Christine Rauber-Lüthy

Mushroom poisoning: A study on circumstances of exposure and patterns of toxicity

BACKGROUND Picking wild mushrooms is a popular pastime in Switzerland. Correct identification of the species is difficult for laypersons. Ingestion of toxic mushrooms may result in serious toxicity, including death. The aim of the study is to analyze and describe the circumstances of exposure to mushrooms, and to define the clinical relevance of mushroom poisoning for humans in Central Europe. MATERIALS AND METHODS We performed a retrospective case study and analyzed all inquiries concerning human exposures to mushrooms (n = 5638, 1.2% of all inquiries) which were reported to the Swiss Toxicological Information Centre between January 1995 and December 2009. RESULTS The most frequent reason for contacting the poison center in cases of adult exposure was toxicity resulting from edible species. Pediatric exposure predominantly occurred from mushrooms found around the home. Severe symptoms have not only been observed after ingestion of non-amatoxin-containing toxic mushrooms, i.e. Boletus sp. and Cortinarius sp., but also after meals of edible species. The mortality of confirmed amatoxin poisonings was high (5/32) compared to other reports. CONCLUSIONS Inquiries regarding mushroom poisoning were a relatively infrequent reason for contacting the poison center. Nevertheless, accidental ingestion of toxic mushrooms can be responsible for severe or fatal poisonings. Although pediatric exposure to mushrooms found around the home has not led to serious toxicity in this study, prevention of exposure is warranted. Inspection of wild mushrooms by a certified mushroom expert or a mycologist seems to be a safe procedure which should be recommended.

Escitalopram causes fewer seizures in human overdose than citalopram.

Context. Seizures are a recognized complication of acute overdose with the racemic (1:1 ratio of R- and S-enantiomers) selective serotonin reuptake inhibitor antidepressant citalopram. Objective. We tested the hypothesis that escitalopram (the therapeutically active S‐enantiomer of citalopram) causes fewer seizures in overdose than citalopram at comparable doses of the S-enantiomer. Methods. Multicenter retrospective review of cases with citalopram and escitalopram overdose reported to German, Austrian, and Swiss Poisons Centers between 1997 and 2006. Results. 316 citalopram and 63 escitalopram cases were analyzed. Somnolence, nausea, vomiting, tachycardia, QT prolongation, and tremor occurred with similar frequency in both groups. There was a striking difference in the frequency of single and multiple seizures: 43 cases (13.5%) in the citalopram group and 1 case (1.6%) with a single seizure in the escitalopram group (p = 0.0065). Discussion and conclusions. At comparable ingested doses of the S-enantiomer, the symptom profile for citalopram and escitalopram intoxications is similar except for seizures that occur more frequently in citalopram than in escitalopram poisoning.

Acute plant poisoning: Analysis of clinical features and circumstances of exposure

Introduction. Human contact with potentially toxic plants, which may occur through abuse or by accident or attempted suicide, is frequent and sometimes results in clinically significant toxicity. Objective. The aim of the present study was to identify which plants may lead to severe poisoning, and to define the clinical relevance of plant toxicity for humans in Switzerland. Methods. We analyzed 42 193 cases of human plant exposure and 255 acute moderate, severe, and lethal poisonings, which were reported to the Swiss Toxicological Information Centre between January 1995 and December 2009. Results. Plant contact was rarely responsible for serious poisonings. Lethal intoxications were extremely rare and were caused by plants with cardiotoxic (Taxus baccata) or mitosis-inhibiting (Colchicum autumnale) properties. Conclusions. Most often, plant contact was accidental and patients remained asymptomatic or developed mild symptoms, which fully resolved within a short time.

Seizures after single-agent overdose with pharmaceutical drugs: Analysis of cases reported to a poison center

Abstract Context. Seizures during intoxications with pharmaceuticals are a well-known complication. However, only a few studies report on drugs commonly involved and calculate the seizure potential of these drugs. Objectives. To identify the pharmaceutical drugs most commonly associated with seizures after single-agent overdose, the seizure potential of these pharmaceuticals, the age-distribution of the cases with seizures and the ingested doses. Methods. A retrospective review of acute single-agent exposures to pharmaceuticals reported to the Swiss Toxicological Information Centre (STIC) between January 1997 and December 2010 was conducted. Exposures which resulted in at least one seizure were identified. The seizure potential of a pharmaceutical was calculated by dividing the number of cases with seizures by the number of all cases recorded with that pharmaceutical. Data were analyzed using descriptive statistics. Results. We identified 15,441 single-agent exposures. Seizures occurred in 313 cases. The most prevalent pharmaceuticals were mefenamic acid (51 of the 313 cases), citalopram (34), trimipramine (27), venlafaxine (23), tramadol (15), diphenhydramine (14), amitriptyline (12), carbamazepine (11), maprotiline (10), and quetiapine (10). Antidepressants were involved in 136 cases. Drugs with a high seizure potential were bupropion (31.6%, seizures in 6 of 19 cases, 95% CI: 15.4–50.0%), maprotiline (17.5%, 10/57, 95% CI: 9.8–29.4%), venlafaxine (13.7%, 23/168, 95% CI: 9.3–19.7%), citalopram (13.1%, 34/259, 95% CI: 9.5–17.8%), and mefenamic acid (10.9%, 51/470, 95% CI: 8.4–14.0%). In adolescents (15–19y/o) 23.9% (95% CI: 17.6–31.7%) of the cases involving mefenamic acid resulted in seizures, but only 5.7% (95% CI: 3.3–9.7%) in adults (≥ 20y/o; p < 0.001). For citalopram these numbers were 22.0% (95% CI: 12.8–35.2%) and 10.9% (95% CI: 7.1–16.4%), respectively (p = 0.058). The probability of seizures with mefenamic acid, citalopram, trimipramine, and venlafaxine increased as the ingested dose increased. Conclusions. Antidepressants were frequently associated with seizures in overdose, but other pharmaceuticals, as mefenamic acid, were also associated with seizures in a considerable number of cases. Bupropion was the pharmaceutical with the highest seizure potential even if overdose with bupropion was uncommon in our sample. Adolescents might be more susceptible to seizures after mefenamic acid overdose than adults. “Part of this work is already published as a conference abstract for the XXXIV International Congress of the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) 27–30 May 2014, Brussels, Belgium.” Abstract 8, Clin Toxicol 2014;52(4):298.

Acute toxicity associated with the recreational use of the novel dissociative psychoactive substance methoxphenidine

Abstract Introduction. Methoxphenidine is a novel dissociative designer drug of the diarylethylamine class which shares structural features with phencyclidine (PCP), and is not at present subject to restrictive regulations. There is very limited information about the acute toxicity profile of methoxphenidine and the only sources are anonymous internet sites and a 1989 patent of the Searle Company. We report a case of analytically confirmed oral methoxphenidine toxicity. Case details. A 53-year-old man was found on the street in a somnolent and confusional state. Observed signs and symptoms such as tachycardia (112 bpm), hypertension (220/125 mmHg), echolalia, confusion, agitation, opisthotonus, nystagmus and amnesia were consistent with phencyclidine-induced adverse effects. Temperature (99.1°F (37.3°C)) and peripheral oxygen saturation while breathing room air (99%) were normal. Laboratory analysis revealed an increase of creatine kinase (max 865 U/L), alanine aminotransferase (72 U/L) and gamma-glutamyl transpeptidase (123 U/L). Methoxphenidine was identified by a liquid chromatography tandem mass spectrometry toxicological screening method using turbulent flow online extraction in plasma and urine samples collected on admission. The clinical course was favourable and signs and symptoms resolved with symptomatic treatment. Conclusion. Based on this case report and users’ web reports, and compatible with the chemical structure, methoxphenidine produces effects similar to those of the arylcyclohexylamines, as PCP.

Low-dose exposure to Veratrum album in children causes mild effects - a case series

Introduction. White or false hellebore (Veratrum album) has a toxicological relevance because of the potential for misidentification of this plant as yellow gentian (Gentiana lutea). Case series. We report a retrospective case series of 11 children (8–12 years) with accidental intake of V. album at a youth camp where they had collected herbs for preparing fresh herb tea. Two children (18%) remained asymptomatic. Nine (82%) developed mild gastrointestinal symptoms, six (55%) presented neurological symptoms, and three (27%) showed bradycardia. All children recovered completely within 10 h of ingestion. The plant was identified at the emergency department; however, detection of veratridine and cevadine by means of high-performance liquid chromatography–Mass spectrometry from the blood of the child with the most severe symptoms was negative (limit 0.01 ng/mL). Discussion. Veratrum species contain more than 200 different alkaloids, which are the principal toxins and are responsible for most clinical symptoms. There are likely multiple mechanisms of toxicity and some of them are only partially understood. The opening of voltage-gated sodium channels is probably one of the most relevant pathophysiological mechanisms. Conclusions. Veratrum album intoxication in children demonstrated the same clinical course as observed in adults. Accidental ingestion of a low dose of the plant had a favorable outcome with supportive care.

An 11-month-old boy with psychomotor regression and auto-aggressive behaviour.

An 11-month-old Swiss boy was brought to his paedi-atrician. He had been in good health and had developednormally until then, but his parents mentioned that overthe previous 2 weeks, the child no longer laughed orplayed, was becoming more and more restless, and sleptonly 1 to 2 h a night. He was no longer able to crawl andto stand up, and he had lost weight. Clinical examina-tion revealed swollen hands and feet with skin desqua-mation, axial hypotonia and brisk reflexes. The childsweated profusely, refused to crawl or stand, showedstereotypic movements of the hands (kneading) andrepeatedly bit objects or his own hands.Upon admission to the regional hospital, blood cellcount, electrolytes, blood gas analysis, thyroid hormonesand cerebrospinal fluid were normal. Liver and kidneyparameters were normal, but plasma LDH and CK wereincreased to 724 U/l (normal <296 U/l) and to 270 U/l(normal <234 U/l), respectively. EEG, chest X-ray film,abdominal sonography, cranial CT scan and a musclebiopsywereallnormal.Differentialdiagnosisatthatpointincludedaviralinfection,neuroborreliosis,andcoeliacdis-ease,butlaboratoryinvestigationsremainedinconclusive.Two further weeks later, the symptoms persisted andthe child was referred to a secondary centre. Clinicalfindingswereunchanged;routinelaboratorystudieswereagain normal. EEG, brain MRI, and investigations for ametabolic disorder (ammonia, uric acid, amino acids,organic acids, acylcarnitines and mucopolysaccharides)were normal. The diagnosis remained obscure. The childwasreferredforfurtherevaluationofseverepsychomotorregression with autistic features of unknown aetiology.The child was admitted to our hospital at age 14months.Lengthandweight,thathadbeenatP50atage11months, had declined to P3–10. The child appeared ex-hausted and irritable and sweated profusely. The handsandfeetwereswollen,erythematousandtender(Fig. 1).Afinemaculo-papularexanthemawaspresentonthetrunk.There was muscular hypotrophy with peripheral oedemaand axial hypotonia. Physical findings included tachy-cardia (160–180/min) and arterial hypertension (140/80 mmHg). The boy refused to stand, but would sit in acrouchedposition,hadasadandapatheticlook,tooklittleinterestinhissurroundingsandwouldoccasionallybitehishands and feet. A review of a videotape obtained duringthe first hospitalisation several weeks earlier showed thatall features had been even more marked at that time.Abdominal sonography showed no signs of a tumouror renal disease; chest radiography and MIBG-scintigra-phy showed no signs of a tumour. Echocardiographyshowed no signs of cardiomyopathy. An ophthalmologi-cal examination did not reveal corneal or lenticularabnormalities. An afebrile seizure occurred during hos-pitalisation: EEG and cerebral spinal fluid were againnormal.Arterialhypertensionandtachycardiahadagoodresponse to beta-blockers. Thyroid hormones were nor-mal, but urinary excretion of epinephrine (epinephrine/creatinine: 86 nmol/mmol; normal<25 nmol/mmol),norepinephrine (norepinephrine/ creatinine: 263 nmol/mmol; normal <55 nmol/mmol), dopamine (dopamine/creatinine 1192 nmol/mmol; normal <590 nmol/mmol)and HMA and VMA (HMA/creatinine 6.9 lmol/mmol;normal<4.7 lmol/mmol)wereelevated.Because of developmental regression, muscularhypotonia,anorexia,andauto-aggressivebehaviourwithbiting of feet and fingers, Lesh-Nyhan syndrome wasconsideredbut excluded bynormallevelsofuricacidandpurine pattern in plasma and urine. Fabry disease wasconsidered because of hypertension and pain in handsand feet but ruled out by normal a-galactosidase activityin leukocytes. Finally, a specific question to the child’sparents allowed a presumptive diagnosis.

Minimal dose for severe poisoning and influencing factors in acute human clozapine intoxication: a 13-year retrospective study.

Objectives:Clozapine is an atypical antipsychotic drug used in the treatment of resistant schizophrenia. Intoxications with this drug are frequently observed. The aim of the present study was to identify a minimal dose and the dose bearing a 50% risk of developing moderate or severe intoxication symptoms. We also investigated the influence of age, sex, effect of decontamination measures, and pretreatment with clozapine on the severity of poisoning. Methods:A retrospective case study of 73 acute clozapine monointoxications reported by physicians to the Swiss Toxicological Information Centre between 1995 and 2007. Results:The most common symptoms were central nervous system depression (63.1%), tachycardia (39.7%), restlessness/agitation (16.4%), confusion/disorientation (15.1%), dysarthria (15.1%), arterial hypertension (10.9%), bradykinesia (9.6%), respiratory depression (9.6%), and QTc prolongation (8.2%). We found a significant correlation between ingested clozapine dose and severity of poisoning. The minimal dose for both moderate and severe intoxications was 0.1 g. The dose for a 50% risk of developing moderate or severe intoxications was 0.9 g in patients older than 50 years and 14.5 g in patients younger than 50 years. Patients older than 50 years had a significantly increased risk for a severe clinical course (odds ratio, 6.41; 95% confidence interval, 1.88-21.90). We found no significant correlation between pretreatment, sex or decontamination, and the severity of the intoxication. Conclusions:Moderate and severe clozapine intoxications can already occur after ingestion of doses in the low therapeutic range, especially in patients older than 50 years. Poisoned patients have to be monitored for central nervous system depression, tachycardia, blood pressure abnormalities, respiratory depression, and QTc prolongation.

Accidental intakes of remedies from complementary and alternative medicine in children—analysis of data from the Swiss Toxicological Information Centre

The use of complementary and alternative medicine (CAM) in Switzerland is rather high, and therefore, the occurrence of accidental intakes of CAM remedies by children and associated intoxications is to be expected. In the present study, the inquiries to the Swiss Toxicological Information Centre that took place from 1998 until 2007 and concerned accidental, unintended intakes of CAM remedies by children were analysed. Inquiries for information were performed by concerned care-givers, physicians, pharmacists and others in case of acute accidental intake of CAM remedies. Feedbacks from physicians about paediatric patients with acute intoxication possibly associated with the accidental ingestion of CAM remedies were as well considered. During the study period, 3,158 accidental intakes of CAM remedies (1,015 of herbal and 2,143 of homeopathic remedies) were reported, corresponding to 8.6% of all reported accidental intakes of pharmaceutical products by children. No significant increase of the yearly number of accidental intakes of CAM remedies was detected during the study period. There was no accidental intake of CAM remedies leading to severe signs or symptoms. Concerning the herbal remedies, three intoxications of moderate and 28 of minor severity were reported. Nine children with intoxication from homeopathic remedies were reported, with minor symptoms only. All other accidental intakes of CAM remedies did not lead to intoxications and evolved without manifestations. The data show that accidental, unintended intake of CAM remedies happened in children, but developed mostly harmlessly. Comparing herbal with homeopathic remedies, accidental intakes with homeopathic remedies were more common, but intoxications associated with manifestations were observed more frequently with herbal remedies.

Acute thiopurine overdose : analysis of reports to a National Poison Centre 1995-2013

Literature regarding acute human toxicity of thiopurines is limited to a handful of case reports. Our objectives were to describe all cases of overdose with thiopurines reported to the Swiss Toxicological Information Centre between 1995–2013. A retrospective analysis was performed to determine circumstances, magnitude, management and outcome of overdose with these substances. A total of 40 cases (14 paediatric) were reported (azathioprine, n = 35; 6-mercaptopurine, n = 5). Of these, 25 were with suicidal intent, 12 were accidental and 3 were iatrogenic errors. The magnitude of overdose ranged from 1.5 to 43 (median 8) times the usual dose in adults. Twelve cases (30%) had attributable symptoms. The majority of these were minor and included gastrointestinal complaints and liver function test and blood count abnormalities. Symptoms were experienced by patients who took at least 1.5-times their usual daily thiopurine dose. Overdoses over two or more consecutive days, even if of modest size, were less well tolerated. One case of azathioprine and allopurinol co-ingestion over consecutive days led to agranulocytosis. Decontamination measures were undertaken in 11 cases (10 activated charcoal, 1 gastric lavage) and these developed fewer symptoms than untreated patients. This study shows that acute overdoses with thiopurines have a favourable outcome in the majority of cases and provides preliminary evidence that gastrointestinal decontamination with activated charcoal may reduce symptom development after overdose of these substances if patients present to medical services soon after ingestion.