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Anaphylaxis is a potentially life-threatening, multisystem allergic reaction that can cause airway, breathing, or circulatory compromise. Intramuscular epinephrine is the immediate treatment of all patients. Intravenous epinephrine should be used in patients in shock, either as a bolus or infusion, along with fluid resuscitation. Airway obstruction must be recognized, and early intubation may be necessary. For shock that is refractory to epinephrine, additional vasopressors may be needed. Disposition depends on patient presentation and response to treatment. Mandatory observation periods are not necessary, because biphasic reactions are difficult to predict and may occur outside of typical observation periods., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The use of inconsistent definitions for anaphylaxis outcomes limits our understanding of the natural history and epidemiology of anaphylaxis, hindering clinical practice and research efforts., Objective: Our aim was to develop consensus definitions for clinically relevant anaphylaxis outcomes by utilizing a multidisciplinary group of clinical and research experts in anaphylaxis., Methods: Using Delphi methodology, we developed agenda topics and drafted questions to review during monthly conference calls. Through online surveys, a 19-member panel consisting of experts in allergy and/or immunology and emergency medicine rated their level of agreement with the appropriateness of statements on a scale of 1 to 9. A median value of 1.0 to 3.4 was considered inappropriate, a median value of 3.5 to 6.9 was considered uncertain, and a median value of 7.0 to 9.0 was considered appropriate. A disagreement index was then calculated, with values less than 1.0 categorized as "consensus reached." If consensus was not reached after the initial survey, subsequent surveys incorporating the aggregate de-identified responses from prior surveys were sent to panel members. This process was repeated until consensus was reached or 4 survey rounds had been completed, after which the question was categorized as "no consensus reached.", Results: The panel developed outcome definitions for persistent, refractory, and biphasic anaphylaxis, as well as for persistent and biphasic nonanaphylactic reactions. There was also consensus among panel members regarding the need to develop an anaphylaxis severity grading system., Conclusion: Dissemination and application of these definitions in clinical care and research will help standardize the terminology used to describe anaphylaxis outcomes and serve as the foundation for future research, including research aimed at development of an anaphylaxis severity grading system., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Food allergies are defined as adverse immune responses to food proteins that result in typical clinical symptoms involving the dermatologic, respiratory, gastrointestinal, cardiovascular, and/or neurologic systems. IgE-mediated food-allergic disease differs from non-IgE-mediated disease because the pathophysiology results from activation of the immune system, causing a T helper 2 response which results in IgE binding to F c ε receptors on effector cells like mast cells and basophils. The activation of these cells causes release of histamine and other preformed mediators, and rapid symptom onset, in contrast with non-IgE-mediated food allergy which is more delayed in onset. The diagnosis of IgE-mediated food allergy requires a history of classic clinical symptoms and evidence of food-specific IgE by either skin-prick or serum-specific IgE testing. Symptoms of IgE-mediated food allergies range from mild to severe. The severity of symptoms is not predicted by the level of specific IgE or skin test wheal size, but the likelihood of symptom onset is directly related. Diagnosis is excluded when a patient can ingest the suspected food without clinical symptoms and may require an in-office oral food challenge if testing for food-specific IgE by serum or skin testing is negative or low. Anaphylaxis is the most severe form of the clinical manifestation of IgE-mediated food allergy, and injectable epinephrine is the first-line treatment. Management of food allergies requires strict avoidance measures, counseling of the family about constant vigilance, and prompt treatment of allergic reactions with emergency medications. Guidelines have changed recently to include early introduction of peanuts at 4-6 months of life. Early introduction is recommended to prevent the development of peanut allergy. Future treatments for IgE-mediated food allergy evaluated in clinical trials include epicutaneous, sublingual, and oral immunotherapy.

We review the history of the classification and coding changes for anaphylaxis and provide current and perspective information in the field. In 2012, an analysis of Brazilian data demonstrated undernotification of anaphylaxis-related deaths because of the difficulties of coding using the International Classification of Diseases, 10th Revision. This work triggered strategic international actions supported by the Joint Allergy Academies and the International Classification of Diseases World Health Organization (WHO) leadership to update the classification of allergic disorders for the International Classification of Diseases, 11th Revision (ICD-11), which resulted in construction of the pioneer "Allergic and hypersensitivity conditions" chapter. The usability of the new framework has been tested by evaluating the same data published in 2012 from the ICD-11 perspective. Coding accuracy was much improved, reaching 95% for definite anaphylaxis. As the results were provided to the WHO Mortality Reference Group, coding rules have been changed, allowing anaphylaxis to be recorded as an underlying cause of death in official mortality statistics. The mandatory use of ICD-11 from January 2022 for documenting cause of death could have 2 immediate consequences: (1) the reported number of anaphylaxis-related deaths might increase because of more appropriate coding and (2) the cross-sectional and longitudinal mortality data generated might ultimately lead to a better understanding of anaphylaxis epidemiology and improved health policies directed at reducing anaphylaxis-related mortality., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The study of allergic drug reactions has been limited because of challenges in identifying and confirming cases., Objective: To determine the utility of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for identifying inpatient allergic drug reactions and to compare findings with previous data in the emergency department., Methods: By reviewing medical records of inpatients with ICD-9-CM codes and E codes suggestive of allergic drug reactions at a large urban academic medical center, we determined codes that yielded the most drug allergy cases and identified culprit drugs., Results: In 2005 and 2010, 3337 and 5282 possible allergic drug reactions during hospitalization were identified and 1367 were reviewed. Allergic drug reactions were found in 409 (30.1%) of the reviewed charts, with 172 (29.7%) in 2005 and 237 (30.5%) in 2010. The codes that identified the highest percentage of true allergic drug reactions were dermatitis due to drug (693.0), allergic urticaria (708), angioneurotic edema (995.1), and anaphylaxis (995.0). Antibiotics were the most common cause (44.4%); however, multiple drug classes were often identified as likely culprit drugs., Conclusion: Specific ICD-9-CM codes can identify patients with allergic drug reactions, with antibiotics accounting for almost half of true reactions. Most patients with codes 693.0, 995.1, 708, and 995.0 had allergic drug reactions, with 693.0 as the highest yield code. An aggregate of multiple specific codes consistently identifies a cohort of patients with confirmed allergic drug reactions., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Introduction: In May 2008, the Food and Drug Administration launched the Sentinel Initiative, a multi-year program for the establishment of a national electronic monitoring system for medical product safety that led, in 2016, to the launch of the full Sentinel System. Under the Mini-Sentinel pilot, several algorithms for identifying health outcomes of interest, including one for anaphylaxis, were developed and evaluated using data available from the Sentinel common data model., Purpose: To evaluate whether features extracted from unstructured narrative data using natural language processing (NLP) could be used to classify anaphylaxis cases., Methods: Using previously developed methods, we extracted features from unstructured narrative data using NLP and applied rule-based and similarity-based algorithms to identify anaphylaxis among 62 potential cases previously classified by human experts as anaphylaxis (N = 33), not anaphylaxis (N = 27), and unknown (N = 2)., Results: The rule-based and similarity-based approaches demonstrated almost equal performance (recall 100% vs 100%, precision 60.3% vs 57.4%, F-measure: 0.753 vs 0.729). Reasons for misclassification included the inability of the algorithms to make the same clinical judgments as human experts about the timing, severity, or presence of alternative explanations; and the identification of terms consistent with anaphylaxis but present in conditions other than anaphylaxis., Conclusions: Although precision needs to be improved before these algorithms could be used without human review, we demonstrated that applying rule-based and similarity-based algorithms to unstructured narrative information from clinical records can be used for classification of anaphylaxis in the Sentinel System. Further development and assessment of these methods in the Sentinel System are warranted., (© 2018. This article is a U.S. Government work and is in the public domain in the USA.)

Background Pharmacovigilance databases are utilized to identify serious adverse drug events (ADEs). In China, very few studies have evaluated the validity of using pharmacovigilance databases to identify drug-induced anaphylaxis (DIA). Objective We aimed to develop and validate an algorithm to identify DIA using the Beijing Pharmacovigilance Database (BPD). Setting ADEs from the BPD mainly spontaneously reported from 94 hospitals in Beijing, China. Method Using the diagnoses, we developed an algorithm to identify potential DIAs from the BPD between January 2004 and December 2014. A sample of 500 patients was randomly selected for chart abstraction. Two physician adjudicators assessed whether DIA occurred using the published clinical criteria as the gold standard. Main outcome measure Positive predictive values (PPVs) and 95% confidence intervals of the algorithm and algorithm criteria components were calculated. Results 500 patients (53.2% female; the mean age 48.2 years) with potential DIA were selected using the algorithm. 444 were adjudicated as having anaphylaxis by physicians. The PPV of the overall algorithm was 88.8% (95% CI 86.0-91.6%). PPV for the algorithm only using specific diagnoses of "anaphylactic shock", "anaphylactic reaction", and "anaphylactoid reaction [severe]" was 89.6% (95% CI 86.6-92.4%); this partial algorithm identified 387 (87.2%) DIAs. The diagnosis that identified the most DIAs (83.8%) was "anaphylactic shock", with a PPV of 91.6% (95% CI 88.9-94.3%). Conclusion The overall algorithm identified a greater number of DIAs than the algorithm that only used specific diagnoses; however, its PPV was slightly lower. We were able to identify DIAs with the algorithm we developed.

Vasoplegia is the syndrome of pathological low systemic vascular resistance, the dominant clinical feature of which is reduced blood pressure in the presence of a normal or raised cardiac output. The vasoplegic syndrome is encountered in many clinical scenarios, including septic shock, post-cardiac bypass and after surgery, burns and trauma, but despite this, uniform clinical definitions are lacking, which renders translational research in this area challenging. We discuss the role of vasoplegia in these contexts and the criteria that are used to describe it are discussed. Intrinsic processes which may drive vasoplegia, such as nitric oxide, prostanoids, endothelin-1, hydrogen sulphide and reactive oxygen species production, are reviewed and potential for therapeutic intervention explored. Extrinsic drivers, including those mediated by glucocorticoid, catecholamine and vasopressin responsiveness of the blood vessels, are also discussed. The optimum balance between maintaining adequate systemic vascular resistance against the potentially deleterious effects of treatment with catecholamines is as yet unclear, but development of novel vasoactive agents may facilitate greater understanding of the role of the differing pathways in the development of vasoplegia. In turn, this may provide insights into the best way to care for patients with this common, multifactorial condition.

Background: Although currently misclassified in the International Classification of Diseases (ICD) and still not officially listed as a rare disease, anaphylaxis is a well-known clinical emergency. Anaphylaxis is now one of the principal headings in the "Allergic and hypersensitivity conditions" section recently compiled for the forthcoming 11 th Revision of ICD (ICD-11). We here report the building process used for the pioneering "Anaphylaxis" subsection of ICD-11 in which we aimed for transparency as recommended in the ICD-11 revision guidelines., Results: During an online intensive scientific and technical discussions with ICD-11 Topic Advisory Groups and Expert Working Groups, we drafted a total of 35 proposals for the classification of anaphylaxis. From all the 35 proposals, 77% were implemented, 20% remain to be implemented, and the others being partially implemented (1.5%) or rejected (1.5%)., Conclusion: For the first time, anaphylaxis is now properly classified and has attained greater visibility within ICD. In addition to all the benefits expected from the actions we have undertaken in updating the terminology, definitions and classification of allergic and hypersensitivity conditions for ICD-11, we strongly believe that anaphylaxis should be a public health priority and that it should therefore be formally added into the list of rare diseases in order to support awareness and quality clinical management of patients.

Anaphylaxis is defined as a serious allergic or hypersensitivity reaction in the most cases as a result of an IgE-mediated allergic reaction that is rapid in onset and may cause death. Common triggers are foods, insect stings, and medications. The medical treatment includes, epinephrine, glucocorticoids, antihistamines and inhaled bronchodilators, with the aim to prevent progression to life-threatening respiratory and/or cardiovascular symptoms.

Bee and wasp stings can cause allergic reactions. Although the local reactions are more frequent, anaphylaxis due to insect stings can be potentially fatal. Rapid recognition of anaphylaxis is therefore critical and reactions should immediately be treated with i.m. adrenaline. Patients having experienced anaphylaxis should be referred to an allergist for diagnostic evaluation and possible venom-immunotherapy (VIT). The clinical history is essential in diagnosis of venom allergy as the test results are not always reliable. Diagnostic testing with venom components might be beneficial in appropriate patients. The analysis of serum tryptase from the acute episode can be crucial. Mastocytosis is associated in about 8 percent of patients with severe anaphylaxis from insect stings and should be considered in the differential diagnosis. VIT is indicated for patients with a history of anaphylaxis and is effective in preventing future anaphylaxis from Hymenoptera stings.

Anaphylaxis is an acute, severe, systemic hypersensitivity reaction and is potentially fatal. It is sudden and almost always unanticipated, and it involves more than one organ system. Symptom onset varies widely from within seconds to a few hours, but usually occurs within 30 minutes of exposure to the trigger. Early diagnosis and prompt initiation of treatment is important and the diagnosis should be established only when the diagnostic criteria are met. Any delay in the recognition of the initial signs and symptoms can result in a fatal outcome, either because of airway obstruction or circulatory collapse. Adrenaline is the drug of choice and should be immediately administered intramuscularly with suspected reaction.

Purpose: Radiology residencies are increasingly using clinical simulation to teach contrast reaction management. The aim of this study was to evaluate resident documentation of management and transfer of care in severe contrast reactions after a clinical simulation., Methods: After a high-fidelity mannequin simulation of contrast-induced anaphylactic shock, residents (n = 18) were asked to document the event in a progress note and transfer care to a receiving medical team. A total of 22 prospectively determined criteria were selected, and notes were analyzed by a blinded reviewer., Results: Notes contained between 12 and 21 of the prospectively determined 22 criteria (54%-95%). The median number of criteria contained in a note was 16. None of the notes fulfilled all 22 criteria. However, consistent deficiencies were found in documenting prior reaction to contrast (28%) and transfer-of-care criteria (22%-44%)., Conclusions: Although standards for the documentation of advanced cardiovascular life support codes and other emergencies have been devised, no such standards exist for documentation in the management of contrast reactions. The results of this study suggest the need to develop a standardized documentation system for severe contrast-induced reactions. Education regarding transfer of care and documentation should be emphasized during clinical simulation., (Copyright © 2015 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Aim: Emergency department (ED) visits for food-related acute allergic reactions enable estimation of temporal trends in food allergy prevalence. To use this approach in New Zealand requires an understanding of the proportion of ED visits coded as 'anaphylaxis, unspecified' or 'allergy, unspecified' that are food-related allergic reactions., Method: We reviewed all ED presentations of children, coded as 'anaphylaxis, unspecified' or 'allergy, unspecified', from 1988-2011 to the Auckland City Hospital ED. Charts were reviewed independently by two investigators to determine agreement on categorisation of presentations as being food-related acute allergic reactions. We compared ED presentation rates in different time intervals using rate ratios (RR) and 95% confidence intervals (CI)., Results: Sixty-five (29%) of the 221 ED presentations given a discharge code of 'anaphylaxis, unspecified' or 'allergy, unspecified', were a food-related allergic reaction. Inter-observer agreement was very good (kappa >0.80). The ED presentation rate with food-related allergic reactions in 2004-2011 was 98% higher than in 1988-1995 (RR=1.98, 95%CI 1.10-3.72). By contrast, ED presentation rates for non-food-related allergic reactions did not change over these years., Conclusion: ED presentations for food-related allergic reactions are identifiable from within ED presentations coded as 'anaphylaxis, unspecified' or 'allergy, unspecified'. ED presentations for food-related allergic reactions have increased over time in Auckland.

Anaphylaxis is a potentially life-threatening systemic allergic reaction involving several organ systems. Recognition of the reaction leading to prompt treatment is essential for a good outcome. The lifesaving treatment is intramuscular injection of adrenaline (0.3-0.5 mg for adults and children > 40 kg, 0.3 mg for children 20-40 kg and 0.15 mg for infants < 20 kg). The patient must be placed on the back with elevated lower extremities to improve cerebral and cardiac circulation. High dose oxygen and crystalloid fluid load are needed to improve oxygenation and cardiac output.

Anaphylaxis is a potentially life-threatening systemic allergic reaction involving several organ systems. Recognition of the reaction leading to prompt treatment is essential for a good outcome. The lifesaving treatment is intramuscular injection of adrenaline (0.3-0.5 mg for adults and children > 40 kg, 0.3 mg for children 20-40 kg and 0.15 mg for infants < 20 kg). The patient must be placed on the back with elevated lower extremities to improve cerebral and cardiac circulation. High dose oxygen and crystalloid fluid load are needed to improve oxygenation and cardiac output.

In forensic pathology routine, fatal cases of contrast agent exposure can be occasionally encountered. In such situations, beyond the difficulties inherent in establishing the cause of death due to nonspecific or absent autopsy and histology findings as well as limited laboratory investigations, pathologists may face other problems in formulating exhaustive, complete reports, and conclusions that are scientifically accurate. Indeed, terminology concerning adverse drug reactions and allergy nomenclature is confusing. Some terms, still utilized in forensic and radiological reports, are outdated and should be avoided. Additionally, not all forensic pathologists master contrast material classification and pathogenesis of contrast agent reactions. We present a review of the literature covering allergic reactions to contrast material exposure in order to update used terminology, explain the pathophysiology, and list currently available laboratory investigations for diagnosis in the forensic setting.

Minor and major allergic reactions occur during oral and maxillofacial treatment. Immediate diagnosis and pharmacologic intervention are imperative. Signs and symptoms may be variable. The early administration of epinephrine is critical., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Undernotification is well recognized as a key challenge to the study of anaphylaxis mortality, but it is seldom mentioned that one of its reasons is the difficult coding of the condition under the tenth revision of the international classification of diseases (ICD-10), given that there are no anaphylaxis-specific ICD-10, which are considered valid for coding underlying causes-of-death, and that official mortality statistics consider exclusively the underlying and disregard the contributing causes-of-death data recorded on death certificates. Brazilian mortality data were used as a case study to call attention to the inadequacy of the ICD-10 for the measurement of anaphylaxis deaths., Methods: Underlying and contributing causes-of-death data were used to estimate the rates of anaphylaxis deaths in the country over the years 2008-2010., Results: Of 498 anaphylaxis deaths were found, of which 75% were classified as 'definite' and 25% as 'possible anaphylaxis deaths'. The average national rate for these years was 0.87 per million per year. None of these deaths would have been found had we exclusively considered information from the underlying cause-of-death field., Conclusion/recommendations: The study of anaphylaxis mortality using secondary data requires the use of information derived from the underlying as well as from the contributing causes-of-death fields. Coding definitions should be standardized with a view of enabling trend analyses and international comparisons. The ICD-11 revision is a unique opportunity to improve the coding system so as to facilitate epidemiological studies of anaphylaxis mortality. Educational interventions targeted at improving the quality of death certificate completion are urgently needed., (© 2012 John Wiley & Sons A/S.)

Background: The types of agents implicated to trigger intraoperative anaphylactic reactions vary among reports, and there are no recent series from the United States. In this retrospective study, we examined perioperative anaphylactic reactions that occurred at a major tertiary referral academic center., Methods: To characterize perioperative allergens associated with anaphylactic reactions, we reviewed the Mayo Clinic Division of Allergic Diseases skin test database between 1992 to 2010. The records of all patients who were tested for perioperative and anesthetic medications were reviewed. Charts that included a detailed history obtained by an allergist, skin test results, and tryptase measurements when available were reviewed and categorized., Results: Thirty-eight patients were found to have an anaphylactic reaction during anesthesia, of which 18 were immunoglobulin (Ig)E-mediated anaphylactic reactions (likely causative agent identified by skin test), 6 were non-IgE-mediated anaphylactic reactions (elevated tryptase levels and negative skin test), and 14 were probable non-IgE-mediated anaphylactic reactions (tryptase levels normal or not obtained and negative skin test). Of the IgE-mediated anaphylactic reactions, antibiotics were the most prevalent likely causative agent (50%) whereas neuromuscular blocking drugs were implicated as a likely causative agent in 11% of reactions., Conclusion: Antibiotics were the most common likely causative agent associated with IgE-mediated anaphylactic reactions; however, for 52.6% of reactions, a causative agent could not be determined, suggesting a non-IgE-mediated anaphylactic reaction. The undiagnosed allergic reactions place patients at risk of a subsequent reexposure to the same allergen, or lead to unnecessary avoidance of needed medications.

It introduced the case definition by the Brighton classification applied internationally and widely for the anaphylaxis following immunization.

IgG-mediated anaphylaxis occurs in mice and may contribute to human reactions to infused drugs. To distinguish IgE- from putative IgG-mediated human anaphylaxis, we developed blood markers for murine anaphylaxis and evaluated their human relevance. Both IgG- and IgE-mediated anaphylaxis were characterized by decreased basophil and monocyte percentages and an increased neutrophil percentage in mouse blood. IgE- but not IgG-mediated murine anaphylaxis was accompanied by large increases in IL-4 secretion, plasma soluble IL-4 receptor-α (IL-4Rα) concentration, and T-cell membrane IL-4Rα expression. T-cell IL-4Rα expression also increased when mice that express human Fcε receptor Iα were sensitized with IgG-depleted serum from a peanut-allergic individual and challenged with peanut extract. Increased T-cell IL-4Rα expression is likely to also be a marker for human IgE-mediated anaphylaxis, because IgE-activated human basophils secrete IL-4, and IL-4 increases human T-cell IL-4Rα expression in vitro. Murine IgG- but not IgE-mediated anaphylaxis was characterized by decreased neutrophil Fcγ receptor III (FcγRIII) expression that was observed even when the antigen dose was insufficient to induce shock. Human neutrophils cultured with IgG immune complexes also lost FcγRIII. These observations suggest that decreased blood neutrophil FcγRIII expression without increased IL-4Rα expression can be used to determine whether and when IgG-mediated anaphylaxis occurs in man.

Correct management and classification of anaphylaxis is mandatory. Records of emergency department (ED) visits to any of the three pediatric hospitals in Stockholm, because of reactions to foods during 2007, were identified. A retrospective analysis of clinical ED records of 371 children with 381 unique occasions of reactions to foods was performed. Symptoms/signs of reactions to foods recorded for classification of anaphylaxis were related to those presented in the EAACI Taskforce position paper on Anaphylaxis in Children (Allergy 2007; 62: 857). Forty-six different symptoms/signs of reactions to foods were retrieved. Several severe signs or symptoms from the respiratory tract and signs indicating reduced brain perfusion were not described in detail in the EAACI paper, hampering correct classification of anaphylaxis including grading of severity in our material. After modification of the EAACI classification including such signs and symptoms, we were able to classify 128 (35%) children with anaphylaxis. Seventy children (19%) did not fulfill our modified EAACI's criteria for anaphylaxis. They had been given adrenaline before or at arrival to hospital, possibly preventing anaphylaxis. Another 173 (47%) children/adolescents had neither been given adrenalin, nor fulfilled the criteria for anaphylaxis. Classification of food-induced anaphylaxis and severity grading should be built on signs and symptoms to facilitate diagnosis. The existing EAACI tool is helpful, but for Swedish children it is not quite applicable, in particular because of the lack of description of some respiratory, neurological or possible cardiovascular signs and symptoms., (© 2010 John Wiley & Sons A/S.)

Anaphylactic reactions to hymenoptera venoms are common and, in our latitudes, mainly concern wasps and bees. Recently, molecular biology techniques have contributed to identifying and to sequencing the major allergens of insect venoms and led to the production of recombinant allergens. Assays for specific IgE directed against these recombinant allergens have recently been made available in clinical practice. They provide considerable assistance in identifying the insect responsible for an anaphylactic reaction, in particular when standard tests are positive for both wasp and bee. This article focuses on these new laboratory tests and also reviews the management of patients experiencing an anaphylactic reaction after hymenoptera sting.

Anaphylaxis as the maximal variant of an acute systemic hypersensitivity reaction can involve several organ systems, particularly the skin, respiratory tract, gastrointestinal tract and the cardiovascular system. The severity of anaphylactic reaction is variable and can be classified into severity grades I-IV. Some reactions are fatal. Most frequent elicitors of anaphylaxis are foods in childhood, later insect stings and drugs. The phenomenon itself has been described in ancient medical literature, but was actually recognized and named at the beginning of the 20th century by Charles Richet and Paul Portier. In the course of experiments starting on the yacht of the Prince of Monaco and continued in the laboratory in Paris, they tried to immunize dogs with extracts of Physalia species in an attempt to develop an antitoxin to the venom of the Portuguese man-of-war. While Charles Richet believed that anaphylaxis was a 'lack of protection', it has become clear that an exaggerated immune reaction, especially involving immunoglobulin E antibodies, is the underlying pathomechanism in allergic anaphylaxis besides immune complex reactions. Non-immunologically mediated reactions leading to similar clinical symptomatology have been called 'anaphylactoid' or 'pseudo-allergic'--especially by Paul Kallos--and are now called 'non-immune anaphylaxis' according to a consensus of the World Allergy Organization (WAO). The distinction of different pathophysiological processes is important since non-immune anaphylaxis cannot be detected by skin test or in vitro allergy diagnostic procedures. History and provocation tests are crucial. The intensity of the reaction is not only influenced by the degree of sensitization but also by concomitant other factors as age, simultaneous exposure to other allergens, underlying infection, physical exercise or psychological stress or concomitant medication (e.g. beta-blockers, NSAIDs); this phenomenon has been called augmentation or summation anaphylaxis., (Copyright 2010 S. Karger AG, Basel.)

Background: In 2007, Australia implemented the National human papillomavirus (HPV) Vaccination Program, which provides quadrivalent HPV vaccine free to all women aged 12-26 years. Following notification of 7 presumptive cases of anaphylaxis in the state of New South Wales, Australia, we verified cases and compared the incidence of anaphylaxis following HPV vaccination to other vaccines in comparable settings., Methods: We contacted all patients with suspected anaphylaxis and obtained detailed histories from telephone interviews and a review of medical records. A multidisciplinary team determined whether each suspected case met the standardized Brighton definition. Some participants also received skin-prick allergy testing for common antigens and components of the HPV vaccine., Results: Of 12 suspected cases, 8 were classified as anaphylaxis. Of these, 4 participants had negative skin-prick test results for intradermal Gardasil. From the 269 680 HPV vaccine doses administered in schools, 7 cases of anaphylaxis were identified, which represents an incidence rate of 2.6 per 100 000 doses (95% CI 1.0-5.3 per 100 000). In comparison, the rate of identified anaphylaxis was 0.1 per 100 000 doses (95% CI 0.003-0.7) for conjugated meningococcal C vaccination in a 2003 school-based program., Interpretation: Based on the number of confirmed cases, the estimated rate of anaphylaxis following quadrivalent HPV vaccine was significantly higher than identified in comparable school-based delivery of other vaccines. However, overall rates were very low and managed appropriately with no serious sequelae.

The term "mastocytosis" denotes a heterogeneous group of disorders characterised by abnormal growth and accumulation of mast cells (MC) in one or more organ systems. Symptoms result from MC chemical mediator's release, pathologic infiltration of neoplastic MC in tissues or both. Multiple molecular, genetic and chromosomal defects seem to contribute to an autonomous growth, but somatic c-kit D816V mutation is more frequently encountered, especially in systemic disease. We present a literature review of mastocytosis and a rare case report of an 18 month-old-girl with a bullous dermatosis, respiratory distress and anaphylaxis, as clinical manifestations of mastocytosis. The developments of accepted classification systems and novel useful markers allowed a re-evaluation and updating of the classification of mastocytosis. In paediatric age cutaneous forms of disease prevail and may regress spontaneously. SM is more frequently diagnosed in adults and is a persistent (clonal) disease of bone marrow. The clinical course in these patients is variable. Today diagnostic criteria for each disease variant are reasonably well defined. There are, however, peculiarities, namely in paediatric age, that makes the diagnostic approach difficult. Systemic disease may pose differential diagnostic problems resulting from multiple organ systems involvement. Conversely, the "unexplained" appearance of those symptoms with no skin lesions should raise the suspicion of MC disease. This case is reported in order to stress the clinical severity and difficult diagnostic approach that paediatric mastocytosis may assume.

The present approach to the diagnosis, management and follow-up of anaphylaxis during anaesthesia varies in the Scandinavian countries. The main purpose of these Scandinavian Clinical Practice Guidelines is to increase the awareness about anaphylaxis during anaesthesia amongst anaesthesiologists. It is hoped that increased focus on the subject will lead to prompt diagnosis, rapid and correct treatment, and standardised management of patients with anaphylactic reactions during anaesthesia across Scandinavia. The recommendations are based on the best available evidence in the literature, which, owing to the rare and unforeseeable nature of anaphylaxis, mainly includes case series and expert opinion (grade of evidence IV and V). These guidelines include an overview of the epidemiology of anaphylactic reactions during anaesthesia. A treatment algorithm is suggested, with emphasis on the incremental titration of adrenaline (epinephrine) and fluid therapy as first-line treatment. Recommendations for primary and secondary follow-up are given, bearing in mind that there are variations in geography and resources in the different countries. A list of National Centres from which anaesthesiologists can seek advice concerning follow-up procedures is provided. In addition, an algorithm is included with advice on how to manage patients with previous suspected anaphylaxis during anaesthesia. Lastly, Appendix 2 provides an overview of the incidence, mechanisms and possibilities for follow-up for some common drug groups.

Hymenoptera are the large group of insects which includes honey-bees, bumble-bees, paper wasps, hornets, ants. Female hymenoptera possess specialized stinging apparatus with which they inject their venom into prey's or intruder's body. It could be life-threatening for people sensitive to the venom. The hymenoptera venom consists of mixture of biologically active substances, eg. enzymes (phospholipases, hialuronidase), peptides (melittin, apamin, mastoparans, bombolitins) and low-molecular-weight compounds (biogenic amines, acetylcholine, carbohydrates, lipids, free amino acids). Several types of reactions are possible to develop after stinging by hymenopteran insects: (1) non-allergic local reaction (pain, small oedema, redness at the site of the sting); allergic reactions: (2) large local reaction (extensive local swelling, exceeding 10 cm, persisting longer than 24 hours) and (3) anaphylaxis (generalized urticaria, bronchospasm, hypotension, cardiovascular collapse, loss of consciousness); (4) systemic toxic reaction (oedema, vomits, diarrhoea, headache, hypotension, seizures, altered mental status); (5) unusual reactions (cardiac ischaemia, encephalomyelitis et al.). Therapeutic management after stings includes removing of the stinger (bee stings), local remedies (ice-packs, topical steroids) and prevention and treatment of an anaphylactic shock (epinephrine, general steroids, beta-mimetics, fluid resuscitation, oxygen therapy). In the present review types of reaction after hymenoptera stings were described with special interest of anaphylactic and toxic reactions as well as therapeutic management after stings.

Objective: To examine the clinical characteristics of patients with anaphylactic reactions evaluated at the Puerto Rico Medical Center over a ten year period., Background: Anaphylaxis, an immunologic reaction classically initiated by the combination of an antigen and a mast cell fixed antibody (usually IgE), still carries a fatality rate of 500 to 1000 cases per year in the United States. It constitutes a medical emergency that needs to be identified promptly in order to install appropriate treatment. No studies of this condition have been conducted in Puerto Rico, specifically to assess the clinical presentation, main causes and outcome., Methods: Eighty-three records of patients with a diagnosis of anaphylaxis were screened by retrospective and concurrent analysis. Of these, only 51 fulfilled the diagnostic criteria of anaphylaxis. Specific data gathered from those records assessed the clinical characteristics of each case, precipitating factors, severity of the reaction and outcome. A standard form was used for data gathering. A grading system was utilized to classify the severity of the clinical episodes., Results: Cutaneous features were the most commonly found manifestations of anaphylactic reactions in the studied group. Only reactions graded 2 and 3 were identified. Reactions to medications were the most frequent identifiable causes of the entity. Multiple sensitivities to different allergens were not predictive of this clinical condition., Conclusions: The identification in this study that only cases with the more severe grades of anaphylaxis were evaluated and treated at our center, the inability to recognize an inciting cause in about one third of the patient sample and the fact that a minority of the treated patients received subsequent follow-up by an allergist, reflect the need to promote the training of physicians in the field of allergy in Puerto Rico and the continued education of all physicians in the Island regarding this clinical disorder.

Anaphylaxis is the maximal variant of an acute allergic reaction involving several organ systems. The phenomenon itself is old, but it was recognized and named at the beginning of the 20th century by Richet and Portier. The clinical symptoms of anaphylaxis affect various organs, most commonly starting in the skin and proceeding to the respiratory tract, to gastrointestinal involvement and to cardiovascular symptoms, and finally to cardiac and/or respiratory arrest. Anaphylaxis stricto sensu is an immunological reaction, mostly mediated by IgE antibodies, but also by IgG or IgM antibodies (immune complex anaphylaxis). There are cases with similar clinical symptomatology without detectable immunological sensitization which are called pseudo-allergic or anaphylactoid reactions. In the newer nomenclature, some authors tend to include these under the heading of 'anaphylaxis' which has then to be defined as an acute systemic hypersensitivity reaction. The most common elicitors of anaphylaxis include drugs, foods, additives, but also other allergens as well as physical factors (cold, heat, UV radiation). The clinical outcome--the intensity of the reaction--is not only influenced by the degree of sensitization, but also by concomitant other factors: sometimes, individuals only develop anaphylaxis after simultaneous exposure to the allergen and an infection, physical exercise, psychological stress or concomitant medication (e.g. beta blockers). The term 'summation anaphylaxis' has been proposed for this phenomenon which probably underlies many cases of so-called idiopathic anaphylaxis. In patients with insect venom anaphylaxis, decreased levels of plasma angiotensin have been measured in inverse correlation to the severity of the reaction. Certain differential diagnoses have to be distinguished from anaphylaxis. Every patient with a history of anaphylaxis should undergo allergy diagnosis with the aim to detect the eliciting agent, characterize the relevant pathomechanism (e.g. IgE-mediated reaction) and to offer a tolerable alternative (in food or drug allergy). In clear-cut IgE-mediated anaphylaxis, allergen-specific immunotherapy (hyposensitization) is the effective causal treatment, with success rates of 90% in insect venom anaphylaxis.

Anaphylaxis is a rarely anticipated, potentially life-threatening systemic allergic reaction with symptoms ranging from mild flushing to upper respiratory obstruction with or without vascular collapse. Early recognition of symptoms with prompt institution of therapy is central to a successful outcome. Anaphylaxis is IgE mediated, whereas non-IgE mediated anaphylatic reactions are termed anaphylactoid. Food-induced anaphylactic reactions, particularly peanut, are being recognized with increasing frequency. Central to appropriate therapy of the acute reaction is adminstration of intramuscular adrenalin. However, with the advent of humanized anti-IgE monoclonal antibody, such reactions may be reduced in frequency and severity.

Background: The jack jumper ant Myrmecia pilosula is responsible for about 90% of ant venom anaphylaxis in southeastern Australia. We aimed to establish whether M pilosula venom immunotherapy (VIT) prevents lifethreatening sting anaphylaxis in otherwise healthy adults., Methods: We did a double-blind, placebo-controlled crossover trial of M pilosula VIT. Participants were randomly allocated either immunotherapy, in accordance with the semirush hyposensitisation regimen, or placebo. The primary endpoint was systemic reaction after a deliberate sting challenge. Analysis was per protocol., Findings: We randomly allocated 68 healthy volunteers (aged 20-63 years) who were allergic to M pilosula venom to placebo (33) and VIT (35). Four on placebo were stopped early and 12 on VIT had their treatment allocations revealed before the sting challenge, thus 29 on placebo and 23 on VIT were included in the primary analysis. Objectively defined systemic reactions to sting challenges arose in 21 of 29 participants (72%) on placebo (8 reactions were associated with hypotension) and none of 23 on VIT (p<0.0001). Of the remaining 12 on VIT who underwent sting challenges after treatment allocations were revealed, only one reacted to sting challenge with transient urticaria that did not require treatment. After crossover of the placebo group to VIT, one of 26 had a reaction to sting challenge (transient urticaria). In all patients who had VIT, we recorded objective systemic reactions in 22 of 64 (34%) during VIT; two of which were hypotensive., Interpretation: In well motivated, highly allergic, but otherwise healthy adults, VIT is highly effective in prevention of M pilosula sting anaphylaxis. The risk of systemic reactions during VIT means that treatment should be given where there is immediate access to resuscitation facilities.

Background: Anaphylactoid reactions in anaesthesia are rare and should ideally be investigated in specialist centres. At Gentofte University Hospital, we established such a centre in 1998 as a joint venture between the Departments of Anaesthesiology and Dermatology. We present the methodology, diagnostic algorithm and preliminary results from our centre., Methods: We are open for referral of patients from all of Denmark. Reactions are classified using a three-grade severity scale and all reactions ranging from mild to severe are investigated. Investigations follow a standard step-by-step protocol of in vitro testing and skin testing. Blood samples for tryptase analysis are taken at the time of reaction and a control sample is taken together with samples for specific IgE analysis 2-4 weeks after the reaction. Subsequent skin testing comprises both prick tests and intradermal tests in most cases. Patients are tested with all substances they were exposed to, including antibiotics, colloids, latex and chlorhexidine., Results: A total of 68 patients have been referred to date (July 2001) and 36 have completed investigations. Positive test results were mainly seen in patients with more severe reactions, and there were more men than women in the group with the most severe reactions. Six patients had positive specific IgE, three for penicillin, two for latex and one for thiopental. In all, 21 patients had positive skin tests to various substances, of whom four men with anaphylactic shock tested positive for chlorhexidine. Only one patient has tested positive to a neuromuscular blocking drug (NMBD) so far., Discussion: Our preliminary results appear to differ in two ways from results usually found in this field. Firstly, only one patient has tested positive for a NMBD and secondly, we have had four patients with anaphylactic shock who have tested positive for chlorhexidine. Possible reasons for these differences are discussed.

The Gell and Coombs's classification divides drug allergies into four pathophysiological types, namely anaphylaxis (type I), antibody-mediated cytotoxic reactions (type II), immune complex-mediated reactions (type III), and delayed type hypersensitivity (type IV). Although this classification was proposed more than 30 years ago, it is still widely used. As only a limited number of drug allergies fit into this classification which does not include our current understanding of the immune response, its use is not recommended, particularly in the context of the preclinical safety evaluation of new therapeutic agents. In fact, three different situations can be identified, namely pseudo-allergic reactions, primarily antibody-mediated reactions and cell-mediated reactions, which could serve as a basis for modern and more adequate classifications