaths due to mushroom poisoning [6,7].Mushroom poisonings with fly agaric (Amanita muscaria) and panther cap (Amanita pantherina) are rather rare [8] and have a good prognosis [9][10][11].
In this regard, we aimed to examine the mushroom poisonings in Varna region for 25 years -from 1991 to 2015, analysing their frequency, distribution by sex and age, clinical course, therapeutic behaviour and lethality.

MATERIALS AND METHODS
The objects of the study were 147 patients treated at the Clinic for Intensive Treatment of Acute Intoxications and Toxicoallergies, Naval Hospital -Varna, Military Medical Academy, Bulgaria.The study was a retrospective covering 25 year period .The histories of disease, personal ambulant cards of the accepted for treatment patients and medico-legal protocols from autopsies of the deceased patients were analysed.The diagnosis was based on a history of consumption of mushrooms, the presence of a latent period of varying duration, clinical symptoms and interpretation of laboratory test results.https://doi.org/10.5272/jimab.2018241.1887

RESULTS AND DISCUSSION
During the 1991-2015 period, in the Clinic of toxicology 1872 patients with mushroom poisoning have received treatment.Their relative share to all patients with acute intoxication is 10.7%.We classified poisonings with mushrooms into 3 groups according to etiological indication: • mushrooms that cause irritative gastroenteritis; • Amanita phalloides intoxications; • intoxications with Amanita pantherina, and Amanita muscaria.
Mushroom poisoning causing irritative gastroenteritis were with the highest frequency -1703 (91%).Here are included patients who have consumed edible mushrooms, but due to the presence of concomitant diseases of the gastrointestinal tract, such as ulcer disease, chronic gastritis and colitis have developed symptoms characteristic of the mushroom poisoning.Consumption of mushrooms containing a lot of hardly digestible substances is an error in the diet for those patients.On the second position by frequency are patients with Amanita phalloides intoxications -147 (7.8%).Poisonings with Amanita pantherina and Amanita muscaria were most rarely observed -22 cases (1.2%).
All poisoning with Amanita phalloides, Amanita pantherina, and Amanita muscaria are the result of the consumption of wild mushrooms instead of edible ones.The toxicity of Amanita phalloides is due to two groups of toxins -phallotoxins and amatoxins.Phallotoxins damage the cell membrane of enterocytes and cause manifestations of the gastrointestinal tract -nausea, vomiting, and diarrhoea.Amatoxins -alpha-, beta-and gammaamanitin are resistant to high temperatures, and alphaamanitin has the highest toxicity [1,10,13,14].Intestinal mucosa, hepatocytes and proximal tubules of the kidney are the main target structures which are damaged by toxins of Amanita phalloides mushrooms [4,15,16,17].Amatoxins directly interact with the enzyme RNA polymerase II in eukaryotic cells, inhibit transcription, prevent protein synthesis and cause cell death [15,18].The main toxins of Amanita pantherina and Amanita muscaria are ibotenic acid and muscimol [19,20].They are rapidly absorbed in the gastrointestinal tract and cause psychotropic effects [10,11].Ibotenic acid acts as an excitatory amino acid at the glutamate receptors, and muscimol acts as an agonist of the gamma-aminobutyric acid receptors [21].Male patients were 945 (50.5%) and prevailed insignificantly over the female -927 (49.5%).The analysis of the distribution of mushroom intoxications by age indicates that the most affected age group was from 25 to 44 years -634 cases (33.2%) and the frequency in patients up to 24 years was very low (20.2%), as well as in patients above 60 years (17.2%)-Table 1.The majority of mushroom intoxications were in the age range from 25 to 60 years -1171 cases (62.6%).

Tabl. 1. Distribution of Amanita intoxication by age
Mushroom poisonings in Bulgaria are most often in late spring, summer and autumn in relation to climatic conditions.In the period from August to November were recorded 1248 cases (66.7%).The peak of intoxications with mushrooms was in October when 35.4% of all poisonings were recorded -Table 2.

Tabl. 2. Distribution of mushroom intoxication by months
Clinical features, course and prognosis of mushroom poisonings are different.They are determined mainly by the species of poisonous mushroom.Mushroom intoxications with irritant gastroenteritis are characterized by mild and short gastrointestinal syndrome.The prognosis is favourable.
Intoxication with Amanita phalloides is ongoing in four phases.a) Asymptomatic lag phase -from the time of ingestion of mushrooms to the appearance of the first symptoms.It continues from 6 to 40 hours [15,18] d) Acute liver failure -characterized by high levels of transaminases, hyperbilirubinemia, coagulopathy, hepatic encephalopathy, hepatorenal syndrome and acute renal failure.Hepatorenal phase begins after 2-3 days.
Intoxications with Amanita pantherina and Amanita muscaria begin after a short latency period, usually from 30 minutes to 2 hours [8,10].They are characterized by nausea, vomiting, hallucinations growing psychomotor agitation, tachycardia, hypertension, mydriasis, redness of the skin.Acute respiratory failure and comatose state are observed very rarely.Prognosis of the poisoning is generally good and lethal cases are rare [9,11,21,22].
Active treatment begins immediately after the patient's hospitalization and diagnosis.The treatment of mushroom poisoning with irritative gastroenterocolitis and the poisoning with Amanita pantherina and Amanita muscaria includes gastrointestinal tract decontamination, venous infusions for rehydration and symptomatic treatment [9].Hallucinations and psychomotor agitation are controlled with benzodiazepines and/or neuroleptics.If small muscarinic symptoms prevail, small doses of atropine are administered [23].
The recommended therapeutic regimen for Amanita phalloides poisoning includes gastrointestinal decontamination procedures, rehydration, metabolic acidosis and electrolyte correction, specific therapies (silibinin, Nacetylcysteine, penicillin G, MARS) and liver transplantation [4,6,13,15,24,25].In Bulgaria, silibinin, MARS and Emergency Liver Transplantation were not available during the study period.In all patients hospitalized up to the 36 th hour after consumption, extracorporeal treatment methods were used -hemodialysis, hemosorbtion or plasmafiltration, although there is no conclusive evidence of their effectiveness in the literature [26,27].After the 4 th day, hyperbaric oxygenation for faster hepatocyte regeneration was applied.Our experience indicates that the protocol used in our Toxicology unit is effective for amatoxin poisoning because although not all recommended methods are available in Bulgaria, the rate of cured patients is as high as the average for Europe.
A lethal outcome was recorded in only 25 patients with Amanita phalloides intoxication, which represents 17% of the patients with such poisoning and 1.3% of all mushroom intoxications.The lethality in the Amanita phalloides intoxications is high and reaches 20% [6, 18,28,29] or 30% in adults and up to 50% in children [4,7].According to our data, Amanita phalloides mushrooms cause 11.4% of lethality in acute poisoning cases.

CONCLUSION
Mushroom poisonings in Bulgaria have a high frequency and are responsible for 10.7% of hospitalizations due to acute intoxication.They affect to the same extent both sexes.The majority of patients (62.6%) were the age group from 25 to 60 years.Mushroom intoxications are typical of late spring, summer and autumn, with a peak in October.Mushroom poisoning causing irritant gastroenterocolitis and those with Amanita pantherina and Amanita muscaria have a good prognosis.Amanita phalloides intoxications are characterized by the development of life-threatening organ damages and high lethality.They account for 11.4% of lethality in acute intoxications.