Onset Of Anaphylaxis Research Articles

Could aluminum be a new hidden allergen in type 1 hypersensitivity reactions when used as a drug additive?

Medications usually contain numerous additives and preservatives. Some of these agents have been reported as causative factors in adverse drug reactions, including asthma attacks, urticaria and/or angioedema, and even severe systemic anaphylaxis. Moreover, allergens such as additives and preservatives may be hidden as they are not easily identified during etiological investigations.

Elevated exhaled nitric oxide in anaphylaxis with respiratory symptoms

BackgroundAnaphylaxis is a serious type I allergic reaction that occurs suddenly and can result in death, but it is sometimes difficult to differentiate from other diseases, and physicians must rely on symptoms alone for its diagnosis. Meanwhile, fractional exhaled nitric oxide (FeNO) concentration, used in assessing airway inflammation in bronchial asthma, is known to be affected by atopic disposition. The possible role of FeNO measurements was evaluated in patients with anaphylaxis. MethodsFeNO was measured in 52 adult patients (17–78 years old, median age 41.5 years) in whom anaphylaxis occurred. These measurements were made within 24 h after onset and after about one month when the patients were symptom-free. In some of these patients, FeNO was measured a third time, two months or more after onset. ResultsThe FeNO level in the 52 patients was not significantly different in measurement made within 24 h of onset of anaphylaxis and after one month. However, excluding 9 patients who also had asthma history, the FeNO level in the remaining 43 patients decreased significantly from within 24 h of onset (36.7 ± 27.5 ppb) to one month later (28.8 ± 19.5 ppb). Of these 43 patients, this phenomenon was evident in a group that had respiratory symptoms (31 patients), but it was not seen in a group that did not have respiratory symptoms (12 patients). ConclusionsElevation of FeNO was related to respiratory symptoms observed in anaphylactic patients without asthma. Although the mechanism of increased FeNO level is unclear, its usefulness for diagnosis of anaphylaxis must be examined in prospective studies.

Pediatric anaphylactic adverse events following immunization in Victoria, Australia from 2007 to 2013

BackgroundAnaphylaxis is a rare life-threatening adverse event following immunization (AEFI). Variability in presentation can make differentiation between anaphylaxis and other AEFI difficult. This study summarizes pediatric anaphylaxis AEFI reported to an Australian state-based passive surveillance system. MethodsAll suspected and reported pediatric (<18 years) anaphylaxis AEFI notified to SAEFVIC (Surveillance of Adverse Events Following Vaccination In the Community) Melbourne, Australia, between May 2007 to May 2013 were analyzed. Clinical descriptions of the AEFI, using the internationally recognized Brighton Collaboration case definition (BCCD) and final outcome were documented. Results93% (25/27) of AEFI classified as anaphylaxis met BCCD criteria, with 36% (9/25), assessed as the highest level of diagnostic certainty (Level 1). Median age was 4.7 years (range 0.3–16.2); 48% of cases were male. The vaccine antigens administered included: diphtheria, tetanus, acellular pertussis (DTaP) alone or in combination vaccines containing other antigens in 11 of 25 cases (44%); and live attenuated measles mumps rubella (MMR) vaccine for six (five also had other vaccines concomitantly administered). The estimated incidence rate of anaphylaxis for DTaP vaccines was 0.36 cases per 100,000 doses, and 1.25 per 100,000 doses for MMR vaccines. The majority of cases had rapid onset, but in 24% (6/25) of cases, first symptoms of anaphylaxis developed ≥30min after immunization. In 60% (15/25) of cases, symptoms resolved ≤60min of presentation. Intramuscular adrenaline was administered in 90% (18/25) of cases. All cases made a full recovery with no sequelae identified. ConclusionThis comprehensive case series of pediatric anaphylaxis as an AEFI identified that diagnostic criteria are useful when applied to a passive vaccine surveillance system when adequate clinical information is available. Anaphylaxis as an AEFI is rare and usually begins within 30min of vaccination. However, healthcare professionals and vaccinees/parents should be aware that onset of anaphylaxis can be delayed beyond 30min following immunization and that medical attention should be sought promptly if anaphylaxis is suspected.

Estrogen increases the severity of anaphylaxis in female mice through enhanced endothelial nitric oxide synthase expression and nitric oxide production

Clinical observations suggest that anaphylaxis is more common in adult women compared with adult men, although the mechanistic basis for this sex bias is not well understood. We sought to document sex-dependent differences in a mouse model of anaphylaxis and explore the role of female sex hormones and the mechanisms responsible. Passive systemic anaphylaxis was induced in female and male mice by using histamine, as well as IgE or IgG receptor aggregation. Anaphylaxis was assessed by monitoring body temperature, release of mast cell mediators and/or hematocrit, and lung weight as a measure of vascular permeability. A combination of ovariectomy, estrogen receptor antagonism, and estrogen administration techniques were used to establish estrogen involvement. Anaphylactic responses were more pronounced in female than male mice. The enhanced severity of anaphylaxis in female mice was eliminated after pretreatment with an estrogen receptor antagonist or ovariectomy but restored after administration of estradiol in ovariectomized mice, demonstrating that the sex-specific differences are due to the female steroid estradiol. Estrogen did not affect mast cell responsiveness or anaphylaxis onset. Instead, it increased tissue expression of endothelial nitric oxide synthase (eNOS). Blockage of NOS activity with the inhibitor L-NG-nitroarginine methyl ester or genetic eNOS deficiency abolished the sex-related differences. Our study defines a contribution of estrogen through its regulation of eNOS expression and nitric oxide production to vascular hyperpermeability and intensified anaphylactic responses in female mice, providing additional mechanistic insights into risk factors and possible implications for clinical management in the further exploration of human anaphylaxis.

Exercise-induced Anaphylaxis: the Role of Cofactors.

Introduction:Anaphylaxis is a dramatic clinical emergency. It is a very severe, life-threatening generalized or systemic hypersensitivity reaction. Based on immunologic mechanism the anaphylaxis is divided in IgE, IgG, complement, or immune complexes-mediated vs non allergic anaphylaxis. There are a lot of etiologic factors of anaphylaxis, but the three principal immunologic triggers are drugs, insect stings, and foods. Regarding the clinical severity there are several proposed grading systems. The diagnosis of anaphylaxis is mainly clinical.Discussion:The anaphylaxis markers measured in clinical laboratories are total tryptase and histamine. There are some conditions that modulate the onset of anaphylaxis, acting as co- or augmentation factors, which significantly lower the allergen dose necessary for triggering anaphylaxis. The well-documented cofactors of anaphylaxis are physical exercise, alcohol consumption, some foods, co-administration of nonsteroidal anti-inflammatory drugs (NSAID), and concomitant infectious diseases. Development of anaphylaxis depends on the sensitization pattern, the proportion of the involved immunoglobulin classes, characteristics of the allergen, the proportion of the involved immunoglobulin classes, the avidity and affinity of immunoglobulins to bind an allergen, the route of allergen application, and, last but not least, the presence of cofactors of anaphylaxis.Conclusion:Anaphylaxis remains a continuous challenge for the diagnosis and treatment. The adequate management of anaphylaxis requires rapid diagnosis, implementation of primary and secondary prevention measures, and immediate administration of subcutaneous epinephrine.

Anaphylactic Shock Decreases Cerebral Blood Flow More Than What Would Be Expected From Severe Arterial Hypotension

To the Editor In a recent issue of Shock (1), a very important paper was published with the title: “Anaphylactic Shock Decreases Cerebral Blood Flow More Than What Would Be Expected From Severe Arterial Hypotension.” The authors of this article concluded that, in anaphylactic shock, severe impairment of the cerebral blood flow takes place, which could not be explained by the level of arterial hypotension. In their experiments with rat model of anaphylaxis, the tissue oxygen partial pressure decreased very rapidly, as early as 1 min following the onset of anaphylaxis, and this was attributed to the early and direct action of anaphylactic mediators on cerebral vessels. Indeed, mast cell mediators such as histamine, chymase, and leukotrienes can induce cerebral artery spasm (2), and platelet-activating factor can reduce cerebral blood flow (3), leading to postischemic hypoperfusion. Therefore, cerebral ischemia and brain injury following anaphylactic shock could be due to direct action of anaphylactic mediators on the cerebral arterial system and not due to arterial hypotension. The above came to support our view on pathophysiology of anaphylactic shock that systemic vasodilatation and plasma and volume loss due to vascular permeability, reduced venous return, reduced cardiac output, and coronary hypoperfusion are not the sole primary cause of tissue damage. Experimental and clinical evidence has shown that, in anaphylactic shock, the coronary arteries could be the primary target of anaphylaxis (4), resulting in the development of Kounis anaphylaxis–associated coronary syndrome (5). In an experiment with ovalbumin-sensitized guinea pigs, which took place more than 20 years ago (6), it was concluded that the registered anaphylactic damage was not due to peripheral vasodilatation, and this can be definitely excluded. This was based on the finding that within 3 min after antigen administration, the left ventricular end-diastolic pressure and arterial blood pressure increased, indicating pump failure. Contemporarily, electrocardiographic recordings uniformly showed signs of acute myocardial ischemia. The blood pressure started declining steadily after 4 min. Today, Dr Stephan Felix (6), the author who performed the above experiments, still believes that, in anaphylactic shock, tissue ischemia is due to disturbances of vasomotion of the coronaries (either coronary vasospasm or disturbances of the microcirculation). However, he cannot exclude fluid extravasation (personal communication, email, November 26, 2012). Other experiments (7), with isolated guinea pig hearts undergoing anaphylaxis following intra-aortic injection of antigen, have shown a prompt and prolonged decrease in coronary blood flow, an abrupt heart rate increase reaching the peak within 2 min, and a transient increase in ventricular contractile force. It has been shown also (8) that anaphylactic cardiac damage is dissociated temporarily into two sets of events: an initial primary coronary reaction caused by intracardiac release of histamine and a subsequent cardiovascular reaction secondary to systemic release of mediators. There are, currently, patients with anaphylactic cardiac shock who did not respond to intravenous fluid administration and antiallergic therapy but required coronary event treatment protocol. In a patient (9) who was stung by multiple wasps and developed type I variant of Kounis syndrome with anaphylactic shock and myocardial ischemia, treatment with 2 L of normal saline, adrenaline, hydrocortisone, and antihistamines did not have any immediate effect, and the patient recovered in a later stage with vasopressors and myocardial infarction protocol treatment. In an atopic female nurse (10) with previous atopic eczema, asthma, and allergy to milk protein, who suffered an anaphylactic reaction, hemodynamic status was unresponsive to intravenous administration of fluids such as Ringer’s acetate and antiallergic treatment with adrenaline and corticosteroids, but the patient recovered with myocardial infarction protocol treatment. It was commented that hemodynamic disturbance was most probably due to myocardial stunning leading to reduced cardiac output rather than due to fluid extravasation. In another patient with hymenoptera sting–induced anaphylactic shock (11), urgent coronary angiography revealed acute coronary thrombosis, and the patient recovered with intra-aortic balloon pump assistance and myocardial infarction treatment. Differentiating global hypoperfusion from primary tissue suppression due to mast cell mediator action on systemic arterial vasculature seems to be challenging. Combined tissue suppression from arterial involvement and peripheral vasodilatation, perhaps, occur simultaneously. Although the mechanisms of anaphylactic shock still remain to be elucidated, the above effects resemble those during endotoxin administration and postischemic hypoperfusion (3). In this aspect, the experiments of Davidson et al (1) help to understand the pathophysiology of anaphylactic shock, but further studies are needed to determine the importance of mediators of anaphylaxis in cerebral and myocardial pathobiology. Nicholas Kounis George N. Kounis George D. Soufras Andreas Mazarakis Department of Medical Sciences Patras Highest Institute of Education and Technology Patras, Grecce

Diagnosis and management of food-induced anaphylaxis

Anaphylaxis is an acute, life-threatening, systemic reaction with varied clinical presentations and severity that results from the systemic release of mediators from mast cells and basophils. The diagnosis of food-induced anaphylaxis is based on a combination of medical history and presence of specific IgE to the responsible food. In general, the more rapid the onset of symptoms following exposure to the allergen, the more likely the reaction will be severe and life threatening. However when ingested food is the allergen, it may take up to 25 minutes from onset of anaphylaxis to cardiopulmonary arrest, making the diagnosis even more challenging. In food-induced, fatal anaphylaxis episodes up to 80% are not associated with cutaneous signs or symptoms, the signal that most patients will recognize first. Furthermore, it is well established that patients with food-induced anaphylaxis under utilize epinephrine. Thus, ongoing education for the patient who is at risk for anaphylaxis becomes essential. While occurrences of food allergy are believed to be increasing, the true prevalence is unknown. Food allergies are highest in children and adolescents and are thought to be the most common cause of anaphylaxis in the outpatient setting, accounting for approximately 30% of fatal reactions. Fatalities from food-induced anaphylaxis are highest in teenagers and young adults, among those with asthma, and in cases when there has been a delay in the administration of epinephrine. Biphasic reactions occur in approximately 25% of fatal and near-fatal, food-induced anaphylaxis events. Special circumstances involving food allergy that will be discussed include exercise-induced anaphylaxis, unsuspecting hidden food allergy, and the significance of food allergy for vaccine administration. The treatment of anaphylaxis involves the immediately administration of epinephrine. When there is any doubt about the diagnosis, it is generally best to administer epinephrine rather than waiting for more severe symptoms. In the treatment of food-induced anaphylaxis, more than a single dose of epinephrine may be required; these doses can be given every 5-10 minutes, and a longer period of observation is recommended. While IM administration is preferred by many national and international guidelines, the controversy over IM vs. subcutaneous epinephrine use will be discussed. Following the administration of epinephrine, other treatment modalities include 1) placing the patient in a supine position, 2) oxygen, and 3) fluid replacement. The role of the second line, supportive medications including H1 and H2 antihistamines and corticosteroids has not been established for the treatment of acute, biphasic, or prolonged anaphylaxis. Glucagon may be considered in patients taking a beta-blocker who are not responding to epinephrine. Physicians and office staff need to maintain clinical proficiency in anaphylaxis management, which should include an established written plan to deal with anaphylaxis and regular practice sessions. An action plan for the diagnosis and management of food-induced anaphylaxis should be provided to every patient with food allergies. A review of the action plan and technique for auto-injection of epinephrine should occur at regularly scheduled office visits. Recognizing that at the present time, there is no way to prevent food-induced anaphylaxis other than by avoiding the food. the patient requires frequent reinforcement that epinephrine, NOT antihistamines, is the only effective medication for the treatment of anaphylaxis and that a delay in administration is associated with more severe symptoms and a higher rate of fatality. Every patient with food-induced anaphylaxis must always have at least two doses of auto-injectable epinephrine immediately available.

Quantification of Volume Loss and Haemodynamic Changes of Gelofusine®-induced Anaphylaxis during Cardiopulmonary Bypass

A patient undergoing anaesthesia for coronary artery bypass surgery developed what was subsequently confirmed to be an anaphylactic reaction to succinylated gelatin (Gelofusine). By virtue of being on cardiopulmonary bypass, rapid detection, quantification and treatment of volume loss (by vasodilatation and extravasation) was possible. The patient required 51 ml/kg of resuscitative fluids in the 15 minutes after onset of anaphylaxis, or 73% of her calculated preoperative blood volume. Alpha-adrenoceptor agonists and vasopressin were required to manage ongoing vasoplegia. This case emphasises the importance of volume resuscitation and vasopressors in the treatment of anaphylaxis.

운동 유발성 알레르기 질환(FDEIA)에 미치는 영향과 기전분석

Food-dependent exercise-induced anaphylaxis (FDEIA) is a distinct form of food allergy induced by physical exercise. It is typified by the onset of anaphylaxis during exercise, which is preceded by the ingestion of causal food allergens. Diagnosis of FDEIA is heavily dependent on clinical history. To describe the physiopathological mechanism, etiologic factors, and clinical manifestations, we evaluated the spleen index, proliferation assay of lymphocyte, ROS, ASAS, and cytokines levels in sensitized and exercise-trained mice. One-hundred mice were bred in the animal lab at D and P university under controlled conditions [22±2℃, RH 45-55%, and a 12-hour photoperiod]. Animals are 7-weeks-old at the time of study and were fed a standard commercial chow diet from 09:00 to 15:00 over the 8-week study period. The mice were allowed access to distilled deionized water ad libitum. Daily food intake and weekly body gains were routinely recorded throughout the experimental period using computing scale (CAS). Mice were divided into the control group (S; control sensitized, n=25), 30 min swim training group (S30, N=25), 50 min swim training group (S50, N=25), and 80 min swim training group (S80, N=25). The results were as follows: Spleen index showed the highest level in the S80 group compared to other groups; this level was exercise-dependent. In proliferation assay of Med and OVA, the S80 group showed the highest level compared to the other groups; this level also was exercise intensity-dependent. Peritoneal ROS and IL-4 showed a statistically significant difference compared to S; however, there was no significant differences in ROS among S30, 50, and 80. From the results, we concluded that FDEIA is correlated with exercise intensity based on the levels of peritoneal ROS and cytokine profiles.

PRE-EXPOSURE TO VASOPRESSIN POTENTIATES THE VASOCONSTRICTIVE EFFECT OF EPINEPHRINE IN RAT AORTA ISOLATED DURING LATE ANAPHYLAXIS

Clinical guidelines for anaphylaxis recommend epinephrine as first-line therapy but do not distinguish between early and late stages of anaphylaxis. The delay between the onset of anaphylaxis and initiation of treatment may influence the choice of the optimal vasoconstrictor (epinephrine versus arginine vasopressin [AVP]). Anesthetized rats were allocated into control and three anaphylaxis groups (n = 6 per group). The aortas were removed at 5 min (control) and at 5, 15, or 30 min during anaphylaxis and were contracted in organ baths by increasing concentrations of epinephrine or AVP. After washout of the initial agonist, each ring was contracted with the alternative drug. Separately, aortic rings removed during early versus late anaphylaxis were contracted by AVP +/- pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME) (10 M), a NOS inhibitor. Aortic rings removed during late versus early anaphylaxis were less responsive to epinephrine (EC50 at 5 min, 8.4 nM [4.9 - 11.8]; EC50 at 30 min, 18.2 nM [11.9 - 24.4]; P = 0.04) and AVP (EC50 at 5 min, 8.1 nM [4.9 - 11.3]; EC50 at 30 min, 19.7 nM [10.9 - 28.6]; P = 0.02). Pre-exposure to AVP enhanced the subsequent contractile effect of epinephrine in aortic rings removed during late anaphylaxis (maximal contractile effect, 1.02 g [0.76 - 1.28]) versus early anaphylaxis (maximal contractile effect, 0.44 g [0.28 - 0.59]; P = 0.005). In contrast to early anaphylaxis, pretreatment with L-NAME decreased responsiveness to AVP during late anaphylaxis (EC50, 2.47 nM [1.79 - 3.16], 1.55 nM [1.11 - 1.98] for +/- L-NAME, respectively; P = 0.03). During anaphylaxis, the vasoconstrictive effects of AVP or epinephrine were time dependent. Arginine vasopressin might have beneficial effects during late anaphylaxis via mechanisms involving NO.

Test Use Evaluation of Serum Tryptase Levels

RATIONALE: Guidelines for the blood tryptase test recommend specimen collection 1/4 to 3 hours after onset of anaphylaxis (A) or severe allergy (SA) and follow-up basal level. For mast cell disease (MCD) repeat testing is advised. This study evaluated the frequency of guideline compliance.

환경, 음식 및 운동 알레르기 반응에 대한 고찰

규칙적인 운동이 면역력 증가에 도움을 주는 것이 일반적인 사실이지만 차고 건조한 환경에서의 격렬한 운동은 호흡기 질환의 일종인 운동 유발성 천식과 운동 유발성 알레르기 질환을 야기하고, 상기도 감염 등을 유발하기도 한다. 이는 수행되는 운동의 종류나 방법 등에 따라서 다르게 나타나며 운동 수행의 경험과 운동 환경 등에 따라서 상이하게 나타난다. 따라서 운동하는 환경이 야외에서 이루어지며 오존이나 먼지 등을 많이 접하면서 수행되는 운동과 동계 스포츠인 스키, 스노우보드, 스케이트 및 아이스하키와 같은 운동 수행으로 운동 시 폐가 차갑고 건조한 공기에 장시간 노출됨에 따라 운동 유발성 천식과 운동유발성 알레르기 반응이 초래된다. 이러한 반응은 음식 알레르기와도 함께 나타나는데, 음식 알레르기가 있는 사람은 운동 시 더욱 알레르기 반응이 증가하게 되고, 음식 알레르기가 나타나지 않은 사람도 특정 음식 섭취 후 격렬한 운동 시 운동 유발성 알레르기가 나타나기도 한다. 이는 일반적으로 소화된 음식물이 장으로 지나갈 때, 혈액의 IgA가 덜 소화된 단백질을 혈액으로 들어오는 것을 방어해 주지만, 결렬한 운동이나 스트레스 상황에서는 IgA가 감소하게 되고, 이러한 상황에서 음식 유발성 알레르기 질환이 나타나게 되는데, 운동 시 이러한 반응이 더욱 심화되며 운동 유발성 알레르기 아나플락시스로 나타나기도 한다. 운동 유발성 알레르기 질환은 운동의 방법, 종류 및 수행되는 운동시간 등에 따라 깊은 관련이 있으며, 임상적인 징후로는 심한 기침, 가슴의 답답함, 호흡 곤란, 쌕쌕거림의 현상, 피부두드러기 및 혈관부종, 심할 경우 혈관파괴 등의 현상이 나타나고, 돌연사의 원인이 되기도 한다. 격렬한 운동은 과 호흡을 유발시키고, 이로 인해 폐의 비만세포가 증가하게 되며, 증가된 비만세포에서 나오는 히스타민이 알레르기 반응을 유발한다. 운동 유발성 두드러기나 아나필락시스 진단에 있어 가장 중요한 사항은 가족력과 병력에 대한 사항이며, 이외에도 메타콜린 피부 반응검사 등이 있다. 치료는 일상생활에서 활동의 수준과 범위를 수정하는 하는 것이 핵심이며, 이를 위해서는 전문가를 통한 환자 교육이 매우 중요하며, 식후에는 시간을 두고 운동해야 한다. 그리고 운동전 알레르기를 유발하는 음식물의 섭취를 제한해야 한다. 본 연구자는 운동 알레르기와 관련된 인자를 크게 운동 시의 환경과 음식물로 구분하고, 여러 문헌을 고찰하여, 운동 시 일어날 수 있는 알레르기 반응을 미연에 방지하고, 운동을 수행하는 엘리트 운동선수 및 동호인, 운동을 지도하는 지도자, 스포츠 산업에 종사하는 사람들에게 기초자료를 제공하고자 한다. Exercise-induced anaphylaxis (EIA) is a physical allergy, sometimes severe, triggered by exertion following specific food intake. It was defined for the first time in 1980. EIA is associated with different kinds of exercise. The clinical manifestations progress from itching, erythema and urticaria to some combination of cutaneous angioedema and vascular collapse. Mast cell participation in the pathogenesis of this syndrome has been proved by the findings of an elevated serum histamine level during exhaustive exercise. As predisposing factors of EIA, a specific or even nonspecific sensitivity to food has been reported. Food-dependent exercise-induced anaphylaxis (FDEIA) is a distinct form of food allergy induced by physical exercise. It is typified by the onset of anaphylaxis during exercise which was preceded by the ingestion of the causal food allergens. The diagnosis of FDEIA is heavily dependent on clinical history. Allergy tests may need to be performed using a broad panel of food and food additives. As with food allergies, FDEIA diagnosis is based on interview, biological test and skin test. Prophylaxis aims to prevent a recurrence; the patient should be given an emergency kit to deal with any recurrent episodes. After the food allergen has been identified, it should be avoided for at least 4 to 5 hours before any exercise. Two cases of EIA are presented (EIA to circumstances; FDEIA) in this paper, The diagnosis, pathophysiology and therapy of FDEIA are also reviewed.

Postmortem Findings After Anaphylactic Reactions to Drugs in Turkey

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. 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. 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. 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.

Increased production of cysteinyl leukotrienes and prostaglandin D2 during human anaphylaxis

Anaphylaxis is a life-threatening syndrome resulting from the sudden release of mast cell- and basophil-derived mediators into the circulation. However, pathological evidence of the association between inflammatory mediators and human anaphylaxis is insufficient. The aim of this study was to better understand the relationship between in vivo production of inflammatory mediators and the pathogenesis of anaphylaxis. We also sought to evaluate mast cell activation in anaphylaxis. We measured the concentrations of various inflammatory mediators in urine samples, which were collected from 32 anaphylactic patients during the onset of anaphylaxis and during clinical remission, 21 patients with asthma on acute exacerbation and 15 healthy control subjects. Blood and urine specimens were collected from the patients after provocation test. Urinary leukotriene E4 (LTE4), 9alpha, 11beta-prostaglandin F2 (9alpha, 11beta-PGF2), eosinophil-derived neurotoxin (EDN) and leukotriene B4 glucuronide (LTBG) concentrations were determined by enzyme immunoassay, and the activity of plasma platelet-activating factor acetylhydrolase and serum tryptase concentration were measured using commercially available kits. Significantly higher concentrations of urinary LTE4 and 9alpha, 11beta-PGF2, which immediately decreased during clinical remission, were observed in the anaphylactic patients than in asthmatic patients on acute exacerbation and healthy control subjects. Concentrations of EDN and LTBG were not significantly different among the anaphylactic patients, asthmatic patients on acute exacerbation and healthy subjects. There was a significant correlation between urinary LTE4 and 9alpha, 11beta-PGF2 concentrations in the anaphylactic patients (r=0.672, P=0.005, n=32). In addition, LTE4 concentration in patients with anaphylactic shock is significantly elevated compared with that in patients without anaphylactic shock. This is a report on the significant increase in urinary LTE4 and 9alpha, 11beta-PGF2 concentrations during anaphylaxis. Urinary LTE4 and 9alpha, 11beta-PGF2 concentrations may be a reliable marker of endogenous production of inflammatory mediators associated with anaphylaxis.

Food‐dependent exercise‐induced anaphylaxis in childhood

The clinical syndrome of food-dependent exercise-induced anaphylaxis (FDEIA) is typified by the onset of anaphylaxis during (or soon after) exercise which was preceded by the ingestion of the causal food allergen/s. In FDEIA, both the food allergen/s and exercise are independently tolerated. FDEIA is an uncommon allergic condition in childhood, but nonetheless is an important differential diagnosis to be considered when faced by a child who has experienced exercise-associated anaphylaxis. The diagnosis of FDEIA is heavily dependent on the clinical history. Allergy tests may need to be performed to a broad panel of food and food additives. Modified exercise challenges (performed with and without prior ingestion of food) are frequently required as allergy test results frequently return low-positive results. A diagnosis of FDEIA facilitates the safe independent return to exercise and reintroduction of foods for patients who otherwise may unnecessarily avoid exercise and/or restrict their diet. The natural history of FDEIA is unknown; however, a safe return is usually achieved when the ingestion of the causal food allergen/s and exercise are separated.

Gastrointestinal Disorders in Anaphylaxis

We report two rare cases complicated by gastrointestinal mucosal disorders, including peptic ulcer and ischemic colitis. Anaphylaxis was induced by cefaclor in case 1 and by pranoprofen in case 2. These two patients developed epigastric or lower abdominal pain about 10 hours after the onset of anaphylaxis. Gastroduodenoscopy revealed severe ulcers in the stomach or duodenum, while colonoscopy detected mucosal edema, erythema, and erosions, leading to the diagnosis of ischemic colitis. It is important to keep in mind that gastrointestinal mucosal lesions can occur, albeit on rare occasions, in patients with anaphylaxis.

Delayed food-dependent, exercise-induced anaphylaxis

Food-dependent, exercise-induced anaphylaxis (FDEIA) is a clinically distinct form of anaphylaxis in which symptoms occur only when the patient exercises within a few hours of eating the food. Its precise mechanism remains unclear and has been reported to have a wide spectrum of presentations. The objective of this report is to show that the onset of FDEIA can be delayed for several hours and to emphasize the critical need for having self-injectable epinephrine available at all times. Our patient had several episodes of FDEIA to wheat shortly after exercise since the age of 11 years. At 16 years of age, 5 hours after exercise that followed eating a wheat-containing meal, the patient developed severe anaphylaxis with loss of consciousness. Skin-prick test was positive (4+) to wheat but negative to 41 other foods. Serum tryptase level 2 hours after onset of anaphylaxis was elevated. Other laboratory findings were within normal ranges. This case indicates that FDEIA can have a delayed onset for several hours. Because such delayed onset is unpredictable and can be life-threatening, it might be prudent for such patients to avoid the offending food totally or to avoid exercising for at least 6 hours after eating the food and to keep self-injectable epinephrine easily available at all times.

Anaphylactic deaths in Auckland, New Zealand: a review of coronial autopsies from 1985 to 2005

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. 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. 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. 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.

Un dosage de tryptase sérique dans des situations d’urgence est-il utile ?

Serum tryptase is a specific indicator of systemic allergic reactions. The aim of the present study was to evaluate the value of serum tryptase determinations in diagnosing anaphylactoid reactions and sudden deaths in an emergency room. Tryptase concentrations were determined using the Pharmacia UniCap-Tryptase fluoro-immuno-assay in 21 patients referred to the emergency room of our hospital. A diagnosis of anaphylaxis was established by an allergologist based on clinical criteria. The tryptase level was increased in 5 out of 8 patients in anaphylactic shock. In the 3 other patients, the level was within normal limits (false negative), probably because of the delay in obtaining the blood sample from them. In 5 cases of non-anaphylactic sudden death, the tryptase level was within normal limits; in 1 other case, a false positive result was due to attempted cardiac resuscitation. This study confirms previous observations that serum tryptase is not increased in cases of non-anaphylactic sudden cardiac or respiratory arrest, except in those cases where thoracic compression precedes the venipuncture. Thus, determination of the serum tryptase level should be useful in cases of unexplained sudden death. Nevertheless, a normal serum tryptase level does not exclude a diagnosis of anaphylaxis, given the possibility of false negative results. To avoid this, it is essential that the blood sample for this assay should be obtained within 2 h of the onset of anaphylaxis.

Commentary on the Revised Vaccine Injury Table

New guidelines for the national Vaccine Injury Compensation Program (VICP) have been announced. Several important changes are included in the revised Vaccine Injury Table. First, a new condition of chronic arthritis was added to the Table for vaccines containing the attenuated rubella virus. Second, the time of onset for certain conditions in relation to the time of vaccine administration was altered. For instance, the interval for onset of anaphylaxis after vaccination was shortened from 24 hours to 4 hours. Clarification of definitions of conditions such as encephalopathy were made in the Qualifications and Aids to Interpretation that accompany the Table. Finally, some conditions, such as residual seizure disorder and hypotonic-hyporesponsive episode after diphtheria-tetanus-pertussis (DTP) immunization, were removed from the Table.