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Wild Mushroom Poisoning in North India: Case Series with Review of Literature

2014; Elsevier BV; Volume: 4; Issue: 4 Linguagem: Inglês

10.1016/j.jceh.2014.09.004

2213-3453

Nipun Verma, Ashish Bhalla, Susheel Kumar, Radha K. Dhiman, Yogesh Chawla,

Plant Toxicity and Pharmacological Properties

Mushroom is an important constituent of diet in many ethnic tribes in India. Ethnic Indian tribes are known to consume nearly 283 species of wild mushrooms out of 2000 species recorded world over. Although they are experts in distinguishing the poisonous from edible mushrooms, yet occasional cases of toxicity are reported due to accidental consumption of poisonous mushrooms. We report amanita like toxicity in a family after consumption of wild mushrooms resulting in fatal outcome. Mushroom is an important constituent of diet in many ethnic tribes in India. Ethnic Indian tribes are known to consume nearly 283 species of wild mushrooms out of 2000 species recorded world over. Although they are experts in distinguishing the poisonous from edible mushrooms, yet occasional cases of toxicity are reported due to accidental consumption of poisonous mushrooms. We report amanita like toxicity in a family after consumption of wild mushrooms resulting in fatal outcome. Mushroom poisoning (aka mycetism) in humans has been described since time immemorial, which has been witnessed by ancient writings like "Rigveda" (at least 3500 B.C.) and "Atharvaveda" (at least 1500 B. C.) The first written record about a fungus is the death from fungal poisoning, of a mother, daughter and two full grown sons, an event, which Euripides (456–450 B.C.) commemorated by an epigram.1Jha S.K. Tripathi N.N. Recent scenario in diversity, distribution and applied value of macrofungi: a review.Int J Univ Pharm Life Sci. 2012; 2: 102-125Google Scholar In India, Mushroom has been a source of diet and article of commerce since long time and across many cultures. Poisoning results from unintentional consumption of poisonous wild mushrooms. The cases however remain undiagnosed, underreported and unpublished. A large number of suspected cases are reported in lay press. There have been small epidemics of mushroom poisoning culminating in mortality especially during monsoon. The published literature from India is sparse and mostly in the form of case reports.2Deshmukh S.K. Natarajan K. Verekar S.A. Poisonous and hallucinogenic mushrooms of India.Int J Med Mushr. 2006; 8: 251-262Crossref Scopus (6) Google Scholar, 3Natarajan K. Kaviyarasan V. Chlorophyllum molybdites poisoning in India – a case study.Mycologist. 1991; 5: 70-71Crossref Scopus (7) Google Scholar, 4George P. Hegde N. Muscarinic toxicity among family members after consumption of mushrooms.Toxicol Int. 2013; 20: 113-115Crossref PubMed Scopus (8) Google Scholar The present case report depicts one such incident of accidental death of three members of a family, owing to consumption of wild mushrooms. A family consisting of 35 yr old man, 33 yr old lady (mother), 14 yr old daughter and 13 yr old son residents of a village Trela, district Mandi, Himachal Pradesh, India consumed wild mushrooms harvested from mountains in September 2011. Subsequently all four of them developed pain abdomen, vomiting and bloody diarrhea 4–6 h after consumption. They were taken to community health center where intravenous (IV) fluids and anti-emetics were given and diarrhea and vomiting settled after 24–36 h and they remained relatively asymptomatic for 8–10 h. This was followed by progressive altered sensorium and behavior and irritability for which referred to district hospital Mandi, where found to have transaminitis >10 times elevated and jaundice. Provisional diagnosis of toxic hepatitis secondary to poisonous wild mushrooms was made. Patients were managed with IV fluids, antibiotics, anti-emetics and antacids. The man died on day 4 of the illness and in view of worsening sensorium the remaining three patients were referred to our center, a tertiary care hospital in North India. All the patients had similar complaints of jaundice and altered sensorium at admission. On Examination all three were afebrile, tachypneic (respiratory rate 26–32/min), had tachycardia (respiratory rate 120–160/min) with normal blood pressures at presentation. Mother was pale with deep icterus, grade 3 hepatic encephalopathy, brisk deep tendon reflexes and down going planters. Investigations revealed anemia ((hemoglobin 7.6 g/dL), leukocytosis [total leukocyte counts (TLC) 16,000/mm3], conjugated hyperbilirubinemia (total bilirubin/conjugated bilirubin 5.7/4.6 mg/dl), coagulopathy (prothrombin time >2 min), transaminitis [aspartate aminotransferase (AST)/alanine aminotransferase (ALT) 1580/2400 IU/ml)], deranged renal function test (creatinine 2.8 mg/dL) and hyperkalemia (K+ 5.6 mEq/L) with tall 'T' waves in electrocardiogram (ECG). Ultrasound abdomen showed fatty liver, liver span 13.4 cm, gall bladder wall thickening with pericholecystic fluid, bilateral renal parenchymal disease and mild ascites (Table 1).Table 1Patient Characteristics.ParametersPatient 1: motherPatient 2: sonPatient 3: daughterResidenceRural, hillsRural, hillsRural, hillsType of mushroom consumedWildWildWildOnset of symptoms after consumption4 h4–5 h6 hInitial symptomsPain abdomen, vomitings, bloody diarrheaPain abdomen, vomitings, bloody diarrheaPain abdomen, vomitings, bloody diarrheaResolution of initial symptoms24–28 h28–30 h30–36 hPeriod of convalescence8–10 h8–10 h8–10 hProgression of symptomsJaundice, altered sensoriumJaundice, altered sensoriumJaundice, altered sensoriumDay of admission to ICU4th4th5thGeneral examination findingsPallor, icterusPallor, icterusIcterusCNS examinationGrade 3 hepatic encephalopathyGrade 3–4 hepatic encephalopathyGrade 3 hepatic encephalopathyHyperreflexiaArreflexiaHyperreflexiaPlanters down goingPlanters mutePlanters down goingNormal toneHypertoniaNormal toneInvestigations: Hemoglobin7.6 g/dl10.7 g/dl12.1 g/dlLeukocyte count16000/mm35000/mm39200/mm3AST/ALT1580/2400 U/L2814/3759 U/L573/1463 U/LBilirubin total/conjugated5.7/4.6 mg/dl5.2/3.1 mg/dl5.2/3.6 mg/dlProthrombin time>2 min>2 min>2 minSerum sodium125 meq/L135 meq/L137 meq/LSerum creatinine2.8 mg/dl0.5 mg/dl3.0 mg/dlArterial gasesMetabolic acidosisMetabolic acidosisMetabolic acidosisUrine routineNormalNormalNormalUSG abdomenRaised liver echogenicity, 13.4 cm GB wall thickening, pericholecystic fluid, bilateral renal parenchymal disease, ascitesRaised liver echogenicity, 12.4 cm No ascitesRaised liver echogenicity, 11.5 cm GB wall thickening, pericholecystic fluid, bilateral renal parenchymal disease, ascites, bilateral mild pleural effusionManagementICU based including penicillin and silibininICU based including penicillin and silibininICU based including penicillin and silibininCourseDICPresentPresentPresentOnset of hypotension10 h20 h24 hDemise12 h24 h60 hTerminal eventsRefractory shock, MODS, sinus bradycardiaRefractory shock, MODSRefractory shock, MODS, ventricular fibrillation, seizures Open table in a new tab Son had pallor, icterus, grade 3–4 hepatic encephalopathy, generalized hypertonia, absent deep tendon reflexes and mute planters. Investigations revealed anemia (hemoglobin 10.7 g/dL), normal leukocyte count, conjugated hyperbilirubinemia (total bilirubin/conjugated bilirubin 5.2/3.1 mg/dL), coagulopathy (prothrombin time > 2 min), transaminitis (AST/ALT 2814/3759 IU/ml), normal renal function test, electrolytes and ECG. Ultrasound abdomen showed fatty liver; span 12.4 cm and no free fluid. Noncontrast computed tomography (NCCT) head showed cerebral edema (Table 1). Daughter had icterus, no pallor, grade 3 hepatic encephalopathy, brisk deep tendon reflexes and down going planters. Investigation revealed hemoglobin 12.1 g/dL, TLC 9200/mm3, conjugated hyperbilirubinemia (total bilirubin/conjugated bilirubin 5.2/3.6 mg/dl), coagulopathy (prothrombin time >2 min), transaminitis (AST/ALT: 573/1463 IU/ml), normal Renal function test, electrolytes and ECG. Ultrasound abdomen showed fatty liver, liver span 11.5 cm, Gall bladder wall thickening with pericholecystic fluid, bilateral renal parenchymal disease, mild ascites and mild bilateral pleural effusion. NCCT head showed cerebral edema (Table 1). All three were managed in the liver ICU using standard protocol for treatment for acute liver failure including intensive monitoring, intubation for airway protection, IV fluids, IV broad spectrum antibiotics, IV mannitol, elevation of head end, hyperventilation, appropriate sedation, IV proton pump inhibitors, Inj vitamin K, Inj dextrose, vasopressor support and intensive monitoring and management of electrolytes imbalances and blood sugars. Inj penicillin G @1 million units/kg/d and silibinin @ 30 mg/kg/day were also given. Gastric aspirate from all three patients showed active upper gastrointestinal bleed, which was managed with fresh frozen plasma and packed red blood cell transfusions. Mother developed hypotension requiring increasing doses of vasopressors with falling urine output and had progressive sinus bradycardia. She sustained cardiac arrest after about 12 h of ICU admission and could not be revived. After about 20 h of ICU admission, the son developed worsening sensorium, falling urine output and hypotension requiring increasing vasopressor support. He was managed conservatively with fluids and blood products, however his condition kept on worsening. He sustained cardiac arrest after about 24 h of stay and could not be revived. Daughter developed hypotension requiring vasopressors and seizures after 24 h of stay which responded to Inj levetiracetam. About 48 h of stay she had cardiac arrest following ventricular fibrillation and was revived in 10 min but her condition kept on deteriorating. She sustained another cardiac arrest after about 60 h of stay and could not be revived. Post mortem liver biopsy from mother's liver showed features of cholestasis and autolytic changes. Liver biopsy from the son and daughter, revealed confluent areas of hepatic necrosis with few surviving hepatocytes showing intracytoplasmic cholestasis, features suggestive of fulminant hepatic damage. Mushrooms are the fleshy, spore-bearing fruiting body of higher fungi, typically produced above ground on soil or on their food source. Traditional mycological knowledge of most Indian ethnic groups is known to be extensive and profound, Ethnic Indian tribes are known to consume nearly 283 species of wild mushrooms out of 2000 species recorded world over.5Purkayastha R.P. Chandra A. Manual of Indian Edible Mushrooms. Jagendra Book Agency, New Delhi, India1985Google Scholar Around 100 species of mushrooms in India are known to be poisonous to humans,6Diaz J.H. Syndromic diagnosis and management of confirmed mushroom poisonings.Crit Care Med. 2005; 33: 427-436Crossref PubMed Scopus (117) Google Scholar hepatotoxicity is caused mainly by amatoxin and gyromitrin synthesized by a number of Amanita species and some members of the Galerina, Lepiota, and Conocybe genera.7Karlson-Stiber C. Persson H. Cytotoxic fungi—an overview.Toxicon. 2003; 42: 339-349Crossref PubMed Scopus (203) Google Scholar, 8Enjalbert F. Rapior S. Nouguier-Soulé J. Guillon S. Amouroux N. Cabot C. Treatment of amatoxin poisoning: 20 year retrospective analysis.J Toxicol Clin Toxicol. 2002; 40: 715-757Crossref PubMed Scopus (292) Google Scholar Common poisonous mushroom species identified from Hills in South India are Omphalotus olivascens, Mycena pura and Chlorophyllum molybdites but human poisonings are uncommon as ethnic tribes are experienced in identifying poisonous from non poisonous mushrooms.5Purkayastha R.P. Chandra A. Manual of Indian Edible Mushrooms. Jagendra Book Agency, New Delhi, India1985Google Scholar, 9Kumar M. Kaviyarasan V. Few common poisonous mushrooms of Kolli hills, south India.J Acad Indus. Res. 2012; 1: 19-22Google Scholar, 10Sarma T.C. Sarma I. Patiri B.N. Wild edible mushrooms used by some ethnic tribe in western Assam.Bioscan. 2010; 3: 613-625Google Scholar Previous case series from India include one which had fifteen cases of Amanita phalloides poisoning11Sharma S.K. Aggarwal A. Pal L.S. et al.Mushroom (Amanita phalloides) poisoning with special reference to serum enzyme levels.J Indian Med Assoc. 1980; 75: 213-217PubMed Google Scholar with major clinical presentation with nausea, vomiting, diarrhea, jaundice and hepatic or renal failure after 48 h, or both. The early rise in serum AST/ALT levels was associated with high mortality. Study from the same institution has previously described prevalence of mushroom poisoning in children to be 3.2% out of all accidental poisonings.12Singh S. Singhi S. Sood N.K. et al.Changing pattern of childhood poisoning (1970–1989): experience of a large north Indian hospital.Indian Pediatr. 1995; 32: 331-336PubMed Google Scholar In our series acute liver failure and MODS resulted in fatality in all the three family members, after consumption of wild mushrooms harvested from hills of Himachal Pradesh. The species identification and toxin analysis could not be performed due to non-availability of mushroom specimen; however, the clinical presentation was similar to amanita poisoning. Amanita toxicity is characterized by an asymptomatic incubation period followed by the gastrointestinal and hepatotoxic phases, leading eventually to multi-organ failure and death (Table 2). This is probably the first reports of wild mushroom poisoning from Himachal Pradesh. In the absence of mushroom for species identification, syndromic approach to diagnosis and management is essential.6Diaz J.H. Syndromic diagnosis and management of confirmed mushroom poisonings.Crit Care Med. 2005; 33: 427-436Crossref PubMed Scopus (117) Google Scholar Similar case series from Assam has emphasized high mortality in patients aged less than 10 (83%) or more than 50 yr (100%) and major cause being acute liver failure and acute renal failure.13Dutta A. Kalita B.C. Pegu A.K. A study of clinical profile and treatment outcome of mushroom poisoning – a hospital based study.Assam J Int Med. 2013; 3: 13-17Google ScholarTable 2Clinical Phases of Amatoxin Poisoning.PhasesOnset from ingestionSymptoms and signsStage 1.Lag phase 0–24 hAsymptomaticStage 2.Gastrointestinal phase 6–24 hNausea, vomiting, crampy abdominal pain, and severe secretory diarrheaStage 3.Apparent convalescence 24–72 hAsymptomatic, worsening of hepatic and renal function indicesStage 4.Acute liver failure 4–9 daysHepatic and renal failure → multi-organ failure → death Open table in a new tab C. molybdites poisoning also presents with gastrointestinal manifestations but colicky abdominal pain and explosive, bloody diarrhea are characteristic features.3Natarajan K. Kaviyarasan V. Chlorophyllum molybdites poisoning in India – a case study.Mycologist. 1991; 5: 70-71Crossref Scopus (7) Google Scholar Toxicity due to Clitocybe species of mushrooms results in muscarinic symptoms.4George P. Hegde N. Muscarinic toxicity among family members after consumption of mushrooms.Toxicol Int. 2013; 20: 113-115Crossref PubMed Scopus (8) Google Scholar The toxicity of A. phalloides is related to two distinct groups of toxins: phallotoxins and amatoxins. The phallotoxins are toxic to cell membrane of enterocytes leading to initial diarrhea like illness whereas amatoxins (α-amanitin and β-amanitin) are responsible for the toxic effect leading to acute liver failure, renal failure and potential toxicities to pancreas, adrenal glands, and testes.14Koppel C. Clinical symptomatology and management of mushroom poisoning.Toxicon. 1993; 31: 1513-1540Crossref PubMed Scopus (102) Google Scholar, 15Derenzini M. Betts C.M. Busi C. et al.Ultrastructural changes in beta-cells of pancreatic islets in alpha-amanitin-poisoned mice.Virchows Arch B Cell Pathol. 1978; 28: 13-20PubMed Google Scholar Amanitins act via inhibiting eukaryotic RNA polymerase-II and thus interrupting transcription in humans resulting in decreased mRNA and protein synthesis and leading eventually to cell death. Since these toxins are not destroyed by cooking, the toxicity may occur after eating the cooked mushrooms. There is some evidence suggesting that parboiling can attenuate their toxicity but it has not being conclusively proven in studies. Classically, Clinical manifestations occur in four stages as described in Table 2. Diagnosis is based on careful assessment of history, circumstantial evidence linking ingestion of mushroom to onset of symptoms. The identification by an experienced mycologist of the remaining mushrooms can be crucial for diagnosis. In the absence of these, the diagnosis is largely clinical and can best be probable.6Diaz J.H. Syndromic diagnosis and management of confirmed mushroom poisonings.Crit Care Med. 2005; 33: 427-436Crossref PubMed Scopus (117) Google Scholar, 7Karlson-Stiber C. Persson H. Cytotoxic fungi—an overview.Toxicon. 2003; 42: 339-349Crossref PubMed Scopus (203) Google Scholar Since no specific antidote to amatoxins is currently available, management is largely supportive. Severe acute liver failure is a grade I indication for liver transplantation. Supportive measures including correcting dehydration, electrolyte abnormalities, and metabolic acidosis caused by the gastrointestinal phase of the intoxication remain the cornerstone.6Diaz J.H. Syndromic diagnosis and management of confirmed mushroom poisonings.Crit Care Med. 2005; 33: 427-436Crossref PubMed Scopus (117) Google Scholar The specific treatments consist of detoxification procedures including gastric lavage, multidose activated charcoal and extracorporeal purification using Molecular Adsorbent Recirculating System (MARS).16Mitzner S.R. Stange J. Klammt S. et al.Extracorporeal detoxification using the molecular adsorbent recirculating system for critically ill patients with liver failure.J Am Soc Nephrol. 2001; 12: S75-S82PubMed Google Scholar, 17Faybik P. Hetz H. Baker A. et al.Extracorporeal albumin dialysis in patients with Amanita phalloides poisoning.Liver Int. 2003; 23: 28-33Crossref PubMed Scopus (38) Google Scholar Other supportive drugs include Silibinin, Penicillin G and free radical scavenger like N-acetylcysteine. Silibinin is a silymarin derivative and acts via competing with amatoxins for trans-membrane transport and inhibits the penetration of amanitin into hepatocytes, thus having direct hepatoprotective effect. Recommended dose is 20–50 mg/kg/day intravenously for 48–96 h or oral dose from 1.4 to 4.2 g/d.18Faulstich H. Jahn W. Wieland T. Silybin inhibition of amatoxin uptake in the perfused rat liver.Arzneimittelforschung. 1980; 30: 452-454PubMed Google Scholar, 19Sorodoc L. Lionte C. Sorodoc V. et al.Is MARS system enough for A. phalloides-induced liver failure treatment?.Hum Exp Toxicol. 2010; 29: 823-832Crossref PubMed Scopus (25) Google Scholar Penicillin G have a similar mechanism of action, displacing amanitin from the binding to plasma protein and thus promoting its excretion and preventing its hepatic uptake. It is recommended to administer it in continuous intravenous form as Na/K penicillin G (1,000,000 IU/kg for the first day, then 500,000 IU/kg for the next two days).18Faulstich H. Jahn W. Wieland T. Silybin inhibition of amatoxin uptake in the perfused rat liver.Arzneimittelforschung. 1980; 30: 452-454PubMed Google Scholar, 19Sorodoc L. Lionte C. Sorodoc V. et al.Is MARS system enough for A. phalloides-induced liver failure treatment?.Hum Exp Toxicol. 2010; 29: 823-832Crossref PubMed Scopus (25) Google Scholar Early empiric administration may be beneficial. There is also some data suggesting hepatoprotection by N-acetylcysteine (NAC), in the management of amatoxin intoxication.20Sklar G.E. Subramaniam M. Acetylcysteine treatment for non-acetaminophen-induced acute liver failure.Ann Pharmacother. 2004; 38: 498-500Crossref PubMed Scopus (50) Google Scholar All three specific measures were utilized in our patients but the outcome was not favorable. Despite these measures the mortality with A. phalloides poisoning ranges from 10 to 20%.18Faulstich H. Jahn W. Wieland T. Silybin inhibition of amatoxin uptake in the perfused rat liver.Arzneimittelforschung. 1980; 30: 452-454PubMed Google Scholar, 19Sorodoc L. Lionte C. Sorodoc V. et al.Is MARS system enough for A. phalloides-induced liver failure treatment?.Hum Exp Toxicol. 2010; 29: 823-832Crossref PubMed Scopus (25) Google Scholar In present case report, the appropriate ICU care and specific measures like penicillin G, silibilin and N-acetylcysteine were instituted with a delay of 96–120 h after the onset of symptoms and all three had poor prognostic criteria i.e. grade III–IV encephalopathy, grossly deranged Coagulogram and mushroom being an etiology, hence mortality was high (100%). Similar case report of three family members affected with mushroom toxicity and with similar clinical profile resulting in death of one in whom specific therapy was not instituted was reported from India in 2003. The remaining two who were fortunate to receive Inj. penicillin and silibinin survived.21Garg M.S. Mushroom poisoning.MJAFI. 2003; 59: 266-268Google Scholar Liver transplantation has been described to improve mortality in amatoxin-induced acute liver failure in selected patients and before development of grade 4 hepatic encephalopathy.22Passo B. Harrison D.C. A new look at an old problem: mushroom poisoning.Am J Med. 1975; 58: 505-509Abstract Full Text PDF PubMed Scopus (37) Google Scholar, 23Teutsch C. Brennan R.W. Amanita poisoning with recovery from coma: a case report.Ann Neurol. 1978; 3: 177-179Crossref PubMed Scopus (18) Google Scholar Ganzert et al24Ganzert M. Felgenhauer N. Zilker T. Indication of liver transplantation following amatoxin intoxication.J Hepatol. 2005; 42: 202-209Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar retrospectively analyzed the outcome of a large series of amatoxin intoxication cases and found that predictors of death were the prothrombin index in combination with the serum creatinine level on 3–10 days after ingestion. Overall, the prognosis of amanitin-induced acute liver failure remains quite poor.22Passo B. Harrison D.C. A new look at an old problem: mushroom poisoning.Am J Med. 1975; 58: 505-509Abstract Full Text PDF PubMed Scopus (37) Google Scholar, 23Teutsch C. Brennan R.W. Amanita poisoning with recovery from coma: a case report.Ann Neurol. 1978; 3: 177-179Crossref PubMed Scopus (18) Google Scholar In conclusion, amanita toxicity should be considered in the differential diagnosis of acute gastroenteritis and renal failure, especially during monsoon season in populations known for consuming wild mushroom. There is a need to educate the masses to recognize these poisonous mushrooms. In the absence of the culprit fungus and diagnostic tests, definitive diagnosis may be difficult. Management is focused on prompt recognition of the toxidrome, early hospitalization, gastric lavage, hydration, penicillin and silymarin therapy with hepatorenal support and the delay in treatment can result in nearly 100% mortality. Regional reference laboratories should be equipped for testing serum levels of amanitin levels to confirm the diagnosis. All authors have none to declare.