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Background: Anaphylaxis, which is rare, has been reported after COVID-19 vaccination, but its management is not standardized., Method: Members of the European Network for Drug Allergy and the European Academy of Allergy and Clinical Immunology interested in drug allergy participated in an online questionnaire on pre-vaccination screening and management of allergic reactions to COVID-19 vaccines, and literature was analysed., Results: No death due to anaphylaxis to COVID-19 vaccines has been confirmed in scientific literature. Potential allergens, polyethylene glycol (PEG), polysorbate and tromethamine are excipients. The authors propose allergy evaluation of persons with the following histories: 1-anaphylaxis to injectable drug or vaccine containing PEG or derivatives; 2-anaphylaxis to oral/topical PEG containing products; 3-recurrent anaphylaxis of unknown cause; 4-suspected or confirmed allergy to any mRNA vaccine; and 5-confirmed allergy to PEG or derivatives. We recommend a prick-to-prick skin test with the left-over solution in the suspected vaccine vial to avoid waste. Prick test panel should include PEG 4000 or 3500, PEG 2000 and polysorbate 80. The value of in vitro test is arguable., Conclusions: These recommendations will lead to a better knowledge of the management and mechanisms involved in anaphylaxis to COVID-19 vaccines and enable more people with history of allergy to be vaccinated., (© 2022 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Food anaphylaxis is commonly elicited by unintentional ingestion of foods containing the allergen above the tolerance threshold level of the individual. While labeling the 14 main allergens used as ingredients in food products is mandatory in the EU, there is no legal definition of declaring potential contaminants. Precautionary allergen labeling such as "may contain traces of" is often used. However, this is unsatisfactory for consumers as they get no information if the contamination is below their personal threshold. In discussions with the food industry and technologists, it was suggested to use a voluntary declaration indicating that all declared contaminants are below a threshold of 0.5 mg protein per 100 g of food. This concentration is known to be below the threshold of most patients, and it can be technically guaranteed in most food production. However, it was also important to assess that in case of accidental ingestion of contaminants below this threshold by highly allergic patients, no fatal anaphylactic reaction could occur. Therefore, we performed a systematic review to assess whether a fatal reaction to 5mg of protein or less has been reported, assuming that a maximum portion size of 1kg of a processed food exceeds any meal and thus gives a sufficient safety margin., Methods: MEDLINE and EMBASE were searched until 24 January 2021 for provocation studies and case reports in which one of the 14 major food allergens was reported to elicit fatal or life-threatening anaphylactic reactions and assessed if these occurred below the ingestion of 5mg of protein. A Delphi process was performed to obtain an expert consensus on the results., Results: In the 210 studies included, in our search, no reports of fatal anaphylactic reactions reported below 5 mg protein ingested were identified. However, in provocation studies and case reports, severe reactions below 5 mg were reported for the following allergens: eggs, fish, lupin, milk, nuts, peanuts, soy, and sesame seeds., Conclusion: Based on the literature studied for this review, it can be stated that cross-contamination of the 14 major food allergens below 0.5 mg/100 g is likely not to endanger most food allergic patients when a standard portion of food is consumed. We propose to use the statement "this product contains the named allergens in the list of ingredients, it may contain traces of other contaminations (to be named, e.g. nut) at concentrations less than 0.5 mg per 100 g of this product" for a voluntary declaration on processed food packages. This level of avoidance of cross-contaminations can be achieved technically for most processed foods, and the statement would be a clear and helpful message to the consumers. However, it is clearly acknowledged that a voluntary declaration is only a first step to a legally binding solution. For this, further research on threshold levels is encouraged., (© 2021 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Chemotherapeutic drugs have been widely used in the treatment of cancer disease for about 70 years. The development of new treatments has not hindered their use, and oncologists still prescribe them routinely, alone or in combination with other antineoplastic agents. However, all chemotherapeutic agents can induce hypersensitivity reactions (HSRs), with different incidences depending on the culprit drug. These reactions are the third leading cause of fatal drug-induced anaphylaxis in the United States. In Europe, deaths related to chemotherapy have also been reported. In particular, most reactions are caused by platinum compounds, taxanes, epipodophyllotoxins and asparaginase. Despite their prevalence and relevance, the ideal pathways for diagnosis, treatment and prevention of these reactions are still unclear, and practice remains considerably heterogeneous with vast differences from center to center. Thus, the European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology organized a task force to provide data and recommendations regarding the allergological work-up in this field of drug hypersensitivity reactions. This position paper aims to provide consensus on the investigation of HSRs to chemotherapeutic drugs and give practical recommendations for clinicians that treat these patients, such as oncologists, allergologists and internists. Key sections cover risk factors, pathogenesis, symptoms, the role of skin tests, in vitro tests, indications and contraindications of drug provocation tests and desensitization of neoplastic patients with allergic reactions to chemotherapeutic drugs. Statements, recommendations and unmet needs were discussed and proposed at the end of each section., (© 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Mobile health (mHealth) uses mobile communication devices such as smartphones and tablet computers to support and improve health-related services, data and information flow, patient self-management, surveillance, and disease management from the moment of first diagnosis to an optimized treatment. The European Academy of Allergy and Clinical Immunology created a task force to assess the state of the art and future potential of mHealth in allergology. The task force endorsed the "Be He@lthy, Be Mobile" WHO initiative and debated the quality, usability, efficiency, advantages, limitations, and risks of mobile solutions for allergic diseases. The results are summarized in this position paper, analyzing also the regulatory background with regard to the "General Data Protection Regulation" and Medical Directives of the European Community. The task force assessed the design, user engagement, content, potential of inducing behavioral change, credibility/accountability, and privacy policies of mHealth products. The perspectives of healthcare professionals and allergic patients are discussed, underlining the need of thorough investigation for an effective design of mHealth technologies as auxiliary tools to improve quality of care. Within the context of precision medicine, these could facilitate the change in perspective from clinician- to patient-centered care. The current and future potential of mHealth is then examined for specific areas of allergology, including allergic rhinitis, aerobiology, allergen immunotherapy, asthma, dermatological diseases, food allergies, anaphylaxis, insect venom, and drug allergy. The impact of mobile technologies and associated big data sets are outlined. Facts and recommendations for future mHealth initiatives within EAACI are listed., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Proton pump inhibitors (PPIs) are invaluable therapeutic options in a variety of dyspeptic diseases. In addition to their well‐known risk profile, PPI consumption is related to food and environmental allergies, dysbiosis, osteoporosis, as well as immediate and delayed hypersensitivity reactions (HSRs). The latter, although a rare event, around 1%–3%, due to the extraordinarily high rate of prescription and consumption of PPIs are related to a substantial risk. In this Position Paper, we provide clinicians with practical evidence‐based recommendations for the diagnosis and management of HSRs to PPIs. Furthermore, the unmet needs proposed in the document aim to stimulate more in‐depth investigations in the topic. [ABSTRACT FROM AUTHOR]

Drug allergy (DA) remains a complex and unaddressed problem worldwide that often deprives patients of optimal medication choices and places them at risk for life-threatening reactions. Underdiagnosis and overdiagnosis are common and due to the lack of standardized definitions and biomarkers. The true burden of DA is unknown, and recent efforts in data gathering through electronic medical records are starting to provide emerging patterns around the world. Ten percent of the general population engaged in health care claim to have a DA, and the most common label is penicillin allergy. Up to 20% of emergency room visits for anaphylaxis are due to DA and 15%-20% of hospitalized patients report DA. It is estimated that DA will increase based on the availability and use of new and targeted antibiotics, vaccines, chemotherapies, biologicals, and small molecules, which are aimed at improving patient's options and quality of life. Global and regional variations in the prevalence of diseases such as human immunodeficiency virus and mycobacterial diseases, and the drugs used to treat these infections have an impact on DA. The aim of this review is to provide an update on the global impact of DA by presenting emerging data on drug epidemiology in adult and pediatric populations., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Anaphylaxis is a growing paediatric clinical emergency that is difficult to diagnose because a consensus definition was lacking until recently. Many European countries have no specific guidelines for anaphylaxis. This position paper prepared by the EAACI Taskforce on Anaphylaxis in Children aims to provide practical guidelines for managing anaphylaxis in childhood based on the limited evidence available. Intramuscular adrenaline is the acknowledged first-line therapy for anaphylaxis, in hospital and in the community, and should be given as soon as the condition is recognized. Additional therapies such as volume support, nebulized bronchodilators, antihistamines or corticosteroids are supplementary to adrenaline. There are no absolute contraindications to administering adrenaline in children. Allergy assessment is mandatory in all children with a history of anaphylaxis because it is essential to identify and avoid the allergen to prevent its recurrence. A tailored anaphylaxis management plan is needed, based on an individual risk assessment, which is influenced by the child's previous allergic reactions, other medical conditions and social circumstances. Collaborative partnerships should be established, involving school staff, healthcare professionals and patients' organizations. Absolute indications for prescribing self-injectable adrenaline are prior cardiorespiratory reactions, exercise-induced anaphylaxis, idiopathic anaphylaxis and persistent asthma with food allergy. Relative indications include peanut or tree nut allergy, reactions to small quantities of a given food, food allergy in teenagers and living far away from a medical facility. The creation of national and European databases is expected to generate better-quality data and help develop a stepwise approach for a better management of paediatric anaphylaxis.

Background: Drugs are a frequent cause of severe anaphylactic reactions. Here, we analyze a large dataset on drug induced anaphylaxis regarding elicitors, risk factors, symptoms, and treatment., Methods: Data from the European Anaphylaxis Registry (2007-2019) with 1815 reported cases of drug-induced anaphylaxis were studied accordingly., Results: Drugs are the third most frequent cause of anaphylaxis reported in the Anaphylaxis Registry. Among the eliciting groups of drugs analgesics and antibiotics were far most often reported. Female and senior patients were more frequently affected, while the number of children with DIA was low. DIA patients had symptoms affecting the skin and mucous membranes (n = 1525, 84.02%), the respiratory (n = 1300, 71.63%), the cardiovascular (n = 1251, 68.93%) and the gastrointestinal system (n = 549, 30.25%). Drugs caused significant more severe reactions, occurred more often in medical facilities and led to increased hospitalization rates in comparison to food and insect venom induced anaphylaxis. Adrenaline was used more often in patients with DIA than in anaphylaxis due to other causes. Patients with skin symptoms received more antihistamines and corticosteroids in the acute treatment, while gastrointestinal symptoms led to less adrenaline use., Conclusion: The study contributes to a better understanding of DIA, with a large number of cases from Europe supporting previous data, e.g., analgesics and antibiotics being the most frequent culprits for DIA. Female gender and higher age are relevant risk factors and despite clear recommendations, the emergency treatment of DIA is not administered according to the guidelines., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Immunotherapy with Hymenoptera venoms is widely used throughout the world and is accepted as an effective treatment for most patients with Hymenoptera venom allergy. There are, however, still some unresolved problems with this form of treatment. At present there is no definite test which makes it possible to identify patients at risk - and thus candidates for immunotherapy - unequivocally. On the basis of prospective studies on the natural history of Hymenoptera allergy, venom immunotherapy is indicated in adults with severe systemic anaphylaxis. It is usually not necessary in patients with large local reactions only. Children with mild systemic reactions, e.g. urticaria, will need immunotherapy only in case of repeated reactions and/or a high risk of re-exposure. The selection of venoms for immunotherapy may lead to some confusion owing to common antigenic determinants shared by venoms of various Hymenoptera species. Many different regimens for immunotherapy have been proposed. At present, the three main are: rush, stepwise or clustered and classical. The maintenance dose of 100 micrograms usually protects from life-threatening reactions. However, in some patients 200 micrograms are necessary for complete protection. The usual interval between maintenance injections is 4 to 6 weeks. In many patients a strong increase of venom specific serum IgG-antibodies usually parallels clinical protection induced by venom immunotherapy, although many exceptions have been reported. Allergic side effects of venom immunotherapy are not rare, especially with honey bee venom and during the initial phase of dose increase. The question of the duration of venom immunotherapy is handled differently: although some authors recommend treatment for life, most suggest treating patients until skin tests and RAST become negative.

Background: The coronavirus disease 2019 (COVID‐19) has evolved into a pandemic infectious disease transmitted by the severe acute respiratory syndrome coronavirus (SARS‐CoV‐2). Allergists and other healthcare providers (HCPs) in the field of allergies and associated airway diseases are on the front line, taking care of patients potentially infected with SARS‐CoV‐2. Hence, strategies and practices to minimize risks of infection for both HCPs and treated patients have to be developed and followed by allergy clinics. Method: The scientific information on COVID‐19 was analysed by a literature search in MEDLINE, PubMed, the National and International Guidelines from the European Academy of Allergy and Clinical Immunology (EAACI), the Cochrane Library, and the internet. Results: Based on the diagnostic and treatment standards developed by EAACI, on international information regarding COVID‐19, on guidelines of the World Health Organization (WHO) and other international organizations, and on previous experience, a panel of experts including clinicians, psychologists, IT experts, and basic scientists along with EAACI and the "Allergic Rhinitis and its Impact on Asthma (ARIA)" initiative have developed recommendations for the optimal management of allergy clinics during the current COVID‐19 pandemic. These recommendations are grouped into nine sections on different relevant aspects for the care of patients with allergies. Conclusions: This international Position Paper provides recommendations on operational plans and procedures to maintain high standards in the daily clinical care of allergic patients while ensuring the necessary safety measures in the current COVID‐19 pandemic. [ABSTRACT FROM AUTHOR]

Anaphylaxis is a clinical emergency which all healthcare professionals need to be able to recognize and manage. The European Academy of Allergy and Clinical Immunology Anaphylaxis multidisciplinary Task Force has updated the 2014 guideline. The guideline was developed using the AGREE II framework and the GRADE approach. The evidence was systematically reviewed and recommendations were created by weighing up benefits and harms. The guideline was peer-reviewed by external experts and reviewed in a public consultation. The use of clinical criteria to identify anaphylaxis is suggested with blood sampling for the later measurement of tryptase. The prompt use of intramuscular adrenaline as first-line management is recommended with the availability of adrenaline autoinjectors to patients in the community. Pharmacokinetic data should be provided for adrenaline autoinjector devices. Structured, comprehensive training for people at risk of anaphylaxis is recommended. Simulation training and visual prompts for healthcare professionals are suggested to improve the management of anaphylaxis. It is suggested that school policies reflect anaphylaxis guidelines. The evidence for the management of anaphylaxis remains mostly at a very low level. There is an urgent need to prioritize clinical trials with the potential to improve the management of patients at risk of anaphylaxis., (© 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Amoxicillin (AX) combined or not with clavulanic acid (CLV) is frequently involved in IgE-mediated reactions. Drug provocation test (DPT) is considered as the gold standard for diagnosis, although contraindicated in high-risk patients. Basophil activation test (BAT) can help diagnose immediate reactions to beta-lactams, although controversy exists regarding the best activation marker. We have performed a real-life study in a prospective cohort to analyze the real value of BAT as diagnostic tool and the best activation marker, CD63 and CD203c, for the evaluation of immediate reactions to these drugs., Methods: We prospectively evaluated patients with a clinical suspicion of immediate reactions after AX or AX-CLV administration during a 6-year period. The allergological work-up was done following the EAACI recommendations. BAT was performed in all patients using CD63 and CD203c as activation markers., Results: In AX-allergic patients, both activation markers, CD63 and CD203c, showed similar SE values (48.6% and 46.7%, respectively); however, specificity was of 81.1% and 94.6%, respectively, with CD203c showing good positive predictive value and like-hood ratio. In CLV-allergic patients, CD203c showed higher SE (50%) than CD63 (42.9%), maintaining the same value of SP (80%). Combining the results of both markers can slightly increase the sensitivity (51.4% for AX and 54.8% for CLV), although decreasing the specificity (79.7% and 73%, respectively). Interestingly, all patients with an anaphylactic shock showed a positive BAT to CLV using CD203c., Conclusions: BAT using CD203c showed a good confirmatory power, especially for AX allergy. Placing BAT as a first step in the diagnostic procedure can help reduce the need of performing a complete allergological work-up in 46.6% of patients, diminishing the risk of reinducing allergic reactions., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Further to the approval of the Coronavirus disease 2019 (COVID‐19) vaccine BNT162b2, several severe anaphylaxis cases occured within the first few days of public vaccination. An investigation is taking place to understand the cases and their triggers. The vaccine will be administered to a large number of individuals worldwide and there are raising concerns that severe adverse events might occur. With the current information, the European Academy of Allergy and Clinical Immunology (EAACI) states its position for the following preliminary recommendations that are to be revised as soon as more data emerge. To minimize the risk of severe allergic reactions in vaccinated individuals, it is urgently required to understand the specific nature of the reported severe allergic reactions, including the background medical history of the individuals affected and the mechanisms involved. To achieve this goal, all clinical and laboratory information should be collected and reported. Mild and moderate allergic patients should not be excluded from the vaccine as this could have a significant impact on reaching the goal of population immunity. Healthcare practitioners vaccinating against COVID‐19 are required to be sufficiently prepared to recognize and treat anaphylaxis properly with the ability to administer adrenaline. Further to vaccine administration, a mandatory observation period of at least 15 minutes should be followed for all individuals. The current data have not shown any higher risk for patients suffering from allergic rhinitis or asthma, and this message should be clearly stated by physicians to enable our patients to trust the vaccine. More than 30% of the population suffers from allergic diseases and the benefit of the vaccination clearly outweighs the risk of severe COVID‐19 development. [ABSTRACT FROM AUTHOR]

Perioperative immediate hypersensitivity reactions are rare. Subsequent allergy investigation is complicated by multiple simultaneous drug exposures, the use of drugs with potent effects and the many differential diagnoses to hypersensitivity in the perioperative setting. The approach to the investigation of these complex reactions is not standardized, and it is becoming increasingly apparent that collaboration between experts in the field of allergy/immunology/dermatology and anaesthesiology is needed to provide the best possible care for these patients. The EAACI task force behind this position paper has therefore combined the expertise of allergists, immunologists and anaesthesiologists. The aims of this position paper were to provide recommendations for the investigation of immediate‐type perioperative hypersensitivity reactions and to provide practical information that can assist clinicians in planning and carrying out investigations. [ABSTRACT FROM AUTHOR]

Background: Epinephrine is the first-line treatment for anaphylaxis. Patients at risk should always carry an epinephrine autoinjector (EAI). Several EAI gaps have been identified. We sought to evaluate satisfaction using a medical device (digital technology comprising an EAI smart case connected to a mobile APP) with functions that overcome most of the EAI limitations and to determine whether patient behaviour and anaphylaxis management improve with its use., Methods: This was a randomized, open-label, crossover clinical trial in a tertiary hospital involving patients with history of anaphylaxis carrying an EAI. The study was conducted in two three-month periods, one with and one without the medical device. The primary endpoint was satisfaction with the medical device. Usability, adherence, anxiety and anaphylaxis episodes were evaluated as secondary endpoints., Results: A total of 100 patients were included (mean age 38.1 years, 74% female), and 95 completed the trial. The satisfaction visual analogue scale (VAS) after using the medical device was higher than before its use (89.1 [95% CI, 60.2-99.1] vs 56.3 [95% CI, 48.1-81.4]; P < .0001). The adherence VAS improved from 59.7 (95% CI, 54.0-65.3) to 88.6 (95% CI, 84.2-92.9) (P < .0001). Overall, 90% patients found the medical device easy to use. Patients' anxiety decreased from 52.2% to 29.3% (P < .001). Seven episodes of anaphylaxis occurred during the study, all in patients without the medical device (P = .025). Eighty-eight per cent of patients felt more involved in the management of anaphylaxis when using the medical device., Conclusion: This is the first clinical trial evaluating digital technology for EAIs, showing a change of behaviour in patients at risk of anaphylaxis, increasing satisfaction, improving adherence, and reducing anxiety, with good usability., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

The International Classification of Diseases (ICD) provides a common language for use worldwide as a diagnostic and classification tool for epidemiology, clinical purposes and health management. Since its first edition, the ICD has maintained a framework distributing conditions according to topography, with the result that some complex conditions, such as allergies and hypersensitivity disorders (A/H) including anaphylaxis, have been poorly represented. The change in hierarchy in ICD-11 permitted the construction of the pioneer section addressed to A/H, which may result in more accurate mortality and morbidity statistics, including more accurate accounting for mortality due to anaphylaxis, strengthen classification, terminology and definitions. The ICD-11 was presented and adopted by the 72nd World Health Assembly in May 2019, and the implementation is ongoing worldwide. We here present the outcomes from an online survey undertaken to reach out the allergy community worldwide in order to peer review the terminology, classification and definitions of A/H introduced into ICD-11 and to support their global implementation. Data are presented here for 406 respondents from 74 countries. All of the subsections of the new A/H section of the ICD-11 had been considered with good accuracy by the majority of respondents. We believe that, in addition to help during the implementation phase, all the comments provided will help to improve the A/H classification and to increase awareness by different disciplines of what actions are needed to ensure more accurate epidemiological data and better clinical management of A/H patients., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Evaluation of perioperative hypersensitivity (POH) is challenging, and accurate screening tools are needed to optimize the diagnostic process. We aimed to assess and validate the diagnostic value of a published algorithm (using tryptase and clinical presentation) to identify appropriate individuals for further testing for IgE-mediated POH., Methods: We analysed the clinical presentation (tryptase elevation, cardiovascular, respiratory, skin involvement) of patients proceeding to testing for possible IgE-mediated POH at a single tertiary referral centre, relative to subsequent skin testing and specific IgE results. Clinical presentations by drug class were also determined., Results: In 293 consecutive patients, the use of a published algorithm based on one or more of; (i) defined increase in serum tryptase, (ii) involvement of at least two-organ systems, or (iii) presentation with new urticaria and/or angioedema; was highly sensitive [98.8% (CI95: 95.7-99.9%)] but less specific [34.6% (CI95: 25.7-44.4%)] in identifying patients testing positive on skin testing and/or specific IgE. Presentation with cardiovascular symptoms was also sensitive [89.8%(CI95: 84.2-94.0%)], while the combination of respiratory symptoms and increased tryptase was most specific [85.9%(CI95:76.6-92.5%)]. Respiratory involvement was more common in neuromuscular blocking agent allergy, while urticaria/angioedema was more common in antibiotic allergy., Conclusion: The published algorithm (of tryptase rise, two-organ involvement or new urticaria/angioedema) is highly sensitive, and appropriate as a screening tool to identify patients suitable for testing for IgE-mediated POH., (© 2022 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Immunoglobulin E is the latest discovered of immunoglobulin family and has been long associated with anaphylaxis and worm expulsion. Immunoglobulin E, along with mast cells, basophils, and eosinophils, is also a hallmark of type 2 immunity which is dysregulated in numerous diseases such as asthma, rhinitis, atopic dermatitis, and eosinophilic esophagitis in addition to anaphylaxis as aforementioned. However, recent advances have shed light on IgE regulation and memory explaining the low level of free IgE, the scarcity of IgE plasma cells that are mainly short live and the absence of IgE memory B cells in homeostatic conditions. Furthermore, IgE was implicated in inflammatory conditions beyond allergic disorders where IgE-mediated facilitated antigen presentation can enhance cellular and humoral response against autoantigens in systemic lupus or chronic urticaria leading to more severe disease and even against neoantigen facilitating tumor cell lysis. At last, IgE was unexpectedly associated with allograft rejection or atheromatous cardiovascular diseases where precise mechanisms remain to be deciphered. The purpose of this review is to summarize these recent advances in IgE regulation, biology, and physiopathology beyond allergic diseases opening whole new fields of IgE biology to explore., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: The European Academy of Allergy and Clinical Immunology has developed a guideline to provide evidence-based recommendations for healthcare professionals to support the transitional care of adolescents and young adults (AYA) with allergy and/or asthma. The goal of this work was to ensure that the draft recommendations are also important for patients., Methods: We surveyed patients aged 11-25 years with allergy and/or asthma and their parents across Europe between 17 February and 16 March 2020. The multilingual survey was distributed through national allergy and asthma patient organizations in Europe as well as through social media., Results: A total of 1210 responses from 24 European countries were collected. There were 415 (34.3%) AYA and 795 (65.7%) parents. The majority of AYA (72.3%) and parents (81.9%) were female. Patients had a history of asthma (61.1%), allergic rhinoconjunctivitis (54.1%), food allergy (53.8%), atopic eczema (42.6%) and anaphylaxis (28.8%). All recommendations achieved the median score of either 'important' or 'very important'. The least supported recommendations were the use of joint clinics with both paediatric and adult physicians attending and the use of web-based or mobile technologies for communication with the AYA. The most supported recommendation was checking that the AYA is knowledgeable and compliant with their prescribed medication. Qualitative analysis revealed conditional approval for some recommendations., Conclusions: There was agreement from patients and parents on the importance of the draft recommendations on transitional care for AYA with allergy and/or asthma and their parents. The recommendations now need to be implemented into clinical practice across Europe., (© 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Hymenoptera venom allergy ranks among the top three causes of anaphylaxis worldwide, and approximately one-quarter of sting-induced reactions are classified as severe. Fatal sting reactions are exceedingly rare, but certain factors may entail a considerably higher risk. Delayed administration of epinephrine and upright posture are situational risk factors which may determine an unfavorable outcome of the acute anaphylactic episode and should be addressed during individual patient education. Systemic mastocytosis and senior age are major, unmodifiable long-term risk factors and thus reinforce the indication for venom immunotherapy. Vespid venom allergy and male sex likewise augment the risk of severe or even fatal reactions. Further studies are required to assess the impact of specific cardiovascular comorbidities. Available data regarding potential effects of beta-blockers and/or ACE inhibitors in coexisting venom allergy are inconclusive and do not justify recommendations to discontinue guideline-directed antihypertensive treatment. The absence of urticaria/angioedema during sting-induced anaphylaxis is indicative of a severe reaction, serum tryptase elevation, and mast cell clonality. Determination of basal serum tryptase levels is an established diagnostic tool for risk assessment in Hymenoptera venom-allergic patients. Measurement of platelet-activating factor acetylhydrolase activity represents a complementary approach but is not available for routine diagnostic use., (© 2020 EAACI and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background Hymenoptera stings can cause severe anaphylaxis in untreated venom-allergic patients. A correct diagnosis regarding the relevant species for immunotherapy is often hampered by clinically irrelevant cross-reactivity. In vespid venom allergy, cross-reactivity between venoms of different species can be a diagnostic challenge. To address immunological IgE cross-reactivity on molecular level, seven recombinant antigens 5 of the most important Vespoidea groups were assessed by different diagnostic setups. Methods The antigens 5 of yellow jackets, hornets, European and American paper wasps, fire ants, white-faced hornets, and Polybia wasps were recombinantly produced in insect cells, immunologically and structurally characterized, and their sIgE reactivity assessed by Immuno CAP, ELISA, cross-inhibition, and basophil activation test ( BAT) in patients with yellow jacket or Polistes venom allergy of two European geographical areas. Results All recombinant allergens were correctly folded and structural models and patient reactivity profiles suggested the presence of conserved and unique B-cell epitopes. All antigens 5 showed extensive cross-reactivity in sIgE analyses, inhibition assays, and BAT. This cross-reactivity was more pronounced in Immuno CAP measurements with venom extracts than in sIgE analyses with recombinant antigens 5. Dose-response curves with the allergens in BAT allowed a differentiated individual dissection of relevant sensitization. Conclusions Due to extensive cross-reactivity in various diagnostic settings, antigens 5 are inappropriate markers for differential sIgE diagnostics in vespid venom allergy. However, the newly available antigens 5 from further vespid species and the combination of recombinant allergen-based sIgE measurements with BAT represents a practicable way to diagnose clinically relevant sensitization in vespid venom allergy. [ABSTRACT FROM AUTHOR]

The article presents the case study of a 81 year old woman who showed symptoms of grade III anaphylaxis with palmar pruritus, lips swelling and hypotension. She reportedly used a new toilet paper comprising of polyhexanide as disinfectant. She had a history of similar allergies and was unaware of such allergies and atopic disease. She underwent several skin prick tests (SPT) whose result was positive. The article discusses the role of polyhexanide as antiseptic used in wound dressing.

Insect venom allergy is the most frequent cause of anaphylaxis in Europe and possibly worldwide. The majority of systemic allergic reactions after insect stings are caused by Hymenoptera, and among these, vespid genera induce most of the systemic sting reactions (SSR). Honey bees are the second leading cause of SSR. Depending on the global region, other Hymenoptera such as different ant genera are responsible for SSR. Widely distributed hornets and bumblebees or local vespid or bee genera rarely induce SSR. Hematophagous insects such as mosquitoes and horse flies usually cause (large) local reactions while SSR occasionally occur. This position paper aimed to identify either rare or locally important insects causing SSR as well as rarely occurring SSR after stings or bites of widely distributed insects. We summarized relevant venom or saliva allergens and intended to identify possible cross-reactivities between the insect allergens. Moreover, we aimed to locate diagnostic tests for research and routine diagnosis, which are sometimes only regionally available. Finally, we gathered information on available immunotherapies. Major allergens of most insects were identified, and cross-reactivity between insects was frequently observed. While some diagnostics and immunotherapies are locally available, standardized skin tests and immunotherapies are generally lacking in rare insect allergy., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Conjunctival allergen provocation test ( CAPT) reproduces the events occurring by instilling an allergen on the ocular surface. This paper is the compilation of a task force focussed on practical aspects of this technique based on the analysis of 131 papers. Main mechanisms involved are reviewed. Indications are diagnosing the allergen(s)-triggering symptoms in IgE-mediated ocular allergy in seasonal, acute or perennial forms of allergic conjunctivitis, especially when the relevance of the allergen is not obvious or in polysensitized patients. Contraindications are limited to ongoing systemic severe pathology, asthma and eye diseases. CAPT should be delayed if receiving systemic steroids or antihistamines. Local treatment should be interrupted according to the half-life of each drug. Prerequisites are as follows: obtaining informed consent; evidencing of an allergen by skin prick tests and/or serum-specific IgE dosages; being able to deal with an unlikely event such as acute asthma exacerbation, urticaria or anaphylaxis, or an exacerbation of allergic conjunctivitis. Allergen extracts should be diluted locally prior to administration. Positive criteria are based on itching or quoted according to a composite score. An alternative scoring is based on itching. CAPT remains underused in daily practice, although it is a safe and simple procedure which can provide valuable clinical information. [ABSTRACT FROM AUTHOR]

A markedly decreased PAF-AH activity was found in the only HVA patient with asthma (PAF-AH: 10.9 nmol/mL/min). Keywords: anaphylaxis; asthma; biomarkers; Hymenoptera venom allergy; platelet-activating factor acetylhydrolase EN anaphylaxis asthma biomarkers Hymenoptera venom allergy platelet-activating factor acetylhydrolase 1032 1035 4 03/02/22 20220301 NES 220301 ACKNOWLEDGMENTS The authors would like to thank Valerio Pravettoni for his contribution to the discussion of the results of the paper. However, since PAF-AH values in the HVA population were lower than those of the control groups, we can assume that PAF-AH was able to characterize HVA patients as a separate population from healthy subjects and patients with allergic asthma and/or rhinitis. [Extracted from the article]

Allergic diseases of the (upper and lower) airways, the skin and the gastrointestinal tract, are on the rise, resulting in impaired quality of life, decreased productivity, and increased healthcare costs. As allergic diseases are mostly tissue‐specific, local sampling methods for respective biomarkers offer the potential for increased sensitivity and specificity. Additionally, local sampling using noninvasive or minimally invasive methods can be cost‐effective and well tolerated, which may even be suitable for primary or home care sampling. Non‐ or minimally invasive local sampling and diagnostics may enable a more thorough endotyping, may help to avoid under‐ or overdiagnosis, and may provide the possibility to approach precision prevention, due to early diagnosis of these local diseases even before they get systemically manifested and detectable. At the same time, dried blood samples may help to facilitate minimal‐invasive primary or home care sampling for classical systemic diagnostic approaches. This EAACI position paper contains a thorough review of the various technologies in allergy diagnosis available on the market, which analytes or biomarkers are employed, and which samples or matrices can be used. Based on this assessment, EAACI position is to drive these developments to efficiently identify allergy and possibly later also viral epidemics and take advantage of comprehensive knowledge to initiate preventions and treatments. [ABSTRACT FROM AUTHOR]

J Reprod Immunol. 2018; 128: 30 - 37. 15 Francuzik W, Nassiri M, Babina M, Worm M. Impact of sex on anaphylaxis severity - Data from the anaphylaxis registry. Anaphylaxis, drug allergy, epidemiology Anaesthesia, surgery, and life-threatening allergic reactions: epidemiology and clinical features of perioperative anaphylaxis in the 6th National Audit Project (NAP6). Keywords: anaphylaxis; drug allergy; epidemiology EN anaphylaxis drug allergy epidemiology 1317 1319 3 03/30/22 20220401 NES 220401 ACKNOWLEDGEMENTS The authors would like to thank Dr. Erik Florvaag for his input in the process of writing this paper. [Extracted from the article]

Background: Despite an increasing number of publications from individual countries and regions, there is still no systematic review of the global epidemiology of anaphylaxis in the general paediatric population., Methods: We conducted a systematic review, using a protocol registered and published with the international prospective register of systematic reviews (PROSPERO). Results were reported following PRISMA guidelines. The search strategy was designed in Medline (ovid) and modified for Embase (ovid) and PubMed. Papers were screened by two independent reviewers following selection and exclusion criteria. Data extraction and risk of bias assessment were completed by the same two reviewers. Studies in adults only or those that did not report data in children separately were excluded., Results: A final total of 59 articles were included. Of these, 5 reported cumulative incidence, 39 reported incidence rate and 17 reported prevalence data. The incidence of anaphylaxis in children worldwide varied widely, ranging from 1 to 761 per 100 000 person-years for total anaphylaxis and 1 to 77 per 100 000 person-years for food-induced anaphylaxis. The definition of anaphylaxis from NIAID/FAAN was the most commonly used. Gender and ethnicity were demographic risk factors associated with anaphylaxis in children. Increasing total or food-induced anaphylaxis incidence over time was reported by 19 studies., Conclusion: The reported incidence of anaphylaxis in children varied widely. Studies in developing countries are underrepresented. To accurately compare anaphylaxis incidence between countries and investigate the time trends, further studies using a standardized definition across different countries are required., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Anaphylaxis, food allergy, shrimp allergy, shrimp oral immunotherapy, tropomyosin Keywords: anaphylaxis; food allergy; shrimp allergy; shrimp oral immunotherapy; tropomyosin EN anaphylaxis food allergy shrimp allergy shrimp oral immunotherapy tropomyosin 2825 2829 5 09/02/22 20220901 NES 220901 Abbreviations Der f1 Dermatophagoides farinae Der p1 Dermatophagoides pteronyssinus rPen a recombinant Penaeus aztecus rPen m recombinant Penaeus monodon SA shrimp allergy sIgE specific IgE ACKNOWLEDGMENT We acknowledge funding from the National Institute of Allergy and Infectious Disease for this work. [Extracted from the article]

Until now, immunoassays for detection of anti-muscle relaxant IgE in serum have been performed with the drug coupled to epoxy-activated Sepharose or to RAST papers dies. In the present work we have used a quaternary ammonium-Sepharose in which the quaternary ammonium reactive group (choline chloride) was directly coupled to Sepharose via an ether linkage. 50 μl of the quaternary ammonium solid phase (QAS) was incubated with 50 μl of serum for 3 h, washed, incubated 18 h with 125I-anti-IgE and washed again. The results were expressed as the percentage of 125I-anti-IgE adsorbed onto the solid phase. The results were at 1.3±0.5% for 20 control sera, with an upper normal limit estimated to 2.3%. The within-run reproducibility ranged from 3.2% to 10.0%. The results were significantly correlated with those obtained with either alcuroniumepoxy-Sepharosc, choline-epoxy-Sepharose, the RAST-alcuronium or with the RAST-succinyl choline (respectively, r = 0.66, r = 0.80, r = 0.81, r = 0.40 and r = 0.85). The values obtained with the sera of 83 patients ranged from 0.3 to 38.5%. The sensitivity was estimated at 87,9%, 66.7% and 40.7% with the QAS-RIA, the RAST-succinyl choline and the RAST-alcuronium, respectively. The inhibition of adsorption of specific IgE onto the gel ranged from 13.0 to 90.6% in presence of 130 nmol of soluble muscle relaxants. In 83.3% of 30 cases, the highest inhibition was obtained with the muscle relaxant which was clinically incriminated. In conclusion, the reactive-solid phase which was used in the present work significantly increased the sensitivity of detection of anti-muscle relaxant IgE in serum. [ABSTRACT FROM AUTHOR]

Food allergy can result in considerable morbidity, impact negatively on quality of life, and prove costly in terms of medical care. These guidelines have been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Guidelines for Food Allergy and Anaphylaxis Group, building on previous EAACI position papers on adverse reaction to foods and three recent systematic reviews on the epidemiology, diagnosis, and management of food allergy, and provide evidence-based recommendations for the diagnosis and management of food allergy. While the primary audience is allergists, this document is relevant for all other healthcare professionals, including primary care physicians, and pediatric and adult specialists, dieticians, pharmacists and paramedics. Our current understanding of the manifestations of food allergy, the role of diagnostic tests, and the effective management of patients of all ages with food allergy is presented. The acute management of non-life-threatening reactions is covered in these guidelines, but for guidance on the emergency management of anaphylaxis, readers are referred to the related EAACI Anaphylaxis Guidelines., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Recent studies on cashew nut allergy suggest that the prevalence of cashew nut allergy is increasing. Cashew nut consumption by allergic patients can cause severe reactions, including anaphylaxis. This review summarizes current knowledge on cashew nut allergy to facilitate timely clinical recognition and to promote awareness of this emerging food allergy amongst clinicians. The goal of this study is to present a systematic review focused on the clinical aspects of allergy to cashew nut including the characteristics of cashew nut, the prevalence, allergenic components, cross-reactivity, diagnosis and management of cashew nut allergy. The literature search yielded 255 articles of which 40 met our selection criteria and were considered to be relevant for this review. The 40 articles included one prospective study, six retrospective studies and seven case reports. The remaining 26 papers were not directly related to cashew nut allergy. The literature suggests that the prevalence of cashew nut allergy is increasing, although the level of evidence for this is low. A minimal amount of cashew nut allergen may cause a severe allergic reaction, suggesting high potency comparable with other tree nuts and peanuts. Cashew allergy is clearly an underestimated important healthcare problem, especially in children. [ABSTRACT FROM AUTHOR]

Background: Guideline-based treatment approaches for managing anaphylaxis are widely believed to result in good outcomes, but the strength of evidence underpinning the recommendations made therein is unclear., Objective: To identify and compare national guidelines for the emergency medical management of anaphylaxis and to describe the extent to which the evidence base in support of key recommendations is made clear., Methods: We systematically searched key medical databases and contacted the World Allergy Organization and anaphylaxis charities in several countries to identify national guidelines. Full text copies of relevant papers were obtained and, where necessary, translated. Data were abstracted onto a customized data extraction sheet; this process was independently checked by a second reviewer., Results: Guidelines originating from Australia, Canada, Russia, UK, Ukraine and the USA were identified. While these were in agreement on the broad principles of management, there were important variations in relation to the treatments to be used and the dose and route of administration of these preparations. Most guidelines failed to make clear the strength of evidence underpinning the recommendations being made., Conclusions: There are important international differences in the recommended emergency management of anaphylaxis. It is important that an agreed core evidence-based guideline for the management of anaphylaxis is now developed, which can then be adapted for national/local use. Clinicians need to be aware of the limitations of existing guidelines.

To cite this article: Cernadas JR, Brockow K, Romano A, Aberer W, Torres MJ, Bircher A, Campi P, Sanz ML, Castells M, Demoly P, Pichler WJ, for the European Network of Drug Allergy and the EAACI interest group on drug hypersensitivity. General considerations on rapid desensitization for drug hypersensitivity - a consensus statement. Allergy 2010; 65: 1357-1366. Drug hypersensitivity reactions can occur with most drugs, are unpredictable, may affect any organ or system, and range widely in clinical severity from mild pruritus to anaphylaxis. In most cases, the suspected drug is avoided in the future. However, for certain patients, the particular drug may be essential for optimal therapy. Under these circumstances, desensitization may be performed. Drug desensitization is defined as the induction of a temporary state of tolerance of a compound responsible for a hypersensitivity reaction. It is performed by administering increasing doses of the medication concerned over a short period of time (from several hours to a few days) until the total cumulative therapeutic dose is achieved and tolerated. It is a high-risk procedure used only in patients in whom alternatives are less effective or not available after a positive risk/benefit analysis. Desensitization protocols have been developed and are used in patients with allergic reactions to antibiotics (mainly penicillin), insulins, sulfonamides, chemotherapeutic and biologic agents, and many other drugs. Desensitization is mainly performed in IgE-mediated reactions, but also in reactions where drug-specific IgE have not been demonstrated. Desensitization induces a temporary tolerant state, which can only be maintained by continuous administration of the medication. Thus, for treatments like chemotherapy, which have an average interval of 4 weeks between cycles, the procedure must be repeated for every new course. In this paper, some background information on rapid desensitization procedures is provided. We define the drugs and drug reactions indicated for such procedures, describe the possible mechanism of action, and discuss the indications and contraindications. The data should serve as background information for a database (accessible via the EAACI-homepage) with standardized protocols for rapid desensitization for antibiotics, chemotherapeutic agents, monoclonal antibodies/fusion proteins, and other drugs. [ABSTRACT FROM AUTHOR]

Background: Having a better understanding of the risk factors of severe anaphylaxis is a crucial challenge for physicians. Methods: To retrospectively analyse fatal/near‐fatal anaphylaxis cases recorded by the Allergy‐Vigilance® Network (2002–2020) and evaluate the characteristics associated with survival, age and allergens. Results: Among the 3510 anaphylaxis cases documented in the network, 70 (2%) patients (males: 57%; mean age: 35.4 y) presented grade 4 (Ring‐Messmer) anaphylaxis and 25 died (19 food‐related); 33% had a history of asthma. The main allergens were food (60%; peanut, 20%; milks, 11%) involved in 25/26 cases in children and in 17/44 (39%) cases in adults. Non‐food anaphylaxis was related to drugs/latex (24%; neuromuscular blocking agents, 10%; betalactamins, 6%), Hymenoptera (16%). Three food‐related cases (one death) occurred during oral food challenge in children. Patients with a food allergy were younger (22.2 years vs. 55 years, p <.001), had more likely a history of asthma (50% vs. 7%; p <.001), a pre‐existing allergy (62% vs. 18%; p <.001) compared with other allergies. A cofactor was identified in 35 cases (50%) but predominantly in adults as opposed to children (64% vs. 27%; p =.01). The patients who died were younger (25.6 vs. 40.8 years; p =.01) than the survivors and mostly presented bronchospasm (56% vs. 29%; p =.05). Gaps in the prevention and management of anaphylaxis were noted in 15 cases (21%). Conclusions: Severe food anaphylaxis has specific features compared with other causes such as young age, asthma history and exercise. Food is also involved in severe anaphylaxis in adults that should not be underestimated. [ABSTRACT FROM AUTHOR]

Background: Alpha‐gal syndrome (AGS) is an IgE‐mediated allergy to galactose‐alpha‐1,3‐galactose. Clinical presentation ranges from hives to anaphylaxis; episodes typically occur 2–6 h after exposure to alpha‐gal‐containing products. In the United States, lone star tick bites are associated with the development of AGS. To characterize features of AGS, we evaluated a cohort of patients presenting for care at the University of North Carolina, focusing on symptoms, severity, and identifying features unique to specific alpha‐gal‐containing product exposures. Methods: We performed a chart review and descriptive analysis of 100 randomly selected patients with AGS during 2010–2019. Results: Median age at onset was 53 years, 56% were female, 95% reported White race, 86% reported a history of tick bite, and 75% met the criteria for anaphylaxis based on the involvement of ≥2 organ systems. Those reporting dairy reactions were significantly less likely to report isolated mucocutaneous symptoms (3% vs. 24%; ratio [95% CI]: 0.1 [0.1, 0.3]) than those who tolerated dairy, and were more likely to report gastrointestinal symptoms (79% vs. 59%; ratio [95% CI]: 1.3 [0.7, 2.6]), although this difference was not statistically significant. Dairy‐tolerant patients demonstrated higher alpha‐gal sIgE titers (as a percentage of total IgE) than dairy‐reactive patients (GM 4.1 [95% CI: 2.7, 6.1] vs. GM 2.5 [95% CI: 1.3, 4.8], respectively; ratio −1.6 [95% CI: −1.0, 3.9]). Conclusion: While tick exposure is common in the southern United States, nearly all AGS patients reported a tick bite. Gastrointestinal symptoms were prominent among those reporting reactions to dairy. Anaphylaxis was common, underscoring the severity and need to raise awareness of AGS among patients and providers. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of allergic reactions to penicillins (AR‐PEN) is very complex as there is a loss of sensitization over time, which leads to negative skin tests (STs) and specific IgE in serum, and even to tolerance to the drug involved. However, STs may become positive after subsequent exposure to the culprit drug (resensitization), with the risk of inducing potentially severe reactions. The exact rate of resensitization to penicillins is unknown, ranging from 0% to 27.9% in published studies. Objectives: To analyze the rate of resensitization in patients with suggestive AR‐PEN by repeating STs (retest) after an initial evaluation (IE). Material and Methods: Patients with suspected AR‐PEN were prospectively evaluated between 2017 and 2020. They underwent STs, and a randomized group also underwent a drug provocation test (DPT) with the culprit. Only patients with negative STs and/or DPT were included. All included cases were retested by STs at 2–8 weeks. Results: A total of 545 patients were included: 296 reporting immediate reactions (IRs) and 249 non‐immediate reactions (NIRs). Eighty (14.7%) cases had positive results in retest (RT+): 63 (21.3%) IRs and 17 (6.8%) NIRs (p < 0.0001). The rate of RT+ was higher in anaphylaxis compared with all other reactions (45.8% vs 9.1%, p < 0.0001). The risk of RT+ was higher from the fifth week after IE (OR: 4.64, CI: 2.1–11.6; p < 0.001) and increased with the patient's age (OR: 1.02; CI: 1.01–1.04; p = 0.009). Conclusions: Due to the high rate of resensitization, retest should be included in the diagnostic algorithm of IRs to penicillins after an initial negative study, especially in anaphylaxis, to avoid potentially severe reactions after subsequent prescriptions of these drugs. [ABSTRACT FROM AUTHOR]

Background: Anaphylaxis is the most acute and life‐threatening manifestation of allergic disorders. Currently, there is a need to improve its medical management and increase the understanding of its molecular mechanisms. This study aimed to quantify the extravasation underlying human anaphylactic reactions and propose new theragnostic approaches. Methods: Molecular determinations were performed in paired serum samples obtained during the acute phase and at baseline from patients presenting with hypersensitivity reactions. These were classified according to their severity as Grades 1, 2 and 3, the two latter being considered anaphylaxis. Tryptase levels were measured by ImmunoCAP, and serum protein concentration was quantified by Bradford assay. Human serum albumin (HSA) and haemoglobin beta subunit (HBB) levels were determined by Western blot and polyacrylamide gel electrophoresis, respectively. Results: A total of 150 patients were included in the study. Of them, 112 had experienced anaphylaxis (83 and 29 with Grade 2 and 3 reactions, respectively). Tryptase diagnostic efficiency substantially improved when considering patients' baseline values (33%–54%) instead of the acute value threshold (21%). Serum protein concentration and HSA significantly decreased in anaphylaxis (p <.0001). HSA levels dropped with the severity of the reaction (6% and 15% for Grade 2 and 3 reactions, respectively). Furthermore, HBB levels increased during the acute phase of all hypersensitivity reactions (p <.0001). Conclusions: For the first time, the extravasation underlying human anaphylaxis has been evaluated based on the severity of the reaction using HSA and protein concentration measurements. Additionally, our findings propose new diagnostic and potential therapeutic approaches for this pathological event. [ABSTRACT FROM AUTHOR]