Poisoning by Amatoxin-Containing mushrooms in suburban New York Report of four cases

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  • CLINICAL TOXICOLOGY, 32(6), 715-72 1 (1994)

    CASE REPORTS

    POISONING BY AMATOXIN-CONTAINING MUSHROOMS IN SUBURBAN NEW YORK - REPORT OF FOUR CASES

    Donald A. Feinfeld, M.D.*,**; Howard C. Mofenson, M.D.**,***; Thomas Caraccio, Pharm.D.***; Mitsu Kee, B.S.**

    Department of Medicine, Nassau County Medical Center, East Meadow, New York*; Long Island Regional Poison Control Center,

    Mineola, New York**; State University of New York Health Sciences Center at Stony Brook, Stony Brook, New York***

    ABSTRACT

    We report four cases of poisoning with amatoxin-producing mushrooms in suburban Long Island. All occurred when amateur mushroom hunters picked mushrooms from neighboring lawns. Two patients presented 30 hours post ingestion with evidence of acute hepatic dysfunction. One survived, after treatment with charcoal and penicillin; the other, a 90-year-old woman with prior cardiac disease soon developed shock and subsequently died. The other two patients were admitted 18 hours after ingestion of Lepiotu chlorophyllwn and received prompt charcoal hemoperfusion. Both did well, although one had a mild elevation of transaminases. Although most reports of amatoxin poisoning originate in Europe, these cases confirm that amatoxin-producing mushrooms, including Lepiora chZorophyZZwn, may be found in northeastern American suburbs. Such patients who present prior to 24 hours after ingestion should receive charcoal hemoperfusion if a lethal dose (> 50 g of mushroom) has been eaten. (Key Words: amatoxin; hepatotoxicity; hernoperfhion; mushrooms.)

    Address reprint requests to: Dr. Donald A. Feinfeld, Department of Medicine, Nassau County Medical Center, 2201 Hempstead Turnpike, East Meadow, NY 11554.

    7 15

    Copyright 1994 by Marcel Dekker, Inc.

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  • 716

    INTRODUCTION

    FEINFELD ET AL.

    Although reports of poisoning by cyclopeptide-producing mushrooms of the Amanita/GcrlerinaLepiota group are not unknown in the US, particularly in the West (1,2), the majority of reports of this intoxication come from central Europe, where amateur mushroom-hunting is common. Since most physicians in the US do not often see this problem, it is useful to review the clinical course of amatoxin poisoning, along with current recommendations for management. In this paper, we report four cases, one of them fatal, that occurred in Long Island suburbs of New York City over a two-year period.

    Case Reports

    Patient 1 was a 90-year-old woman with a past history of hypertension and recent onset of complete heart block, treated with a permanent pacemaker. Her medications were enalapril and 1 aspirin tablet daily. One evening she ate several wild mushrooms which she had picked in a neighbor's yard (unfortunately, she was unable to tell the exact number). The mushrooms were described as white, with a large base and no ring around the stalk. After 12 h she began to have diarrhea, weakness, nausea, and vomiting. Twenty-four hours after the ingestion she called Long Island Regional Poison Control Center and was told to go immediately to a hospital. She came to Nassau County Medical Center 30 h after the ingestion and was found to have blood pressure 150/80 mm/Hg, pulse 75 bpm and regular, respirations 18 bpm, and normal temperature. Physical examination, other than the presence of the pacemaker, was unremarkable. Laboratory values included serum K+ 2.5 mEq/L, blood glucose 11.2 mmol/L (202 mg/dL), urea nitrogen 16.1 mmol/L (45 mg/dL), creatinine 124 pmol/L (1.4 mg/dL), Ca 2.5 mmol/L (10.4 mg/dL), bilirubin 10.3 pmol/L (0.6 mg/dL), aspartate animotransferase (AST) 247 U/L, alanine aminotransferase (ALT) 149 U/L (Table l), prothrombin time (FT) 13.6 sec (1.1 sec elevated), and partial thromboplastin time 0 25.9 sec.

    Hospital management included intravenous hydration, penicillin 300,000 U/d, cimetidine, activated charcoal by nasogastric tube, and intramuscular vitamin K. However, the patient quickly developed hypotension refractory to pressors, along with fulminant hepatic failure. By hospital day 3 AST was 1833 U/L and ALT 1897 U/L, while PT had risen to 29.6 sec and P'IT to 52.4 sec. On day 4 she developed respiratory distress and required intubation. Lactic acidosis ensued, and the patient expired on hospital day 5 , with continually rising liver function tests. Post-mortem examination showed right pleural eflbsion, pericardial effusion, ascites, left ventricular hypertrophy, coronary atherosclerosis, and hepatic necrosis. Toxicologic analysis of admission and post-mortem serum specimens identified amatoxins.

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  • MUSHROOM POISONING 717

    TABLE 1

    Patients Treated for Amanita/Lepiota Mushroom Poisoning

    Days to Peak Underlying Peak AST/ALT

    Pt Age Sex Conditions AST/ALT (UL) 1 90 F HeartBlock 7 died 409915394

    2 64 M Thyroiditis 5 562018620 Hypertension

    3 40 F None 6 104197

    4 42 M None 2 20124

    Treatment Charcoal oral Penicillin Charcoal oral Penicillin Charcoal oral Hemoperfusion Penicillin Charcoal Hemoper fusion Penicillin

    Outcome Died of Hepatic failure Survived, Hepatitis survived, Mild elevation of ASTIALT Survived, No abnormal tests

    Patient 2 was the 64-year-old son of Patient 1. His only past medical illness was Hashimotos thyroiditis, for which he was taking levothyroxine. He ate the same mushrooms at the same time as his mother and developed similar nausea, vomiting, and cramps 12 h post ingestion. He only came to the hospital, along with Patient 1, 30 h post ingestion.

    Physical examination was entirely unremarkable on admission to intensive care. Blood chemistries included glucose 15.3 mmol/L (277 mg/dL), urea nitrogen 11.8 mmol/L (33 mg/dL), creatinine 159 pmol/L (1.8 mg/dL), bilirubin 15.4 pmol/L (0.9 mg/dL), AST 174 U/L, ALT 180 U/L (Table l), alkaline phosphatase 105 U/L, PT 14.5 (2 sec elevated), and PTT 31.4 sec.

    Hospital management was similar, including intravenous hydration, penicillin 300,000 U/d, cimetidine, oral charcoal, and intramuscular vitamin K. During the next 48 h there was a progressive rise in serum transaminase levels, with AST peaking at 5620 U/L and ALT at 8620 U/L. The bilirubin rose to 109 pmol/L (6.4 mg/dL) on hospital day 5 , but serum alkaline phosphatase remained within normal limits. The PT reached a maximum of 23.3 sec on hospital day 3. All laboratory values gradually returned to normal; the course was complicated only by C. diflcile colitis. Stool examinations for other pathogenic bacteria, parasites, and leukocytes were negative. The patient was discharged, asymptomatic, after one month.

    Patient 3 was a 40-year-old woman, part-time roofer, whose only past medical history was having had a hysterectomy for leiomyomata. One evening she gathered mushrooms from a neighbors lawn, having just purchased a book on mushroom hunting. The mushrooms were described as white, with a large

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  • 718 FEINFELD ET AL.

    base and no ring, and they were mistaken for shaggy manes (Cbprinus cornatus). The patient fried them and served them to herself and her husband for dinner, each eating 4 to 6 mushrooms. Three hours later the patient developed severe nausea and vomited 8-10 times, expelling a few of the mushroom fragments. This was followed by explosive diarrhea, with 30 stools over the next 8 h. She was admitted to a local hospital by her private physician and treated with intravenous fluids and prochlorperazine. However, when the county mycologist identified the mushrooms as belonging to the AmanituL.epiotu group, she was transferred to Nassau County Medical Center for more intensive treatment. The patient had no physical findings except for mild pallor. Initial laboratory tests showed normal blood chemistries, mild anemia (hematocrit 32%), bilirubin 11.9 pmol/L (0.7 mg/dL), AST 44 U/L, ALT 60 U/L (Table l), alkaline phosphatase 44 U/L, PT 11.9 sec. Serological tests for hepatitis A, B, and C were uniformly negative.

    Upon arrival 18 h post ingestion, the patient was begun on oral charcoal, intravenous fluids, and penicillin 300,000 U/d. Twenty hours post ingestion a 3 h charcoal hemoperfusion was performed. The procedure required administration of 20,000 units of heparin and was followed by elevation of the partial thromboplastin time for 12 h and a fall in platelet count from 202,000/mm3 to 76,000/mm3. However, by 24 h after the procedure, the prothrombin time was 12.5 sec and the platelet count 1 16,000/mm3.

    The patient felt better after 48 h and had no further systemic symptoms except for occasional headaches. By hospital day 3 the ALT had fallen to 46. However, on hospital day 6 AST rose to 98 and ALT to 97 U/L. By the following day, eight days after the mushroom ingestion, AST was 104 and ALT 95 U L . Subsequently there was a gradual fall in transaminase levels, and the patient was discharged, asymptomatic, on day 10. Final review of the mushroom fragments by the county mycologist identified them as Lepiotu chlorophyllwn.

    Patient 4 was the husband of patient 3, who ingested 4 to 6 of the same mushrooms. Three hours later he noted copious vomiting and regurgitated many mushroom fragments. He also noted profuse diarrhea, with 30 stools, and also arrived 18 h post ingestion. Physical examination was entirely normal, and all laboratory tests were within normal limits.

    Like Patient 3, because of the identification of the mushrooms as AmunituLLepiotu, this patient received charcoal by mouth, intravenous fluids and penicillin, and was given a charcoal hemoperfusion 20 h post ingestion. He tolerated the procedure well, without complications. He remained asymptomatic; laboratory tests remained normal throughout his hospitalization (Table l), and he was discharged home on the sixth day.

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  • MUSHROOM POISONING 719

    DISCUSSION

    Poisoning with amatoxin-producing mushrooms is uncommon in North America, although it is by no means rare (3). However, most reported cases originate in Europe, particularly the central and eastern countries. A literature search found 46 reports of poisoning with cyclopeptide mushrooms during the past 5 years of which 36 (78%) originated in Europe, with 24 (52%) from Eastern and central Europe. Only two reports came from the US, one from the far West and one from New Jersey. However, as the above cases indicate, these mushrooms can be found anywhere, including the suburbs of New York City.

    The usual course of amatoxin-containing mushroom poisoning is felt to be explosive vomiting and diarrhea, beginning about 3-12 h after the ingestion (43). The mortality is usually due to hepatic failure, which begins 3 to 4 days after ingestion (6). However, as seen in Table 2, three of the four patients had at least some initial elevation of serum transaminase 18-30 h after the reported ingestion. In cases 1 and 2, this went on to a full-blown toxic hepatitis, with one fatality probably mediated by the patients advanced age and underlying cardiac disease.

    In patient 3 the ALT, initially 60 U/L, fell to 46 U/L by day 3, only to rise again to 97 U/L on day 5, accompanied by a rise in her initially normal AST to 104 U/L. The initial elevation of transaminase levels in 3 of the 4 patients is consistent with reports that hepatotoxicity from cyclopeptides may begin early after ingestion (1,2,4,5). Patient 4, unlike his wife (patient 3), suffered no evident hepatotoxicity, probably due to his having vomited up a larger fraction of the mushrooms he had ingested, along with his much greater size (height 190.5 cm, weight 125 kg).

    Cases 3 and 4 in our series appear to be one of the rare incidences of poisoning with Lepioru mushrooms in the US. The extremely short latency of 3 h between ingestion and symptoms is not typical of amatoxin but the mushrooms were identified by the County mycologist on examination of both the regurgitated fragments and some uneaten mushrooms. Samples of urine and pre- and post-hemoperfusion serum sent to the medical examiners laboratory were, unfortunately, discarded. A review of poisoning from cyclopeptide-producing mushrooms since 1981 disclosed only one case involving Ltpioru (2). The only report in the world literature of Lepioru intoxication in the past decade originated in Turkey (7). In that series, 14 of 27 patients died.

    The decision to perform charcoal hemoperfusion on patients 3 and 4 but not patients 1 and 2 was based on a recent review of the literature about extracorporeal removal of ingested toxins (8). Although hemodialysis or hemoperfusion is routinely performed in cases of poisoning with volatile

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  • 720 FEINFELD ET AL.

    TABLE 2

    Patients Treated for Ama&/Lepiota Mushroom Poisoning

    Delay Before Initial Peak Days to Patient Presentation Q ASTIALT (UIL) ASTIALT (UIL) Peak ASTlALT

    1 30 247( t )/149( t ) 4099/5394 7 (died) 2 30 174( t )/180( t ) 5620/8620 5 3 18 44/60( t ) 104/97 6 4 18 15/18 20/24 2

    t = Elevated

    alcohols, lithium, and long-acting theophylline preparations, it is not usually recommended for mushroom poisoning. However, Wauters et al. (9) reported 8 patients poisoned with Amanitu phalloides who began hemoperfusion within 24 h after the ingestion. Although some of these patients had elevated transaminase levels, there were no fatalities. A recent series from Slovakia (10) confirms that the effectiveness of hemoperfusion in amatoxin poisoning depends largely on initiation of treatment prior to 24 h after the ingestion. Since patients 3 and 4 had ingested a potentially fatal amount of mushroom (> 50 g), it was decided that they should be hemoperfused. Clinically, however, they were not at high risk. Patients 1 and 2 were not hemoperfused because they presented more than 24 h after eating the mushrooms and had additional complicating factors. Patient 1 was hypotensive, which precludes effective hemoperfusion, and patient 2 already had abnormal clotting (elevated PT and PIT). Since the major complication of hemoperfusion is thrombocytopenia, it was felt that the risk of bleeding outweighed the doubtful benefit of a late treatment. (Parenthetically, these patients were erroneously given vitamin K intramuscularly; due to the bleeding diathesis, it should be given orally or intravenously.) Amatoxins usually disappear rapidly from the plasma after 24 h and are bound in tissue, particularly in the kidneys (11,12). A study in the dog (11) shows amatoxin is picked up in the liver within 5 h of IV administration. In th...