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The diagnosis of fatal anaphylaxis can be difficult for clinical features may not always be evident in necropsy. Therefore post mortem determination of tryptase and other blood parameters can be helpful in verifying the diagnosis. We compared post mortem tryptase, histamine and diamine oxidase (DAO) serum levels of two patients who had died after a Hymenoptera sting and one patient who died of bronchospasm during anaesthesia with data obtained from 55 control subjects who had died from other causes than anaphylaxis. In the three anaphylactic cases, serum tryptase level was 880, 68 and 200 μg/l (normal range in living subjects: <11.4 μg/l), histamine was 37.5, 8.5 and 23.2 ng/ml (normal range: <0.3 ng/ml) and DAO was 1, 30 and 4 U/ml (normal range 10-30 U/ml), respectively. Values in the control group were as follows: tryptase 1-340 μg/l (mean 24.2 ± 58.2), histamine 5.0-22.0 ng/ml (mean 14.7 ± 3.9) and DAO 0-114 U/ml (mean 21.1 ± 27.8). 19/55 (34.5%) of the controls had elevated tryptase levels >11.4 μg/l, with four of them showing values >45 μg/ml. Significantly higher histamine levels were seen in blood samples taken more than 24h post mortem (p<0.05), whereas the timing of blood collection had no effect on tryptase and DAO levels. While moderately elevated tryptase levels are common in post mortem sera, values above 45 μg/l may support the diagnosis of fatal anaphylaxis. Strongly elevated histamine levels might give an additional clue on fatal anaphylaxis, whereas DAO does not seem to be helpful., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Peptide-based therapies are showing increasing potential for the development of vaccines and in the treatment of many important diseases. We previously reported two peptide conjugate vaccines that protected mice against pneumococcal disease. During this study, we observed an unexpected phenomenon; several vaccine candidates induced a rapid, fatal anaphylaxis after booster injection of the peptide conjugate. Further investigation indicated the reaction was mediated by the production of peptide-specific IgE and the release of histamine. Notably, among seven peptides tested, all of which bound the same mAb that selected them from a phage library, only four elicited this severe reaction. Sequence alignment analysis of all peptides revealed unique clusters of acidic amino acid residues in the allergenic peptides. Substitution of the acidic amino acid residues, ED, of peptide MP2 with their amine equivalents, QN, eliminated the anaphylactic effects but did not affect the production of peptide-specific IgG. These results have important implications for both the study of allergens and the development of future peptide-based therapies.

Subcutaneous allergen immunotherapy (SCIT) has been practiced for 100 years. Many trials have established the efficacy of SCIT in reducing symptoms of both seasonal allergic rhinitis and asthma due to aeroallergens. However, clinical benefits of SCIT are tempered by risks of injection-related systemic reactions and life-threatening anaphylaxis. This article reviews data derived from retrospective surveys conducted to define the incidence, prevalence, and factors contributing to injection-related fatal anaphylactic and near-fatal systemic reactions, as well as recently initiated longitudinal surveillance studies of SCIT reactions., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: To explore the characteristics of autopsy cases of anaphylactic shock induced by cephalosporins and provide the evidences in forensic medicine., Methods: Twenty cases of anaphylactic shock induced by cephalosporins were collected from April 2005 to August 2009 in judicial expertise center of China Medical University, and the characteristics of the cases were analyzed retrospectively., Results: The age of decedents ranged from 40 to 60 years. Ninety percent of cases were from local medical centers and private clinics. The symptoms of the shock appeared 30 s-150 min after the administration of the drug, and death occurred 10 min-210 min after the appearance of the shock symptoms. In all cases, various degrees of eosinophil infiltration were observed in trachea and the lungs. Serum IgE detected by ELISA method was normal value in 14 cases., Conclusion: In fatal anaphylactic cases, little specific findings are detected during postmortem and microscope examination. For this reason, the determination of cause of death in these cases requires comprehensive analysis combined with clinic information and excludes other diseases leading to the sudden death.

The recent health care changes and approval of a generic low-molecular-weight heparin (LMWH) by the US Food and Drug Administration (FDA) merit a review of the facts regarding the new and generic anticoagulants. Fatal hypotension from anaphylactoid type reactions following heparin administration was responsible for more than 149 deaths all over the world. Researchers detected a heparin-like semisynthetic contaminant, over-sulfated chondroitin sulfate (OSCS), that appeared to be intentional. Low-molecular-weight heparins are produced using unfractionated heparin and OSCS has been found in various batches of LMWHs. Some newer anticoagulants are claiming to be free from the need to monitor for therapeutic effect and bleeding risk. Therefore, monitoring assays are not being developed and there is no antidote to reverse bleeding. In addition, there are concerns about reproducibility, product variation, and quality. In conclusion, although the generic LMWHs and newer anticoagulants may appear to be effective for qualified indications, their safety remains to be a concern.

Ab-mediated blockade of the adhesion molecule VLA-4 has been shown to ameliorate disease in human multiple sclerosis patients and experimental autoimmune encephalomyelitis (EAE) animal models. We wanted to determine whether anti-VLA-4 Ab treatment affected the function and persistence of autoreactive T cells in mice with EAE. Unexpectedly, we observed a high level of mortality in anti-VLA-4 mAb (PS/2)-treated mice with actively induced EAE despite decreased disease severity. Investigation of the underlying mechanism showed that injection of PS/2 mAb in combination with pertussis toxin resulted in anaphylaxis and mortality. Furthermore, the data showed that CD4(+) T cells were required for this effect and suggested a role for IL-1β and TNF-α in the underlying pathology. The results reveal a previously not appreciated deleterious effect of anti-VLA-4 Ab treatment in combination with exposure to pertussis toxin.

Controversy exists about the safety of the parenteral iron dextran products, Dexferrum and INFeD, which have been associated with rare, serious anaphylactic-type reactions. In the United States, their product labels carry boxed warnings of this adverse event; some have called for the withdrawal from marketing of the higher molecular weight Dexferrum. Between 2002 and 2007, sales of Dexferrum, INFeD, and iron gluconate Ferrlecit declined 32.5%, 21%, and 4.8%, respectively, while sales of iron sucrose Venofer increased 160%. Voluntary reports submitted to the Food and Drug Administration show anaphylactic reactions and symptoms for the four parenteral iron products. Because of underreporting, possible differential reporting, absence of iron dextran brand names, and incomplete use (denominator) data, incidence rates and relative risk estimates cannot be calculated. U.S. death certificate data show that for most years from 1979 through 2006, no more than 3 deaths per year were coded to "adverse events in therapeutic use of iron preparations;" brand names were not consistently recorded. Emergency department data show small numbers of visits for treatment of allergic reactions with intravenous iron preparations. The data presented herein show that allergic reactions are possible with all four parenteral iron products, and it is difficult to determine which product has the largest risk based on sales data, voluntarily submitted adverse event reports, death certificates, ED visits, and observational studies performed to date. To help differentiate risk among the parenteral iron products, the brand name of the product always should be provided on medical records, death certificates, and adverse drug reaction reports., (Published 2010 Wiley-Liss, Inc.)

To address complications of pathogenic antibody or life-threatening anaphylactic reactions in protein replacement therapy for patients with hemophilia or other inherited protein deficiencies, we have developed a prophylactic protocol using a murine hemophilia B model. Oral delivery of coagulation factor IX fused with cholera toxin beta-subunit (with or without a furin cleavage site; CTB-FFIX or CTB-FIX), expressed in chloroplasts (up to 3.8% soluble protein or 0.4 mg/g leaf tissue), bioencapsulated in plant cells, effectively blocked formation of inhibitory antibodies (undetectable or up to 100-fold less than controls). Moreover, this treatment eliminated fatal anaphylactic reactions that occurred after four to six exposures to intravenous F.IX. Whereas only 20-25% of control animals survived after six to eight F.IX doses, 90-93% of F.IX-fed mice survived 12 injections without signs of allergy or anaphylaxis. Immunostaining confirmed delivery of F.IX to Peyer's patches in the ileum. Within 2-5 h, feeding of CTB-FFIX additionally resulted in systemic delivery of F.IX antigen. This high-responder strain of hemophilia B mice represents a new animal model to study anaphylactic reactions. The protocol was effective over a range of oral antigen doses (equivalent to 5-80 microg recombinant F.IX/kg), and controlled inhibitor formation and anaphylaxis long-term, up to 7 months (approximately 40% life span of this mouse strain). Oral antigen administration caused a deviant immune response that suppressed formation of IgE and inhibitory antibodies. This cost-effective and efficient approach of antigen delivery to the gut should be applicable to several genetic diseases that are prone to pathogenic antibody responses during treatment.

Aims: To determine the frequency of anaphylactic deaths at autopsies performed in Turkey between January 2001 and June 2006 and to review the circumstances of death and autopsy findings., Methods: The Council of Forensic Medicine database in Istanbul was searched for anaphylactic deaths. Postmortem reports and medical records were reviewed to determine the circumstances of death. Data about basic demographics, medical history, drugs responsible for allergic reactions, and pathologic findings at autopsy were collected., Results: A total of 36 anaphylactic deaths from drugs were identified for the study period. Death was due to antibiotics in 26 cases, analgesics in 7 cases, an intraoperative drug in 1 case, an H2 receptor in 1 case, and intravenous contrast medium in 1 case. Out of 36 cases, 19 were male and 17 female. They were aged between 1 and 74 years with the median age of 26.7 years. Death occurred within 1 hour of the onset of anaphylaxis in 27 cases. Findings at autopsy included nonspecific pulmonary edema and congestion, upper airway edema, cerebral hypoxia, and cutaneous edema. Serum tryptase levels were not measured in all cases., Conclusion: Anaphylactic reaction is an uncommon cause of sudden death. In many cases, no specific macroscopic or microscopic findings were detected at autopsy. When serum tryptase levels cannot be determined, in the presence of typical clinical records, eye witness reports and autopsy findings can be useful diagnostic aids.

Reports describing severe allergic shock and fatality following treatment of a common cold or upper respiratory tract infection (URTI) with a Chinese herbal injection were collected. Our analysis of the risks associated with this treatment suggested that the potential risk of serious, or even lethal, anaphylaxis should preclude its use in treating common colds and URTIs. In light of our findings herein, we propose the following five suggestions for improving the clinical safety of delivering Chinese herbal injections as medical treatments. First, Chinese herbal injections should not be delivered in the clinic to treat patients in accordance with Bian zheng lun zhi (broad-spectrum application based on holistic Traditional Chinese Medicine (TCM) theory and methodology), but rather they should be administered to target specific indicated disease processes. Second, Chinese herbal injection indications should be based on the results of double-blind randomized controlled clinical trials. Third, Chinese herbal injections should be used only in cases involving severe disease or to rescue patients in critical condition; they should not be used to treat mild, relatively innocuous diseases, such as common colds and upper respiratory tract infections, given the risk of doing harm. Fourth, Chinese herbal injection formulas should include materials from only a single or a small number of plant sources in known quantities. Fifth, more studies examining the toxicology and allergenic potential of Chinese herbal injections are needed.

Background: One of the main reasons for hospital admission once a child has been stabilized following anaphylaxis is to monitor for a biphasic reaction. However, only a small percentage of anaphylactic episodes involve biphasic reactions that would benefit from admission. Identification of predictive factors for a biphasic reaction would assist in determining who may benefit from prolonged observation., Objective: To determine predictive factors for biphasic reactions in children presenting with anaphylaxis., Methods: This was a retrospective study of children presenting with anaphylaxis to a major paediatric emergency department over a 5-year period., Results: There were 95 uniphasic (87%), 12 (11%) biphasic and two protracted reactions (2%). One child with a protracted reaction died. For the management of the primary anaphylactic reaction, children developing biphasic reactions were more likely to have received >1 dose of adrenaline (58% vs. 22%, P=0.01) and/or a fluid bolus (42% vs. 8%, P=0.01) than those experiencing uniphasic reactions. The absence of either factor was strongly predictive of the absence of a biphasic reaction (negative predictive value 99%), but the presence of either factor was poorly predictive of a biphasic reaction (positive predictive value of 32%). All biphasic reactors, in which the second phase was anaphylactic, received either >1 dose of adrenaline and/or a fluid bolus., Conclusions: Children who received >1 dose of adrenaline and/or a fluid bolus for treatment of their primary anaphylactic reaction were at increased risk of developing a biphasic reaction.

Background: Most studies of anaphylaxis in the community focus on persons at risk who might, or might not, have experienced anaphylaxis., Objective: We sought to focus on survivors of anaphylaxis in the community and their experiences in using, or not using, an epinephrine autoinjector for first-aid treatment., Methods: An e-mail survey was conducted. Responses were anonymous and could not be traced to any person or location. Anaphylaxis was defined as the most severe sudden-onset allergic reaction ever experienced by the participants or a person for whom they were responsible (eg, a child). There were 17 core multiple-choice questions for all participants, with 16 additional questions for users who injected epinephrine either into themselves or someone else, and 1 additional question for nonusers., Results: Of the 1885 participants, 500 (27%) were epinephrine users, and 1385 (73%) were nonusers. The groups were similar with regard to multisystem organ involvement (82% vs 78%, P = .07) and many other aspects of anaphylaxis; however, epinephrine users were more likely (all P < .05) to report respiratory or shock symptoms; to report peanut, fish, or insect sting triggers; to be asthmatic; and to have taken or been given asthma medication on the day of the episode. Epinephrine users reported problems in deciding whether to give the injection, repeat the dose, and/or go to an emergency department. Nonusers reported not injecting epinephrine for various reasons, including use of an H(1)-antihistamine (38%), no prescription for epinephrine (28%), and/or a mild anaphylaxis episode (13%)., Conclusions: In a unique population composed of 1885 survivors of anaphylaxis in the community, users of epinephrine autoinjectors for first-aid treatment were outnumbered by nonusers. The insights reported by epinephrine users and the reasons why nonusers did not inject epinephrine are documented.

Anaphylaxis is a life threatening allergic reaction that is rapid in onset and may cause sudden death. A retrospective study was performed using the database from the Office of the Chief Medical Examiner (OCME) in the State of Maryland and the Department of Forensic Medicine in Shanghai Medical College (DFM-SMC) to examine the etiology and forensic investigation findings of anaphylactic deaths from 2004 to 2006. Details of the medical history, agent responsible for the allergic reaction, death scene investigation and postmortem examination findings were reviewed for all cases. A total of 28 cases of anaphylactic death were identified for the study period, 17 from Maryland and 11 from Shanghai. Of the 17 Maryland cases, 6 (35%) involved allergic reaction to food, 5 (25%) to drugs, 2 to bee stings, 1 to hair dye, and 3 to unknown allergens. Investigation revealed that 9 of 17 cases had a history of asthma and 8 had previous allergic reactions to certain foods and / or drugs. In Shanghai, all 11 deaths resulted from anaphylactic reaction to antibiotics, 10 of which occurred in clinics illegally operated by unlicensed physicians. The interval between the onset of symptoms and death ranged from less than 1 min to 3 days after initially contacting the allergen. In the majority (68%) of cases, death occurred within 8h after the onset of symptoms. Postmortem findings were relatively non-specific, and included pharyngeal/laryngeal edema 14/28 (50%), mucus plugging in the airways 11/28 (39%), and pulmonary congestion and edema 28/28 (100%). Serum tryptase concentrations were measured in 14 cases in Maryland and the concentration ranged from 3.3 ng/ml to 200 ng/ml. There were significant differences with regards to allergen type and the circumstances of death between these two regions. Inappropriate use of antibiotics and illegal medical practices were the main causes of identified anaphylactic death in Shanghai. In Maryland anaphylactic deaths were mainly caused by food reactions. This study indicates that the postmortem diagnosis of anaphylactic death is usually based on exclusion and circumstantial evidence. Knowledge of the patient's history and circumstances of death is of major importance for the forensic pathologist when investigating suspected anaphylactic death.

Background: Detailed data on fatal anaphylaxis are limited, with national anaphylaxis fatality data for the United Kingdom and food-induced anaphylaxis fatality data for the United States. Time trends for anaphylaxis fatalities are not available., Objective: We examined causes, demographics, and time trends for anaphylaxis fatalities in Australia between January 1997 and December 2005 and compared these with findings for anaphylaxis admissions., Methods: Data on anaphylaxis deaths and hospital admissions were extracted from a national database. Death certificate codes were analyzed to determine the likely cause and associated comorbidities., Results: There were 112 anaphylaxis fatalities in Australia over 9 years. Causes were as follows: food, 7 (6%); drugs, 22 (20%); probable drugs, 42 (38%); insect stings, 20 (18%); undetermined, 15 (13%); and other, 6 (5%). All food-induced anaphylaxis fatalities occurred between 8 and 35 years of age with female preponderance, despite the majority of food-induced anaphylaxis admissions occurring in children less than 5 years of age. Most insect sting-induced anaphylaxis deaths occurred between 35 and 84 years almost exclusively in male subjects, although bee sting-induced admissions peak between 5 and 9 years of age with a male/female ratio of 2.7. However, most drug-induced anaphylaxis deaths occurred between 55 and 85 years with equal sex distribution similar to drug-induced anaphylaxis admissions. There was no evidence of an increase in death rates for food-induced anaphylaxis, despite food-induced anaphylaxis admissions increasing approximately 350%. In contrast, drug-induced anaphylaxis deaths increased approximately 300% compared with an approximately 150% increase in drug-induced anaphylaxis admissions., Conclusion: The demographics for anaphylaxis deaths are different to those for anaphylaxis presentations. Anaphylaxis mortality rates remain low and stable, despite increasing anaphylaxis prevalence, with the exception of drug-induced anaphylaxis deaths, which have increased.

Introduction: Paracetamol (acetaminophen) is one of the most common agents deliberately ingested in self-poisoning episodes and a leading cause of acute liver failure in the western world. Acetylcysteine is widely acknowledged as the antidote of choice for paracetamol poisoning, but its use is not without risk. Adverse reactions, often leading to treatment delay, are frequently associated with both intravenous and oral acetylcysteine and are a common source of concern among treating physicians., Methods: A systematic literature review investigating the incidence, clinical features, and mechanisms of adverse effects associated with acetylcysteine., Results: A variety of adverse reactions to acetylcysteine have been described ranging from nausea to death, most of the latter due to incorrect dosing. The pattern of reactions differs with oral and intravenous dosing, but reported frequency is at least as high with oral as intravenous. The reactions to the intravenous preparation result in similar clinical features to true anaphylaxis, including rash, pruritus, angioedema, bronchospasm, and rarely hypotension, but are caused by nonimmunological mechanisms. The precise nature of this reaction remains unclear. Histamine now seems to be an important mediator of the response, and there is evidence of variability in patient susceptibility, with females, and those with a history of asthma or atopy are particularly susceptible. Quantity of paracetamol ingestion, measured through serum paracetamol concentration, is also important as higher paracetamol concentrations protect patients against anaphylactoid effects. Most anaphylactoid reactions occur at the start of acetylcysteine treatment when concentrations are highest. Acetylcysteine also affects clotting factor activity, and this affects the interpretation of minor disturbances in the International Normalized Ratio in the context of paracetamol overdose., Conclusion: This review discusses the incidence, clinical features, underlying pathophysiological mechanisms, and treatment of adverse reactions to acetylcysteine and identifies particular "at-risk" patient groups. Given the commonality of adverse reactions associated with acetylcysteine, it is important to ensure that any adverse event does not preclude patients from receiving maximal hepatic protection, particularly in the context of significant paracetamol ingestion. Further work on mechanisms should allow specific therapies to be developed.

Although the acute death syndrome in feline heartworm disease is widely recognized, its pathogenesis remains a mystery. The most widely held hypothesis is that an acute anaphylactic reaction, perhaps precipitated by the death of the parasite, is the underlying cause. This study investigated the role of the physical form of antigen (Ag) in the ensuing reaction when Dirofilaria immitis-sensitized cats are challenged by intravenous (IV) administration of heartworm Ag. Healthy D. immitis-naive cats (n = 23) were sensitized using subcutaneous injections of adjuvanted D. immitis Ag administered weekly for 6 weeks. After sensitization, cats (n = 20) were anaesthetized and challenged with IV D. immitis Ag in various forms or with IV sterile 0.9% saline (n = 3). Systolic blood pressure, respiratory rate, degree of dyspnea, blood oxygen saturation, and heart rate were measured immediately before and at 10-15 min intervals after challenge until terminal apnea occurred or until euthanasia at 140 min after challenge. Blood samples were collected for complete blood count and measurements of serum serotonin immediately before and at 10, 20, and 35 min after challenge. Clinical observations were recorded as they occurred, or at 10-15 minute intervals, whichever was the more frequent. The most severe post-challenge reactions occurred in cats challenged with Ag from dead worms, live worms, and 20 ng/mL Ag. Dyspnea increased significantly after challenge in all three groups (p < 0.001; p = 0.04, and p = 0.002, respectively), and blood oxygen saturation dropped post-challenge in the Dead Worm (p < 0.001) and the 20 ng/mL Ag (p = 0.002) groups. In the 20 ng/mL Ag group, systolic blood pressure decreased (p <0.05) and respiratory rate increased (p < 0.05) post-challenge. Clinical observations included dyspnea, gastrointestinal signs (retching, defecation, or flatulence), urination, and less commonly, hemorrhage from the nostrils or anus, or cutaneous swelling (general or specifically facial). The 20 ng/mL Ag group had the highest rate of clinical signs, followed by the Dead Worm group. The most common and reliable hematologic change associated with severe clinical effects of D. immitis Ag challenge was increased hematocrit, which was statistically higher after challenge than at baseline in the Dead Worm group (p = 0.012). The model demonstrated that the physical form of heartworm Ag used for IV challenge in D. immitis-sensitized cats is an important factor for determining the characteristics of the post-challenge reaction, and the amount of exposed internal filarial Ag presented to the feline immune system may influence the severity of the response to challenge.

Among solid organs, transfer of peanut allergy from donor to recipient has been implicated after liver transplantation. We report the first case in which such transfer occurred after a lung transplant. A 42-year-old woman with history of sarcoidosis underwent a successful bilateral lung transplant from a donor who died from anaphylactic shock after eating peanut-related food. Seven months later, she ate a peanut butter cookie at a transplant support group meeting. Immediately thereafter, she developed an anaphylactic reaction, but survived with prompt treatment. During subsequent follow-up, she could recall three prior episodes of wheezing and difficulty breathing after eating peanut-related foods. The first episode occurred 4 days after the transplant. Prior to her transplant, she never had problems eating peanuts. Skin-prick testing confirmed peanut sensitization. She avoided peanuts and, although her skin-prick test became negative, she still manifested peanut allergy when formally challenged orally with the food. She was advised to continue abstaining from all peanut-related foods. This case emphasizes the importance of considering donor allergy transfer when caring for all solid-organ transplant recipients in order to avoid a life-threatening event.

Selective ewe's or goat's milk allergy without cow's milk allergy often presents as a severe picture. Diagnosis and follow-up are facilitated by the use of laboratory tests. Serum tryptase is elevated after mast cell degranulation. Combined determination of serum tryptase and immunoglobulin-E levels are particularly useful in the work-up of anaphylaxis, should it have been fatal. A case of ewe's milk allergy without cow's milk allergy and its laboratory work-up are reported.

Background: Previous US population-based epidemiologic studies of anaphylactic deaths have been limited by small populations and/or few deaths. The objective of this study was to determine the 10-year incidence of death from anaphylaxis in Florida and its descriptive epidemiology., Methods: Patients who died from anaphylaxis from 1996 to 2005 were identified from ICD-9 and ICD-10 codes on death certificates statewide. Age, race and gender-specific anaphylactic death rates were calculated., Results: There were 89 deaths among Florida residents. The individuals with autopsy confirmed diagnoses, and those with clinical diagnoses only, did not differ with regard to race, anaphylactic triggers or the clinical variables of lung and heart disease. Annual death rate for anaphylaxis in Florida was 5.02/10 000 000. The relative risk of death from anaphylaxis was 14.09 for individuals > or =65 years old (P = 0.0000002) and 6.38 for individuals 35-64 years old (P = 0.0019) compared with those who were 5-14 years of age. Deaths among Florida residents that occurred in emergency rooms or outpatient settings were 2.11 times as likely to be anaphylactic deaths than deaths that occurred in inpatient settings (P = 0.0026). The ratios of anaphylactic deaths to total deaths in March and April and in July and August were greater than the ratios for the other bimonthly periods (P = 0.02)., Conclusion: Death from anaphylaxis in Florida was more likely to occur in older individuals, in an emergency department, and in the months of March and April and July and August.

In this issue of Immunity, Tsujimura et al. (2008) report that the release of platelet-activating factor by basophils stimulated with immunoglobulin G1 (IgG1)-antigen immune complexes contributes substantially to the expression of an IgG1-dependent alternative pathway of systemic anaphylaxis in mice.

Background: Platelet-activating factor (PAF) is an important mediator of anaphylaxis in animals, and interventions that block PAF prevent fatal anaphylaxis. The roles of PAF and PAF acetylhydrolase, the enzyme that inactivates PAF, in anaphylaxis in humans have not been reported., Methods: We measured serum PAF levels and PAF acetylhydrolase activity in 41 patients with anaphylaxis and in 23 control patients. Serum PAF acetylhydrolase activity was also measured in 9 patients with peanut allergy who had fatal anaphylaxis and compared with that in 26 nonallergic pediatric control patients, 49 nonallergic adult control patients, 63 children with mild peanut allergy, 24 patients with nonfatal anaphylaxis, 10 children who died of nonanaphylactic causes, 15 children with life-threatening asthma, and 19 children with non-life-threatening asthma., Results: Mean (+/-SD) serum PAF levels were significantly higher in patients with anaphylaxis (805+/-595 pg per milliliter) than in patients in the control groups (127+/-104 pg per milliliter, P<0.001 after log transformation) and were correlated with the severity of anaphylaxis. The proportion of subjects with elevated PAF levels increased from 4% in the control groups to 20% in the group with grade 1 anaphylaxis, 71% in the group with grade 2 anaphylaxis, and 100% in the group with grade 3 anaphylaxis (P<0.001). There was an inverse correlation between PAF levels and PAF acetylhydrolase activity (P<0.001). The proportion of patients with low PAF acetylhydrolase values increased with the severity of anaphylaxis (P<0.001 for all comparisons). Serum PAF acetylhydrolase activity was significantly lower in patients with fatal peanut anaphylaxis than in control patients (P values <0.001 for all comparisons)., Conclusions: Serum PAF levels were directly correlated and serum PAF acetylhydrolase activity was inversely correlated with the severity of anaphylaxis. PAF acetylhydrolase activity was significantly lower in patients with fatal anaphylactic reactions to peanuts than in patients in any of the control groups. Failure of PAF acetylhydrolase to inactivate PAF may contribute to the severity of anaphylaxis., (Copyright 2008 Massachusetts Medical Society.)

Relatively little is known about the characteristics of patients who visit the emergency department for acute allergic reaction. The earliest symptoms are swelling of tissues, sweating, restlessness, itching, nausea, vomiting, diarrhoea, coughing or wheezing. Hypotension, circulatory failure and cardiac arrest may occur suddenly, often associated with bronchial spasm or laryngeal oedema. The objective of this review is to describe the child with severe acute allergic reaction in emergency department.

Background: Recent investigations in developed countries have found marked increases in the prevalence of allergic conditions., Objective: We sought to examine recent time trends in the prevalence of anaphylaxis, angioedema, and urticaria by describing trends and age and sex differentials in hospitalizations for these conditions in Australia., Methods: Data on hospital admissions and deaths for anaphylaxis, angioedema, and urticaria were extracted for the periods 1993-1994 to 2004-2005 and 1997-2004, respectively. For hospital admissions, age-standardized rates were calculated. Time trends and sex differences were quantified by using negative binomial models., Results: During the study period, there was a continuous increase in the rate of hospital admissions for angioedema (3.0% per year), urticaria (5.7% per year), and, most notably, anaphylaxis (8.8% per year). There was a particularly steep increase in the incidence of hospitalization for food-related anaphylaxis among children aged less than 5 years. Admissions for non-food-related anaphylaxis occurred predominantly in adults, particularly those more than 35 years of age. Among children, admission rates were higher in boys, but the sex difference was reversed among adults. Over an 8-year period, there were 106 deaths associated with anaphylaxis or angioedema., Conclusion: Hospitalization rates for allergic conditions are on the increase, but the nature and causative factors differ between adults and children. The relation of these changes to those in the prevalence of specific allergen sensitization in the community requires further investigation in population studies., Clinical Implications: Among older persons, angioedema is becoming an increasing problem. Among children, hospitalization because of food-induced anaphylaxis is a growing concern.

Background: Epinephrine and more recently arginine vasopressin (AVP) alone or in combination have been proposed in patients with anaphylactic shock, but few experimental data exist. The authors investigated the effects of epinephrine only, AVP only, or epinephrine followed by AVP in a model of anaphylactic shock., Methods: Ovalbumin-sensitized Brown Norway rats were anesthetized, intubated, and shock induced with ovalbumin. Rats (n = 6/group) were randomly allocated to receive 5 min after shock onset: (1) saline (no-treatment group); (2) two boluses of epinephrine followed by continuous infusion (epinephrine group); (3) AVP bolus followed by continuous infusion (AVP group); (4) epinephrine bolus followed by AVP continuous infusion (epinephrine + AVP group). Mean arterial pressure (MAP) and skeletal muscle oxygen pressure (PtiO2) were measured. Continuous infusion rates were titrated to reach MAP values of 60 mmHg. Survival was analyzed., Results: Without treatment, MAP and PtiO2 decreased rapidly with 0% survival. In the epinephrine group, MAP and PtiO2 recovered after an initial decrease, with 84% survival. In the AVP group, MAP was partially restored and subsequently decreased; PtiO2 values decreased to values similar to those in the no-treatment group; survival was 0%. In the epinephrine + AVP group, MAP and PtiO2 values increased more slowly as compared with the epinephrine group; survival was 100%., Conclusions: In this model of anaphylactic shock, early treatment with epinephrine followed by continuous epinephrine or vasopressin infusion resulted in an excellent survival rate, whereas vasopressin only resulted in a 100% death rate. These experimental results suggest that epinephrine must still be considered as the first-line drug to treat anaphylactic shock.

Background: Anaphylaxis is an infrequent cause of sudden death. Death often results from circulatory collapse, respiratory arrest, or both., Objective: To investigate the causes of death, anatomical findings, and comorbid diseases in cases of fatal anaphylaxis., Methods: This is a retrospective case review of 25 unselected cases of documented fatal anaphylaxis. Each case report contained details of the fatal reaction, a review of the medical record, and laboratory and autopsy findings. Serum tryptase concentrations were measured in 7 cases., Results: The anaphylactic deaths included 7 reactions to medications, 6 to radiocontrast material, 6 to Hymenoptera stings, and 4 to foods. The mean age was 59 years. The anaphylactic reaction began within 30 minutes of exposure in 21 of 25 cases, with death occurring within 60 minutes in 13 of 25 cases. Urticaria occurred in only 1 of 25 cases. Anatomical findings consistent with anaphylaxis were present in 18 of 23 patients undergoing autopsy. At least 1 significant comorbid disease was identified in 22 of 25 cases., Conclusions: (1) Elderly patients with substantial comorbid conditions constituted a significant number of the anaphylactic fatalities; (2) the onset of severe anaphylaxis occurred in less than 30 minutes in nearly every case; (3) 18 of 23 cases were associated with specific anatomical findings of anaphylaxis; (4) self-administered epinephrine was used in just 1 of 5 cases; and (5) serum total tryptase concentrations were elevated markedly in 4 of 7 cases tested.

Goals: The most well-known adverse events of oxaliplatin are hematologic toxicity, gastrointestinal tract toxicity, and sensory neuropathy. However, hypersensitivity reaction of oxaliplatin, especially severe anaphylactic reactions (SAR), was less often reported., Materials and Methods: Three hundred and three patients with colon cancer treated by oxaliplatin-containing chemotherapy in one institution were analyzed. Patients were considered to have oxaliplatin-induced SAR if they suffered from at least one of the following symptoms after oxaliplatin infusion: symptomatic bronchospasm, allergy-related edema/angioedema, unstable blood pressure, or anaphylaxis. The reported cases in published literatures that met our definition were also reviewed., Result: There were 4 out of 303 patients suffering from SAR after receiving oxaliplatin infusion, with an estimated incidence of 1.32%. Two of them became unconscious and had hypertensive crisis, and one patient had consciousness loss with hypotension. All four patients needed various level of oxygen support. Twenty-seven cases of oxaliplatin-induced SAR were found from Medline. Among the 31 reported cases, the most frequent SAR symptom was hypotension. However, we reported two unique SAR cases with hypertension crisis. In only four out of ten cases, patients could tolerate rechallenge of oxaliplatin. There is no association between the occurrence of oxaliplatin-induced SAR and metastatic sites., Conclusion: Oxaliplatin-induced SAR is a rare but potentially fatal complication. Hypertension crisis can be one of the oxaliplatin anaphylactic reactions. Only few patients suffering this complication could tolerate subsequent treatment of oxaliplatin by prolonged infusion time or using a desensitization schedule, thus changing regimen might be a better alternative for them.

27 autopsy cases died of anaphylactic shock induced by mainline during 1996-2005 were selected and analyzed. The results showed that most anaphylactic shock induced by mainline were rapid type and more easily happened in individual clinique and lawless clinique, and it could be arisen by either antibiotics or non-antibiotics. In some cases, there may be no pathologic findings by autopsy. So, all the materials must be taken into account for determination the anaphylactic shock, such as drugs, clinic symptom, autopsy findings, and so on.

Aims: To determine the frequency of anaphylactic deaths amongst coronial autopsy cases performed in the greater Auckland region from 1985 to 2005, and review the circumstances of death and autopsy findings., Methods: A computerised search for anaphylactic deaths was performed using the Forensic Pathology Department database at Auckland City Hospital. Postmortem reports and police reports were reviewed to determine the circumstances of death. Details recorded included basic demographic data, medical history, agent responsible for the allergic reaction, and pathologic findings at autopsy., Results: A total of 18 cases of anaphylactic deaths were identified for the study period, including nine males and nine females, age range 33-76 years, mean 51.9 years. There were 10 reactions to drugs or contrast media (4 anaesthetic agents, 3 antibiotic, 2 IV contrast media, 1 streptokinase), four to bee/wasp venom, two to seafood, and two undetermined. Death occurred within 1 hour of onset of anaphylaxis in 12 cases. Findings at autopsy included non-specific pulmonary oedema and congestion (n = 13), laryngeal oedema (n = 5), cerebral hypoxia (n = 4) and cutaneous oedema (n = 1). Serum tryptase levels were measured in 15 cases, and were significantly elevated (>20 microg/L) in eight cases., Conclusion: Anaphylactic reaction is an uncommon cause of sudden death. In many cases, no specific macroscopic or microscopic findings were detected at autopsy. In the presence of a typical clinical history, postmortem measurement of serum tryptase levels can be a useful diagnostic aid.

Cases of life-threatening and fatal anaphylaxis represent the most extreme forms of acute allergic reactions. They are estimated to have an incidence of 1-3 per 10,000 persons, with an associated death rate of 0.5-2%. Medicinal drugs, insect stings and foods are the most common triggering agents. In particular in the case of drugs, the median time lapse between contact with the triggering agent and death is a very short 5-10 minutes. Fatal anaphylaxis due to foods usually leads first to dyspnea and then to respiratory failure. Allergic bronchial asthma represents a major risk factor. Knowledge of the allergens capable of triggering life-threatening and fatal anaphylaxis makes it easier for the physician to assess the risk potential when confronted by an emergency situation.

Objectives: To determine the mortality and clinical features of patients presenting with severe hypotension in the pre-hospital phase of care., Design: A prospective observational study. The medical records of patients attended by a physician-led pre-hospital medical service were examined prospectively. Inclusion criteria were severe shock characterized by a non-palpable radial pulse and unrecordable blood pressure at clinical presentation. All consecutive records between September 2002 and September 2003 were included., Setting: Seine Saint-Denis, an urban area with a population of 1.5 million located in the northern suburbs of Paris, France., Interventions: None., Results: One hundred and thirty one patients met the inclusion criteria. The overall mortality was 50% (66/131). Of the deaths, 20% (13/66) occurred in the pre-hospital phase and 80% (53/66) after arrival in hospital. Clinical features significantly associated with increased mortality were: more than one pre-existing co-morbidity, increased age, high Knaus score, a low Glasgow Coma Score, vasopressor administration, pre-hospital cardiac arrest and hypotension on arrival at hospital. The presence of anaphylactic shock was associated with low mortality. In multivariate analysis, occurrence of cardiac arrest (OR=13.5 [2.8; 64.5]), age (OR=1.03 [1.01; 1.05]) and low Glasgow Coma Scale score value (OR=1.15 [1.05; 1.29]) were independently associated with mortality., Conclusion: Patients presenting with profound hypotension in the pre-hospital phase have a high mortality. Patients who recover their blood pressure with interventions before hospital admission and those with anaphylactic shock have a better outcome than other patient sub-groups.

Objective: This study aims to understand the pathophysiology of anaphylaxis in Dirofilaria immitis-sensitised cats by analysing objective physiological and haematological measurements after challenge., Design: Nineteen healthy D immitis-naive cats were sensitised using weekly injections of aluminium hydroxide-adjuvanted D immitis antigen, administered subcutaneously over 6 weeks. After sensitisation, cats (n = 16) were anaesthetised and challenged with intravenous D immitis antigen. A control group (n = 3) was sham-challenged using intravenous sterile 0.9% saline. Systolic blood pressure (measured non-invasively/indirectly), respiratory rate, degree of dyspnoea, blood O2 saturation, expired CO2, and heart rate and were measured immediately before and at 10 to 15 min intervals after challenge until terminal apnoea occurred or euthanasia at 140 mins post-challenge. Blood was collected for complete blood count immediately before and at 10, 20 and 35 mins after challenge. Clinical observations were recorded as they occurred., Results: Antigen-challenged cats were divided into two groups: acute (apnoea occurred within 25 mins of challenge) and subacute (breathing at 25 mins after challenge). In both groups, the degree of dyspnoea increased and blood O2 saturation and blood pressure decreased. Respiratory rate increased in the subacute group. Expired CO2 decreased in both Ag-challenged and control groups. Haematocrit increased in the subacute group. Neutrophil count decreased in the acute group and platelet count decreased in the subacute group. Eosinophil count decreased in the subacute and control groups. Sustained dyspnoea and gastrointestinal signs were the most common clinical manifestations of anaphylaxis in the antigen-challenged cats., Conclusions: Intravenous challenge with D immitis antigen in sensitised cats results in dyspnoea, hypoxaemia and systemic hypotension accompanied by haemoconcentration.

With the advent of developments and advances in hemodialysis machine technology, dialysate water purification, and dialyzers, the clinical spectrum of intradialytic complications has changed over the decades. In the pioneering days of hemodialysis, patients could develop allergic reactions to dialyzer membranes, sterilizing and reprocessing agents, coupled with machines that could not accurately control ultrafiltration rates, and chemically and bacterially contaminated dialysate. Whereas today, although cardiovascular problems remain the most common intradialytic complication, these are mainly due to the time restraints of trying to cope with excessive dialytic weight gains and achieve target dry weight on a thrice weekly schedule, coupled with an aging elderly dialysis population with increasing co-morbidity.

Background: Pediatric asthma is the No. 1 chronic disease in childhood and is responsible for significant morbidity and mortality. In Nebraska, the number of asthma-related deaths is greater than the national average, and in 1998, 2 students died of acute asthma attacks while attending school in the Omaha public schools (OPSs). In response, we designed and implemented a program to respond to this problem., Objective: To implement and study a school-based program for the treatment of life-threatening asthma and anaphylaxis in the OPSs., Methods: The Emergency Response to Life-Threatening Asthma or Systemic Allergic Reactions (Anaphylaxis) Protocol was designed and evaluated in 78 OPSs from 1998 to 2003. Nurses and school staff were trained in the protocol, which required the use of nebulized albuterol and/or intramuscular epinephrine in conjunction with an emergency response procedure. Outcomes were measured by improvement in acute care in schools and survival of students., Results: In the 5 years of evaluation, 98 students were treated successfully. One student died. Of those treated with the protocol, equal numbers had at school both asthma action plans (AAPs) and metered-dose inhalers (MDIs), MDIs only, or neither AAPs nor MDIs. As a result of the program, there has been an increased awareness from parents, teachers, and physicians about the necessity of an emergency response program. In 2002, an outcome of the OPS program resulted in the formation of Attack on Asthma Nebraska to ensure that Nebraska schools have the education, training, and medications to respond to anyone experiencing a life-threatening asthma or anaphylaxis attack at school. The following year, a revised protocol was approved by the Nebraska State Board of Education for use in all Nebraska schools., Conclusions: Emergency response protocols provide protection for children while in school. This program should serve as a national model for other school-based programs for children and adolescents with asthma and anaphylaxis.

Anaphylaxis is a source of anxiety for patients and healthcare providers. It is a medical emergency that presents with a broad array of symptoms and signs, many of which can be deceptively similar to other diseases such as myocardial infarction, asthma, or panic attacks. In addition to these diagnostic challenges, anaphylaxis presents management difficulties due to rapid onset and progression, lack of appropriate self-treatment education and implementation by patients, severity of the allergic response, exacerbating medications or concurrent disease, and unpredictability. The most common causes of anaphylaxis are food allergies, stinging insects and immunotherapy (allergy shots) but idiopathic anaphylaxis, latex allergy and drug hypersensitive all contribute to the epidemiology. Reactions to IVP and other dyes are coined anaphylactoid reactions but have identical pathophysiology and treatment, once the mast cell has been degranulated. As many antigens can be the trigger for fatal anaphylaxis, it is useful to examine the features of each etiology individually, highlighting factors common to all fatal anaphylaxis and some specific to certain etiologies. Generally what distinguishes a fatal from non fatal reaction is often just the rapidity to apply correct therapy. Prevention is clearly the key and should identify high-risk patients in an attempt to minimize the likely of a severe reaction. Although fatal anaphylaxis is rare, it is likely underreported.

The results from the Swedish system for reporting severe and fatal reactions caused by food for the period 1993-96 were published in Lakartidningen in 1997. We now report the results for the period 1997-2003. The number of fatal cases has decreased from 1.75 to 0.86 per year and the number of life-threatening cases from 3 to I per year. The most gratifying result was the large decrease in severe reactions caused by soy, from 3 deaths and 6 life-threatening cases during the first 4-year period to just one life-threatening case during the following 7-year period. This reduction is probably largely due to an increased awareness of identified risk persons, but also to a reduced use of soy protein. The ongoing study illustrates the usefulness of a national system for reporting severe and fatal reactions caused by food.