Anaphylactic Death Research Articles

A méh- vagy darázscsípés okozta anafilaxiás sokk vizsgálata a triptáz enzim és a méh-, illetve darázsméreg specifikus immunglobulin E szintek vérből történő meghatározása alapján, egyes rendkívüli haláleseti eljárásokban

Aim: Systemic allergic reactions triggered by bee and wasp venom affect approximately 3% of adults, and in severe cases, can lead to anaphylactic reactions and death. The exact cause of extraordinary deaths resulting from insect stings is often not determined in a significant number of cases. The aim of this study is to provide guidance through methodological recommendations to investigate the precise cause of deaths presumably resulting from insect stings, specifically focusing on uncovering the facts and causes of anaphylaxis. Methodology: The study reviews literature related to anaphylaxis caused by insect stings and animal toxins, as well as its immunological background. It seeks to translate the information found in the literature into the realm of official activities related to extraordinary deaths. The study also summarises knowledge about groups of animals in Hungary that are medically significant due to their venom, providing guidance for on-site recognition, search, documentation, and recording of the most common Hymenoptera species with venom capable of frequently inducing anaphylactic reactions. Findings: The key to diagnosing deaths caused by anaphylaxis lies in crime scene investigation. The attending medical doctor must recognise the symptoms of insect stings and ensure the collection of a blood sample for allergological purposes. A special blood collection kit has been assembled for this purpose. The blood sample, which must be stored at 2–8ºC, should be sent to the Semmelweis University Institute of Laboratory Medicine within 2 days. By measuring the level of tryptase enzyme in the blood sample and detecting the presence of specific immunoglobulin E for the venom of the respective bee or wasp species, the cause of the anaphylactic reaction can be confirmed. The crime scene investigation team should also make an effort to locate and secure the potential insect species responsible for the sting. If the forensic entomologist successfully identifies the species, it facilitates the specific IgE allergological examination for the respective venom. Value: In cases of death resulting from insect stings, the cause is often not determined due to lack of proper caution and appropriate methods. The procedural approach recommended in the study establishes the basis for determining the precise cause of death in cases of suspected insect stings.

Serum metabolomics analysis reveals potential biomarkers of penicillins-induced fatal anaphylactic shock in rats

Immunoglobulin E (IgE)-mediated immediate hypersensitivity reactions are the most concerning adverse events after penicillin antibiotics (PENs) administration because of their rapid progression and potential for fatal outcome. However, the diagnosis of allergic death is a forensic challenge because it mainly depends on nonspecific characteristic morphological changes, as well as exclusion and circumstantial evidence. In this study, an untargeted metabolomics approach based on liquid chromatography-mass spectrometry (LC-MS) was used to screen potential forensic biomarkers of fatal anaphylactic shock induced by four PENs (benzylpenicillin (BP), amoxicillin (AMX), oxacillin (OXA), and mezlocillin (MEZ)), and analyzed the metabolites, metabolic pathway and the mechanism which were closely related to the allergic reactions. The metabolomics results discovered that a total of 24 different metabolites in all four anaphylactic death (AD) groups, seven of which were common metabolites. A biomarker model consisting of six common metabolites (linoleic acid, prostaglandin D2, lysophosphatidylcholine (18:0), N-acetylhistamine, citric acid and indolelactic acid) AUC value of Receiver Operating Characteristic (ROC) curve was 0.978. Metabolism pathway analysis revealed that the pathogenesis of PENs-induced AD is closely related to linoleic acid metabolism. Our results revealed that the metabolomic profiling has potential in PENs-induced AD post-mortem diagnosis and metabolic mechanism investigations.

Association Between Cardiovascular Disease and Death by Anaphylaxis: A 20-Year Retrospective Study in Queensland, Australia.

Despite its severity, anaphylaxis carries a low mortality rate of less than 1%, making the cohort seen in the forensic pathology setting a small and unique subset of the majority of cases of anaphylaxis in the community. Clinically, cardiovascular disease has been recognized as a risk factor for fatal anaphylaxis; however, there is scant forensic pathology research investigating this risk factor, whereas autopsy textbooks emphasize physical respiratory changes seen in the broader clinical cohort. This 20-year retrospective study examined all fatal anaphylactic deaths in the state of Queensland, Australia, to document the underlying disease of the cases, tryptase levels, triggers, and postmortem findings. Our study found that cardiovascular disease was prevalent in 83.3% of cases of fatal anaphylaxis. Although asthma was prevalent in food-related fatal anaphylaxis (60%) in our cohort, it was poorly represented overall (28%), in contrast to clinical research. Additionally, only 43% of cases showed respiratory changes that were greater than mild. Our findings emphasize the difference between the clinical and postmortem anaphylaxis cohorts, and provide autopsy evidence of a potential role of cardiovascular disease in fatal anaphylaxis.

Anaphylactic deaths: A retrospective study of forensic autopsy cases from 2009 to 2019 in Shanghai, China

Anaphylaxis is a rare but well-known cause of sudden unexpected death, although data from forensic autopsies in anaphylactic deaths are limited. Herein, a retrospective study of a series of allergic deaths from 2009 through 2019 in Shanghai, China, was conducted to investigate the demographic, medical, and forensic pathological characteristics of fatal anaphylaxis to improve medicolegal understanding on anaphylactic death. Sixty-two autopsy cases of anaphylactic death were registered in this study. Males dominated the cases (74.2%) against females (25.8%), with an average age of 38.8 years. Medications (98.4%), particularly antibiotics (72.6%), were the most frequent cause of anaphylaxis, and 44 cases (71.0%) occurred in clinics administered illegally by unlicensed clinicians. The anaphylactic symptoms began within a few minutes to less than 1 h in 53 cases, with dyspnea (56.5%) and sudden shock (46.8%) being the most common clinical signs. Thirty cases (48.4%) of anaphylaxis resulted in death within 1 h. Laryngeal edema and multiple tissue eosinophil infiltration (85.5%) were the most prevalent autopsy findings, followed by pulmonary edema and congestion (24.2%), which were considered to be non-specific but suggestive. The comorbidities were mainly cardiovascular disease (33.9%), pneumonia (8.1%) and asthma (8.1%). Serum IgE were measured in 11 of 62 cases, ranging from 43.3 to 591 IU/ml, severed as a helpful marker. Therefore, we suggested a thorough analysis of allergen exposure, clinical history and autopsy findings is required for the diagnosis of anaphylactic death currently.

Death Due to Anaphylactic Reaction: The Role of the Forensic Pathologist in an Accurate Postmortem Diagnosis.

Background and Objectives: The diagnosis of anaphylaxis comprehensively depends on both situational information and laboratory investigations. For this purpose, serum tryptase concentration is examined as an indicator of systemic mast cell mediator release, linked to an underlying anaphylactic process. Increased levels of tryptase may occur in some events different from anaphylaxis, but usually information from crime scene investigations is lacking and autoptic findings are not specific. For legal reasons, it is required to achieve a definite diagnosis of mast cell degranulation that can lead to a certain diagnosis of death from anaphylaxis. Immunohistochemistry seems to be a relatively simple, reliable, and easily repeatable method that can assist the forensic pathologist in the differential diagnosis of death from anaphylaxis. Materials and Methods: This work provides an overview of the current literature on immunohistochemical methods useful in the determination process of anaphylactic-related deaths. A systematic search, according to the PRISMA statement, was performed in databases to identify studies investigating immunohistochemical targets related to anaphylaxis death. Results: This work underscores the importance of anaphylaxis mediators such as tryptase, CD117, and chymase in the immunohistochemical analysis of anaphylactic deaths. Conclusions: According to the reviewed literature, the diagnosis of death due to anaphylaxis should depend not just on the suspicion of an anaphylactic reaction but also on confirming mast cell degranulation through the identification of IHC positivity for inflammatory mediators, particularly in the respiratory tract.

Postmortem Biochemistry and Immunohistochemistry in Anaphylactic Death Due to Hymenoptera Sting: A Forensic Case Report

Postmortem assessment of anaphylactic death is a challenge for forensic pathologists. One of the most frequent elicitors of anaphylaxis is insect venom. Here, a case of anaphylactic death due to Hymenoptera stings is reported to highlight the contribution of postmortem biochemistry and immunohistochemistry in assessing the cause of death. A 59-year-old Caucasian man working on his farm was presumably stung by a bee and died. He had a history of previous sensitization to insect venom. The autopsy revealed no signs of insect puncture, mild edema of the larynx, and foamy edema in the bronchial tree and lungs. Routine histology showed endo-alveolar edema and hemorrhage, bronchospasm, and scattered bronchial obstruction due to mucus hyperproduction. Biochemical analysis was performed, and serum tryptase was equal to 189 µg/L, total IgE was 200 kU/L, and specific IgE dosage was positive for bee and yellow jacket species. Immunohistochemistry for tryptase detection was carried out, revealing mast cells and degranulated tryptase expression in the larynx, lungs, spleen, and heart. These findings led to the diagnosis of anaphylactic death due to Hymenoptera stings. The case highlights that the role of biochemistry and immunohistochemistry in the postmortem assessment of anaphylactic reactions should be stressed by forensic practitioners.

Alpha Gal allergy and its connection to mammalian derived medical products.

Allergists have identified populations with high titers of anti-alpha-gal (galactose-alpha1,3-galactose) IgE due to a tick bite that adversely react after exposure to alpha-gal (e.g., alpha-gal syndrome (AGS)). The alpha-gal IgE sensitized individual has been well documented to experience adverse events after administration of mammalian-derived therapeutic products including anaphylactic shock and death. The aim of this study was to demonstrate presence of alpha gal in various medical products.

Expression of FcεRIα and tryptase in human lung tissue during drug-induced anaphylactic death

The diagnosis of drug-induced anaphylactic death is an important component of forensic medicine. The purpose of this study was to explore the expression of FcεRIα and tryptase in human lung tissue during drug-induced anaphylactic death and its value for forensic medicine. The expression of FcεRIα and tryptase in lung tissues of the drug-induced anaphylactic death group (n = 30) and control group (who died due to sudden cardiac death, falling from a height, or traffic accidents, n = 30) was detected by immunohistochemistry and immunofluorescence staining. Thedifference in FcεRIα and tryptase expression in the lung tissue between the drug-induced anaphylactic death group and the control group wasstatisticallysignificant (p < 0.05). The levels of FcεRIα and tryptase expression greatly increased in the lung tissue of the drug-induced anaphylactic death group, which may provide morphological evidence and a reference for the diagnosis of drug-induced anaphylactic death in forensic medicine.

Postmortem diagnostics of assumed suicidal food anaphylaxis in prison: a unique case of anaphylactic death due to peach ingestion

Suicidal ingestion of food which the victim is aware they are allergic to is an exceptional occurrence in the forensic field. To the best of our knowledge, no cases of suicidal food anaphylaxis have been reported to date. Therefore we present the first case described in the literature. A 30-year-old prisoner was found dead inside his cell with the remains of a peach remains next to his body, and a handwritten farewell note in his pocket. The autopsy revealed only non-specific findings, while laboratory investigations (serological, toxicological, histological, and immunohistochemical) played a pivotal role in determing the cause and manner of death. In particular, a high titer of both total and specific IgE antibodies was detected, as well as an increase of the tryptase level in cadaveric blood. Moreover, a massive concentration of salicylates was measured in the gastric contents. Microscopically, cellular residues characterized by a vegetal structure were observed in the gastric contents and elements suggestive of mast cells were detected in the glottis, lungs, and myocardium. The immunohistochemical investigation with anti-CD117 and anti-tryptase antibodies showed positivity for mast cells, some of which appeared degranulated. Such findings were entirely consistent with an acute systemic anaphylactic reaction triggered by allergy. Therefore, the prisoner’s death was attributed to self-induced food anaphylaxis caused by the ingestion of peaches. This conclusion was achieved based only on circumstantial data, anamnestic information, autopsy findings, and multiple laboratory results. This integrated approach should be used to pursue a post-mortem diagnosis of anaphylaxis.

Anaphylactic Death: A New Forensic Workflow for Diagnosis.

Anaphylaxis is a life-threatening or fatal clinical emergency characterized by rapid onset, and death may be sudden. The margin of certainty about the diagnosis of anaphylactic death is not well established. The application of immunohistochemical techniques combined with the evaluation of blood tryptase concentrations opened up a new field of investigation into anaphylactic death. The present study investigated eleven autopsy cases of anaphylactic death, carried out between 2005 and 2017, by the Departments of Forensic Pathology of the Universities of Foggia and Catania (Italy). An analysis of the medical records was carried out in all autopsies. Seven autopsies were carried out on males and four on females. Of the eleven cases, one showed a history of asthma, one of food ingestion, two of oral administration of medications, six did not refer any allergy history, and one subject was unknown. All cases (100%) showed pulmonary congestion and edema; 7/11 (64%) of the cases had pharyngeal/laryngeal edema and mucus plugging in the airway; only one case (9%) had a skin reaction that was found during external examination. Serum tryptase concentration was measured in ten cases, and the mean value was 133.5 µg/L ± 177.9. The immunohistochemical examination using an anti-tryptase antibody on samples from the lungs, pharynx/larynx, and skin site of medication injection showed that all cases (100%) were strongly immunopositive for anti-tryptase antibody staining on lung samples; three cases (30%) were strongly immunopositive for anti-tryptase antibody staining on pharyngeal/laryngeal samples; and eight cases (80%) were strongly immunopositive for anti-tryptase antibody staining on skin samples. We conclude that a typical clinical history, blood tryptase level >40 µg/L, and strongly positive anti-tryptase antibody staining in the immunohistochemical investigation may represent reliable parameters in the determination of anaphylactic death with the accuracy needed for forensic purposes.

Postmortem serum levels of beta tryptase and total ige in non-anaphylactic deaths

Anaphylactic deaths are a challenge during autopsy due to the minimal autopsy findings. The role of beta tryptase and IgE in the diagnosis of anaphylactic deaths is well established. However, contradicting studies challenge the veracity of these biomarkers as they are found to be raised even in non-anaphylactic deaths. In this study, the postmortem serum Beta Tryptase and IgE levels in various causes of deaths other than anaphylaxis was analyzed to find out its diagnostic significance and relevance in autopsy samples.

Blood exposure to graphene oxide may cause anaphylactic death in non-human primates

Abstract Toxicological evaluation of graphene oxide (GO) has been actively pursued under the context of large-scale industrial production and the potential for clinical translation. Nevertheless, the safety of GO remains largely debated, especially due to the lack of toxicological profile in higher mammals. Here we show that blood exposure to GO under the maximum safe starting dose may cause accidental death of mammals, including non-human primates (1 in 5 Macaca fascicularis and 7 in 121 mice), while remains general amenable in others. Elevated levels of immunoglobulin E and severe lung injury were found in dead animals, suggesting the GO-induced acute anaphylactic reactions. Noticeably, we did not observe anaphylactic reactions and deaths for two other carbon nanomaterials, including single-walled carbon nanotubes and nanodiamonds. This difference might arise from the long in-vivo circulating time of two-dimensional GO materials. This study thus highlights the urgent need to evaluate the hypersensitivity risks of graphene and other nanomaterials.

REAÇÕES ANAFILÁTICAS EM ANESTESIA

A despeito da segurança dos procedimentos anestésicos ter aumentado nas últimas décadas, a anafilaxia tem sido reconhecida como uma das causas mais comuns de morte na prática médica. As manifestações clínicas apresentam com um vasto espectro, variando desde reações de hipersensibilidade leve a choque anafilático e morte. Qualquer substância utilizada durante uma anestesia pode desencadear reação anafilática, sendo os bloqueadores neuromusculares os mais frequentes (50 a 70 %), seguidos pelo látex (12-16,7%) e antibióticos (15%). No contexto intraoperatório, o diagnóstico torna-se mais difícil e tardio. O rápido reconhecimento ou a suspeita clínica de anafilaxia intraoperatória devem ser seguidas de conduta adequada a fim de interromper o contato com o agente causal e a perpetuação da resposta imunológica.

Synthetic antivenoms for snakebites: a slithering road!

Since Adam and Eve, humankind has been equally frightened and fascinated by snakes. The ancient Egyptians worshipped the cobra, which decorate sarcophagi and the famous mask of Tutankhamun. Even today, the snake is integral to the Staff of Asclepius, a symbol of medicine. To some extent, medicine has forgotten about the snake, however, bites from venomous snakes still pose a deadly impact on people in low-and middle-income countries. It is estimated that venomous snakes kill between 81,000 and 137,000 people every year, and maim around 400,000, which represents a huge impact both on families and social economics. Around 125 years ago, Calmette began to produce antivenom serum for snakebite victims. Since then, production methods have not changed significantly; then and now, antivenom is made by immunizing animals. Isolated antibodies can neutralize some of the most lethal toxins, thereby saving many lives. However, there is still a need for animals such as horses or sheep, as well as a snake farm, in order to acquire enough venom for immunization procedures. Animal-derived antibodies pose a threat, because they are foreign components injected into the human body, which can give rise to adverse immunogenic reactions. In a worst-case scenario this can lead to anaphylactic shock and death. Synthetic antivenom, is an interesting avenue, which could reduce or entirely remove the need for immunized animals and snake farms. Synthetic antivenoms could be made to high purity and eliminate many current challenges, such as batch-to-batch variations, high costs, limited shelf life and the need for ‘cold-chain’ transportation.

Expression of CD63 in Lung Tissue of Guinea Pigs Dying of Anaphylactic Shock.

Objective To study the protein expression of cluster of differentiation 63 （CD63） in lung tissues of guinea pigs that died of anaphylactic shock and discuss the diagnostic value of CD63 for death from anaphylactic shock. Methods Twenty guinea pigs were randomly divided into control group, anaphylactic shock immediate death group, cold storage group （4 ℃ for 48 h） and frozen group （-20 ℃ for 7 d）. The animal model of guinea pigs that died of anaphylactic shock was established with human mixed serum injection. The expression changes of CD63 protein and CD63 mRNA in lung tissues were detected by hematoxylin-eosin （HE） staining, immunohistochemical staining, Western blotting, enzyme-linked immunosorbent assay （ELISA） and real-time RT-PCR. Results HE staining results showed congestion, and edema of lung tissues, and eosinophil infiltration in the anaphylactic shock groups. Western blotting analysis results showed that the expression of CD63 protein in the lung tissues of guinea pigs that died of anaphylactic shock was significantly higher than that in the control group （P<0.05）. Comparison between the anaphylactic shock groups was made, and the differences had no statistical significance. The results of immunohistochemical staining and real-time RT-PCR were consistent with that of Western blotting. ELISA results showed that CD63 protein expression in the immediate death group was higher than that in the control group （P<0.05）. Conclusion The expression of CD63 protein and CD63 mRNA in the lung tissues of guinea pigs that died of anaphylactic shock is significantly enhanced. Animal carcasses which were put in cold storage for 48 h and frozen for 7 d do not affect the examination of the above indicators. CD63 protein is expected to become an auxiliary diagnostic indicator of death from anaphylactic shock.

Safety and Toxicity of Recombinant Methioninase and Polyethylene Glycol (PEG) Recombinant Methioninase in Primates.

Methionine (MET) is a general metabolic therapeutic target in cancer, whereby cancer cells have an elevated requirement for MET, termed MET dependence. We have developed recombinant L-methionine α-deamino-γ-mercaptomethane lyase (recombinant methioninase [rMETase, EC 4.4.1.11]) as targeted therapy of all cancer types. Pharmacokinetics, MET depletion, antigenicity, and toxicity of rMETase were examined in macaque monkeys. Pharmacokinetic analysis showed that rMETase was eliminated with a T1/2 of 2.49h. A 2-week i.v. administration of 4000units/kg every 8h/day for 2weeks resulted in a steady-state depletion of plasma MET to less than 2μM. The only manifest toxicity was decreased food intake and slight weight loss. Serum albumin and red-cell values declined transiently during treatment. Rechallenge on day 28 resulted in anaphylactic shock and death in one animal. Pretreatment with hydrocortisone prevented the anaphylactic reaction. Anti-rMETase antibodies (at 10-3) were found after the first challenge, increased to 10-6 after the fourth challenge, and decreased to 10-2 by 2months post-therapy. Therefore, the therapeutic potential of rMETase is limited by its short plasma half-life and immunologic effects, including high antibody production in mice and anaphylactic reactions in monkeys. To overcome these limits, rMETase has been coupled to methoxypolyethylene glycol succinimidyl glutarate polyethylene glycol (MEGC-PEG-5000). The pharmacokinetics, antigenicity, and toxicity of MEGC-PEG-rMETase in macaque monkeys were evaluated using an escalating-dose strategy. In pharmacokinetic studies, a single 4000units/kg dose showed that MEGC-PEG-rMETase holoenzyme activity was eliminated with a biological half-life of 1.3h, and the MEGC-PEG-rMETase apoenzyme was eliminated with a biological half-life of 90h, a 36-fold increase compared with non-PEGylated rMETase. The disparity in the T½ of the apoenzyme and the holoenzyme reflects the loss of co-factor pyridoxal-L-phosphate of the circulating MEGC-PEG-rMETase. A 7-day i.v. administration of 4000units/kg every 12h resulted in a steady-state depletion of plasma MET to <5μmol/L. The only manifest toxicity was decreased food intake and slight weight loss. Red cell values and hemoglobin declined transiently. Subsequent challenges did not result in any immunologic reactions. Anti-MEGC-PEG-rMETase antibodies were 100- to 1000-fold less than antibodies elicited by naked rMETase, thereby suggesting clinical potential of MEGC-PEG-rMETase as a broad anticancer agent.

A longitudinal study of hymenoptera stings in preschool children.

Insect venom is the second most common cause of anaphylaxis outside of medical encounters. Stings cause over 20% of all anaphylactic deaths and 7% of anaphylaxis in children. To date, there have been no longitudinal studies of insect sting events or allergy in preschool children. A prospective longitudinal nested observational study in the BASELINE Birth Cohort Study (n=2137). Sting-related questions were asked at 6 and 12months and 2 and 5years. Skin prick testing (SPT) was performed at 2 and 5years. SpIgE testing was performed on selected cases at 2years. Seventy-seven children (6.8%) were stung by the age of 2. Of these, 25 (32.5%) reported adverse reactions (four systemic). Eleven (0.9%) had positive SPT at 2years (eight bee, two wasp, one both). Four stung children had positive SPT. Two (one stung, one never stung) had positive spIgE to a venom component at 2years. A total of 268 children (21.9%) were stung by 5years, 144 (52.1%) reporting local reactions and none systemic. Four children (0.4%) had positive SPT at 5years: one bee and three wasp. Of the 11 SPT-positive children at 2years, none were still positive at 5years. This is the first longitudinal study of the natural history of hymenoptera stings and allergy in preschool children. Hymenoptera venom allergy is less common in this cohort than in adults. Systemic reactions were not medically documented in this population, in keeping with previous literature. This study confirms the poor correlation of IgE sensitization to venom with sting allergy and does not support the common parental request to screen children for sting allergy.

Anaphylactic cardiovascular collapse and Kounis syndrome: systemic vasodilation or coronary vasoconstriction?

The first reported human anaphylactic death is considered to be the Pharaoh Menes death, caused by a wasp sting. Currently, anaphylactic cardiovascular events represent one of most frequent medical emergencies. Rapid diagnosis, prompt and appropriate treatment can be life saving. The main concept beyond anaphylaxis lies to myocardial damage and ventricular dysfunction, thus resulting in cardiovascular collapse. Cardiac output depression due to coronary hypoperfusion from systemic vasodilation, leakage of plasma and volume loss due to increased vascular permeability, as well as reduced venous return, are regarded as the main causes of cardiovascular collapse. Clinical reports and experiments indicate that the human heart, in general, and the coronary arteries, in particular, could be the primary target of the released anaphylactic mediators. Coronary vasoconstriction and thrombosis induced by the released mediators namely histamine, chymase, tryptase, cathepsin D, leukotrienes, thromboxane and platelet activating factor (PAF) can result to further myocardial damage and anaphylaxis associated acute coronary syndrome, the so-called Kounis syndrome. Kounis syndrome with increase of cardiac troponin and other cardiac biomarkers, can progress to heart failure and cardiovascular collapse. In experimental anaphylaxis, cardiac reactions caused by the intracardiac histamine and release of other anaphylactic mediators are followed by secondary cardiovascular reactions, such as cardiac arrhythmias, atrioventricular block, acute myocardial ischemia, decrease in coronary blood flow and cardiac output, cerebral blood flow, left ventricular developed pressure (LVdp/dtmax) as well as increase in portal venous and coronary vascular resistance denoting vascular spasm. Clinically, some patients with anaphylactic myocardial infarction respond satisfactorily to appropriate interventional and medical therapy, while anti-allergic treatment with antihistamines, corticosteroids and fluid replacement might be ineffective. Therefore, differentiating the decrease of cardiac output due to myocardial tissue hypoperfusion from systemic vasodilation and leakage of plasma, from myocardial tissue due to coronary vasoconstriction and thrombosis might be challenging during anaphylactic cardiac collapse. Combined antiallergic, anti-ischemic and antithrombotic treatment seems currently beneficial. Simultaneous measurements of peripheral arterial resistance and coronary blood flow with newer diagnostic techniques including cardiac magnetic resonance imaging (MRI) and myocardial scintigraphy may help elucidating the pathophysiology of anaphylactic cardiovascular collapse, thus rendering treatment more rapid and effective.

Diagnostic role of serum tryptase in anaphylactic deaths in forensic medicine: a systematic review and meta-analysis.

Postmortem diagnosis of sudden death due to anaphylaxis can be very difficult due to the non-specific pathological findings in forensic practice. Postmortem serum tryptase has been used as an indicator of possible ante-mortem anaphylaxis. Though many previous studies have been conducted to explore the diagnostic significance of serum tryptase for lethal anaphylaxis, inconsistent results were documented. In this study, we made a retrospective study and presented a systematic review and meta-analysis that aims to summarize the diagnostic significance of postmortem serum tryptase in the deceased with and without anaphylactic shock and to calculate a cutoff value for future reference in the identification of deaths due to anaphylactic shock. A complete literature search in the PubMed, Cochrane Library, CNKI and Embase databases (published prior to March 1st, 2017) was performed. The quality of the eligible literature was evaluated according to the Newcastle-Ottawa Quality Assessment Scale (NOS), and the relevant data was extracted. The procedure of meta-analysis was performed by RevMan 5.3 software. Subgroup analysis was performed according to different causes of death. A total of nine studies with 296 patients were identified. The NOS of each included study was equal to 7. The results indicated that high concentrations of tryptase were significantly associated with anaphylactic shock when compared to the other causes of death. The weighted mean difference (WMD) was 29.53 (95% CI = 7.58-51.47, p = 0.008). Similar results were detected in the subgroup analysis when compared to deaths due to cardiovascular disease (CVD). However, no obvious elevation of tryptase in decedents with CVD compared to the other cause of death was observed (WMD = 4.42, 95% CI = -0.94-9.79). We concluded that high serum tryptase is a promising diagnostic biomarker for deaths due to anaphylactic shock, especially when it is higher than 30.4μg/L.

Post mortem determination of (β)-tryptase for the diagnosis of anaphylaxis: looking for a reasonable cut-off.

Anaphylactic deaths represent a critical issue for forensic pathologists and its post-mortem diagnosis requires several steps in order to formulate a correct and reliable diagnosis, which is not always reachable in a forensic setting. This is the reason why, especially in deaths occurred out-of-hospital or in an unclear accidental manner, reliable diagnostic methods to confirm or exclude anaphylaxis would be of great value (1)