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Drug reactions are common and have a major impact on prescribing behaviour in the Netherlands. An adequate allergy registration is essential both to avoid re-exposition and to prevent unnecessary avoidance. An incomplete or incorrect registration of allergies is a threat to good medical practice, unnecessarily leading to sub-optimal treatment. National registries such as the Dutch 'LandelijkSchakelpunt' (LSP), must be easily accessible to all care providers and kept up-to-date. Healthcare providers should be properly trained in recognizing allergies as well as correct allergy registration. Additionally, healthcare providers must be given the opportunity to register as well as delete allergies from registry systems.

The Core Outcome Set for Therapeutic Studies in Eosinophilic Esophagitis (COREOS) collaborators are a group of more than 70 gastroenterologists, pathologists, allergists, researchers, dietitians, psychologists, and methodologists who convened in a series of in-person and virtual meetings between 2018 and 2020 with the aim of developing a core outcome set (COS) for use in therapeutic studies of pharmacologic and dietary therapies for the treatment of eosinophilic esophagitis (EoE). Given heterogeneity in reported outcomes and uncertainties regarding the most appropriate end points for use in both randomized controlled trials (RCTs) and observational studies involving EoE patients, the EoE experts launched the COREOS exercise in 2018 to standardize outcome definitions using methods established by the Core Outcome Measures in Effectiveness Trials (COMET) initiative.1,2 The COS was developed using a multiphase approach, which is summarized in Figure 1. In the first phase, systematic reviews of the literature and patient engagement surveys were conducted to identify candidate outcomes that have been previously measured and are important to patients with EoE. Next, this information was used to build a framework of different outcome domains, and working groups for each domain were assembled to review the literature for relevant end points.3–6 The relative importance of these domains was categorized in a Delphi survey as core, important, and research agenda domains, and discussed in a moderated in-person meeting on May 17, 2019 at Digestive Disease Week (San Diego, CA). In phase 3, a comprehensive list of outcome measures within each of the core domains was evaluated by the COREOS collaborators in a 2-round Delphi survey and, finally, outcomes were ratified in a virtual meeting on December 8, 2020. In this meeting summary, we highlight the major points of discussion that occurred during the development of the EoE COS.

Perioperative allergic reactions are rare, yet important complications of anesthesia. Severe, generalized allergic reactions called anaphylaxis are estimated to have a mortality of 3.5–4.8%. Adequate recognition and handling of a severe perioperative anaphylactic reaction result in better outcomes, including less hypoxic-ischemic encephalopathy and death. The diagnosis of a perioperative allergic reaction can be difficult as the list of possible culprits of a perioperative allergic reaction is extensive. Making an informed guess on the causative agent and avoiding this agent in future anesthesia procedures is undesirable and unsafe. Therefore, to ensure future patient safety, a thorough investigation following a perioperative allergic reaction is mandatory. A collaborate approach by allergists and anesthesiologists is advised. In this article, we discuss the basic approach of the allergic patient and of patients with a suspected allergy to perioperatively administered medication.

Purpose: Eosinophilic esophagitis (EoE) is a chronic immune-mediated esophageal disease. Most EoE patients have atopic comorbidities and they test positive when allergy tests are performed. Our aim is to critically assess the relation of allergens detected by allergy tests with clinically confirmed triggers of EoE. Methods: A systemic review and meta-analysis will be conducted, which will involve searching electronic databases using predetermined search terms, in order to identify relevant studies. Studies will be independently screened against predefined eligibility criteria and subgroup analysis will be used for the outcomes. Results and conclusion: The findings of this review are going to help clinicians and allied health professionals in treatment decisions.

BACKGROUND: End points used to determine treatment efficacy in eosinophilic esophagitis (EoE) have evolved over time. With multiple novel therapies in development for EoE, harmonization of outcomes measures will facilitate evidence synthesis and appraisal when comparing different treatments. OBJECTIVE: We sought to develop a core outcome set (COS) for controlled and observational studies of pharmacologic and diet interventions in adult and pediatric patients with EoE. METHODS: Candidate outcomes were generated from systematic literature reviews and patient engagement interviews and surveys. Consensus was established using an iterative Delphi process, with items voted on using a 9-point Likert scale and with feedback from other participants to allow score refinement. Consensus meetings were held to ratify the outcome domains of importance and the core outcome measures. Stakeholders were recruited internationally and included adult and pediatric gastroenterologists, allergists, dieticians, pathologists, psychologists, researchers, and methodologists. RESULTS: The COS consists of 4 outcome domains for controlled and observational studies: histopathology, endoscopy, patient-reported symptoms, and EoE-specific quality of life. A total of 69 stakeholders (response rate 95.8%) prioritized 42 outcomes in a 2-round Delphi process, and the final ratification meeting generated consensus on 33 outcome measures. These included measurement of the peak eosinophil count, Eosinophilic Esophagitis Histology Scoring System, Eosinophilic Esophagitis Endoscopic Reference Score, and patient-reported measures of dysphagia and quality of life. CONCLUSIONS: This interdisciplinary collaboration involving global stakeholders has produced a COS that can be applied to adult and pediatric studies of pharmacologic and diet therapies for EoE and will facilitate meaningful treatment comparisons and improve the quality of data synthesis. ispartof: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY vol:149 issue:2 pages:659-670 ispartof: location:United States status: published

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.

International audience; Drug hypersensitivity reactions (DHRs) are associated with high global morbidity and mortality. Cutaneous T cell-mediated reactions classically occur more than 6 hours after drug administration and include life-threatening conditions such as toxic epidermal necrolysis, Stevens-Johnson syndrome, and hypersensitivity syndrome. Over the last 20 years, significant advances have been made in our understanding of the pathogenesis of DHRs with the identification of human leukocyte antigens as predisposing factors. This has led to the development of pharmacogenetic screening tests, such as HLA-B*57:01 in abacavir therapy, which has successfully reduced the incidence of abacavir hypersensitivity reactions. We have completed a PRISMA-compliant systematic review to identify genetic associations that have been reported in DHRs. In total, 105 studies (5554 cases and 123 548 controls) have been included in the review reporting genetic associations with carbamazepine (n = 31), other aromatic antiepileptic drugs (n = 24), abacavir (n = 11), nevirapine (n = 14), trimethoprim-sulfamethoxazole (n = 11), dapsone (n = 4), allopurinol (n = 10), and other drugs (n = 5). The most commonly reported genetic variants associated with DHRs are located in human leukocyte antigen genes and genes involved in drug metabolism pathways. Increasing our understanding of genetic variants that contribute to DHRs will allow us to improve diagnosis, develop new treatments, and predict and prevent DHRs in the future.

A β-LACTAM allergy is the most common suspected inhospital drug allergy, with an incidence of 5 to 17% in hospitalized patients and up to 35% in the surgical population at the preoperative assessment clinic.1-5 Thus, the team in the operating theater will be confronted with these patients when perioperative antibiotic prophylaxis is needed. Frequently, the consequence of a presumed β-lactam allergy is that all β-lactam antibiotics are avoided, because of the possibility of cross-reactivity, and an alternative antibiotic, e.g., clindamycin, vancomycin, or ciprofloxacin, is prescribed.1 This may be a short-term risk-avoiding strategy during surgery, but the long-term consequences are overuse of these agents and an increase in serious hospital infections by pathogens such as Clostridium difficile and vancomycin-resistant Enterococcus, with an accompanied rise in healthcare use and costs.4 In fact, the overuse of non-β-lactam antibiotics because of reported penicillin allergy has been labeled a public health problem.6-8 In this review, we provide an evidencebased and practical approach to patients with presumed β-lactam allergy admitted to the operating theater and give guidance on the selection of alternative antibiotics based on cross-reactivity patterns.

Immunization is highly effective in preventing infectious diseases and therefore an indispensable public health measure. Allergic patients deserve access to the same publicly recommended immunizations as nonallergic patients unless risks associated with vaccination outweigh the gains. Whereas the number of reported possible allergic reactions to vaccines is high, confirmed vaccine-triggered allergic reactions are rare. Anaphylaxis following vaccination is rare, affecting less than 1/100,000, but can occur in any patient. Some patient groups, notably those with a previous allergic reaction to a vaccine or its components, are at heightened risk of allergic reaction and require special precautions. Allergic reactions, however, may occur in patients without known risk factors and cannot be predicted by currently available tools. Unwarranted fear and uncertainty can result in incomplete vaccination coverage for children and adults with or without allergy. In addition to concerns about an allergic reaction to the vaccine itself, there is fear that routine childhood immunization may promote the development of allergic sensitization and disease. Thus, although there is no evidence that routine childhood immunization increases the risk of allergy development, such risks need to be discussed. This article is protected by copyright. All rights reserved.

Eosinophilic esophagitis (EoE) is one of the most prevalent esophageal diseases and the leading cause of dysphagia and food impaction in children and young adults. This underlines the importance of optimizing diagnosys and treatment of the condition, especially after the increasing amount of knowledge on EoE recently published. Therefore, the UEG, EAACI ESPGHAN, and EUREOS deemed it necessary to update the current guidelines regarding conceptual and epidemiological aspects, diagnosis, and treatment of EoE. General methodology according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used in order to comply with current standards of evidence assessment in formulation of recommendations. An extensive literature search was conducted up to August 2015 and periodically updated. The working group consisted of gastroenterologists, allergists, pediatricians, otolaryngologists, pathologists, and epidemiologists. Systematic evidence-based reviews were performed based upon relevant clinical questions with respect to patient-important outcomes. The guidelines include updated concept of EoE, evaluated information on disease epidemiology, risk factors, associated conditions, and natural history of EoE in children and adults. Diagnostic conditions and criteria, the yield of diagnostic and disease monitoring procedures, and evidence-based statements and recommendation on the utility of the several treatment options for patients EoE are provided. Recommendations on how to choose and implement treatment and long-term management are provided based on expert opinion and best clinical practice. Evidence-based recommendations for EoE diagnosis, treatment modalities, and patients' follow up are proposed in the guideline

Drug hypersensitivity reactions (DHR) constitute a major and common public health problem, particularly in children. One of the most severe manifestations of DHR is anaphylaxis, which might be associated with a life-threatening risk. During those past decades, anaphylaxis has received particularly a lot of attention and international consensus guidelines have been recently published. Whilst drug-induced anaphylaxis is more commonly reported in adulthood, less is known about the role of drugs in pediatric anaphylaxis. Betalactam antibiotics and non-steroidal anti-inflammatory drugs are the most commonly involved drugs, probably related to high prescription rates. Diagnosis relies on the recognition of symptoms pattern and is based on complete allergic workup, particularly including skin tests and/or specific IgE. However, the real diagnostic value of those tests to diagnose immediate reactions in children remains not well defined for a significant number of the drugs. Generally, a drug provocation test is discussed to confirm or exclude an immediate-onset drug-induced hypersensitivity. Although avoidance of the incriminated drug (and related drug) is the rule, rapid desensitization is useful in selected subgroups of patients. There is a need for large, multicentric studies, to evaluate the real diagnostic value of the currently available skin tests. Moreover there is also a need to develop new diagnostic tests in the future to improve the management of these children.

The strongest and best-documented risk factor for drug hypersensitivity (DH) is the history of a previous reaction. Accidental exposures to drugs may lead to severe or even fatal reactions in sensitized patients. Preventable prescription errors are common. They are often due to inadequate medical history or poor risk assessment of recurrence of drug reaction. Proper documentation is essential information for the doctor to make sound therapeutic decision. The European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology have formed a task force and developed a drug allergy passport as well as general guidelines of drug allergy documentation. A drug allergy passport, a drug allergy alert card, a certificate, and a discharge letter after medical evaluation are adequate means to document DH in a patient. They are to be handed to the patient who is advised to carry the documentation at all times especially when away from home. A drug allergy passport should at least contain information on the culprit drug(s) including international nonproprietary name, clinical manifestations including severity, diagnostic measures, potential cross-reactivity, alternative drugs to prescribe, and where more detailed information can be obtained from the issuer. It should be given to patients only after full allergy workup. In the future, electronic prescription systems with alert functions will become more common and should include the same information as in paper-based documentation.

International audience; Drug hypersensitivity includes allergic (AR) and nonallergic reactions (NARs) influenced by genetic predisposition. We performed a systematic review of genetic predictors of IgE-mediated AR and NAR with MEDLINE and PubMed search engine between January 1966 and December 2014. Among 3110 citations, the search selected 53 studies, 42 of which remained eligible. These eligible studies have evaluated genetic determinants of immediate reactions (IR) to beta-lactams (n = 19), NAR against aspirin (n = 12) and other nonsteroidal anti-inflammatory drugs (NSAIDs) (n = 8), and IR to biologics (n = 3). We reported two genomewide association studies and four case–control studies on candidate genes validated by replication. Genes involved in IR to beta-lactams belonged to HLA type 2 antigen processing, IgE production, atopy, and inflammation, including 4 genes validated by replications, HLA-DRA, ILR4, NOD2, and LGALS3. Genes involved in NAR to aspirin belonged to arachidonic acid pathway, membrane-spanning 4A gene family, histamine production pathway, and pro-inflammatory cytokines, while those involved in NAR to all NSAIDs belonged to arachidonic acid pathway and HLA antigen processing pathway. ALOX5 was a common predictor of studies on NAR to both aspirin and NSAIDs. Although these first conclusions could be drawn, this review highlights also the lack of reliable data and the need for replicating studies in contrasted populations, taking into account worldwide allele frequencies, gene–gene interactions, and contrasted situations of environmental exposure.

Background Endotyping chronic rhinitis has proven hardest for the subgroup of non-allergic rhinitis (NAR) patients. While IgE-related inflammation is typical for allergic rhinitis (AR), no markers have been found that can be seen to positively identify NAR. A further complication is that AR and NAR might co-exist in patients with mixed rhinitis. As previous studies have considered only a limited number of inflammatory mediators, we wanted to explore whether a wider panel of mediators could help us refine the endotyping in chronic rhinitis patients. Objective To endotype chronic rhinitis, and non-allergic rhinitis in particular, with help of molecular or cellular markers. Method In this study we included 23 NAR patients without allergen sensitizations and with persistent rhinitis symptoms, 22 pollen sensitized rhinitis patients with seasonal symptoms, 21 mixed rhinitis patients with pollen-related symptoms and persistent symptoms outside of the pollen season, and 23 healthy controls without any symptoms. Nasal secretions were collected outside of pollen season and differences between the endotypes were assessed for a broad range of inflammatory mediators and growths factors using a multiplex ELISA. Results Although we were able to identify two new nasal secretion makers (IL-12 and HGF) that were low in mixed and AR patients versus NAR and healthy controls, the most intriguing outcome is that despite investigating 29 general inflammatory mediators and growth factors no clear profile of non-allergic or mixed rhinitis could be found. Conclusion Classical inflammatory markers are not able to differentiate between non-allergic or mixed rhinitis patients and healthy controls.

Adverse drug reactions include drug hypersensitivity reactions (DHRs), which can be immunologically mediated (allergy) or non-immunologically mediated. The high number of DHRs that are unconfirmed and often self-reported is a frequent problem in daily clinical practice, with considerable impact on future prescription choices and patient health. It is important to distinguish between hypersensitivity and non-hypersensitivity reactions by adopting a structured diagnostic approach to confirm or discard the suspected drug, not only to avoid life-threatening reactions, but also to reduce the frequent over-diagnosis of DHRs. Primary care physicians are often the first point of contact for the sufferer of a reaction, as such they have a key role in deciding whether to discard the diagnosis or send the patient for further investigation. In this review, we highlight the importance of diagnosing DHRs, analysing in detail the role of primary care physicians. We describe the common patterns of DHRs and signs of its progression, as well as the indications and contraindications for referring the patient to an allergist. The diagnostic process is described and the possible tests are discussed, which often depend on the drug involved and the type of DHR suspected. We also describe recommendations regarding the avoidance of medication suspected to have caused the reaction and the use of alternatives.

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in the pediatric population as antipyretics/analgesics and anti-inflammatory medications. Hypersensitivity (HS) reactions to NSAID in this age group, while similar to adults, have unique diagnostic and management issues. Although slowly accumulating, published data in this age group are still relatively rare and lacking a unifying consensus. This work is a summary of current knowledge and consensus recommendations utilizing both published data and expert opinion from the European Network of Drug Allergy (ENDA) and the Drug Hypersensitivity interest group in the European Academy of Allergy and Clinical Immunology (EAACI). This position paper summarizes diagnostic and management guidelines for children and adolescents with NSAIDs hypersensitivity.

In contrast to the well-known significant impairment of quality of life (QoL) in allergic rhinitis (AR), the degree of impairment in QoL in non-allergic rhinitis (NAR) remained unknown for a long time, due to a lack of a validated questionnaire to assess QoL in the NAR patient group. In this study a validation for the mini-RQLQ questionnaire in NAR patients was performed, followed by an assessment of QoL in NAR patients compared to AR and healthy controls. Secondly, use of medication and treatment satisfaction in AR and NAR was assessed. The study was an observational cohort study in 287 AR and 160 NAR patients. Patients with symptoms of rhinitis were recruited from a tertiary care outpatient clinic of the Otorhinolaryngology Department. AR was defined as one or more positive results on skin prick testing and clinically relevant symptoms of rhinitis related to their sensitization. NAR was defined as clinically relevant symptoms of rhinitis but without positive results on skin prick testing. The mini-RQLQ was successfully validated in this study for NAR patients. QoL in NAR patients was equally -and for some aspects even more- impaired compared to AR. More than half of both AR and NAR patients were unsatisfied with treatment. These results demonstrate a significant impairment in both AR and NAR patients in their QoL combined with a low treatment satisfaction, emphasizing the need for adequate treatment, especially in the NAR patient group. This article is protected by copyright. All rights reserved

Eosinophilic esophagitis (EoE) has repeatedly been associated with atopic manifestations, which are reported more frequently in these patients than in the general population.To systematically assess the evidence and strength of the associations between EoE and atopy.We performed a systematic search of the MEDLINE, EMBASE, and SCOPUS databases for case-control studies comparing the frequency of atopic diatheses among patients with EoE and control subjects representing the general population without EoE. Using random-effects meta-analyses, we calculated summary estimates, including 95% confidence intervals (CIs), for bronchial asthma, atopic rhinitis, and eczema. Publication bias risks were assessed by means of funnel plot analysis and specific statistical tests.Of the 2,954 references identified, data were collected from 21 studies, including a total of 53,542 patients with EoE and 54,759 controls. The criteria for defining a diagnosis of atopy in patients with EoE or controls was not structurally considered in most of the studies. Overall, allergic rhinitis was significantly more common among patients with EoE compared with control subjects (odds ratio [OR], 5.09; 95% CI, 2.91-8.90; IDespite pointing to a significant association between atopy and EoE, most of the studies provided no normalized diagnostic criteria for atopy. Further research should provide clear and standardized definitions of such conditions.www.crd.york.ac.uk/PROSPERO Trial Identifier: CRD42016036161.

Drug allergy pathways are standardized approaches for patients reporting prior drug allergies with the aim of quality improvement and promotion of antibiotic stewardship. At the International Drug Allergy Symposium during the 2018 American Academy of Allergy, Asthma, and Immunology/World Allergy Organization Joint Congress in Orlando, Florida, drug allergy pathways were discussed from international perspectives with a focus on beta-lactam allergy pathways and pragmatic approaches for acute care hospitals. In this expert consensus document, we review current pathways, and detail important considerations in devising, implementing, and evaluating beta-lactam allergy pathways for hospitalized patients. We describe the key patient and institutional factors that must be considered in risk stratification, the central feature of pathway design. We detail shared obstacles to widespread beta-lactam allergy pathway implementation and identify potential solutions to address these challenges.

Research in rhinitis has primarily focused on allergic rhinitis and important aspects of the disease such as the IgE-mediated inflammatory cascade, the impact on quality of life, the impact on the lower airways, and control and severity of the disease, especially in those patients in which control is not easily obtained. However, a significant number of patients with persistent rhinitis do not show systemic sensitization to aeroallergens or signs of infection. These patients are defined under the umbrella term “nonallergic rhinitis” or “noninfectious rhinitis.” Nonallergic rhinitis comprises a large number of phenotypes and endotypes, such as rhinitis medicamentosa, drug-induced rhinitis, rhinitis of the elderly, idiopathic rhinitis, and local allergic rhinitis. This review describes the new pathophysiology and clinical insights into these different forms of nonallergic rhinitis with special emphasis on local allergy. New recommendations in diagnosis and treatment are given.

Aim: Angioedema and cough are the two most important adverse effects of ACE inhibitors (ACEIs). Evidence exists that ACEI-related angioedema/cough is partly genetically determined and several genes have been identified to play a role in the development of ACEI-related adverse effects. Materials & methods: This study was performed in order to evaluate the evidence of these genetic associations and ACEIs’ adverse effects. After removing duplicates and critical appraisal, 19 studies were considered to be eligible to review; 14 articles about cough and five articles about angioedema. A separate meta-analysis was performed for the most studied ACE insertion/deletion polymorphism (rs4646994) and its association with cough. Results & conclusion: One gene region (XPNPEP2) was associated with ACEI-induced angioedema in three studies. In our meta-analysis we did not find a significant association between the ACE insertion/deletion polymorphism and ACEI cough. Original submitted 27 September 2012; Revision submitted 6 December 2012

Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow-up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria and atopic dermatitis) in order to have a uniform definition of severity, control and risk, usable in most situations. It is based on the appropriate diagnosis, availability and accessibility of treatments, treatment responsiveness and associated factors such as comorbidities and risk factors. This uniform definition will allow a better definition of the phenotypes of severe allergic (and related) diseases for clinical practice, research (including epidemiology), public health purposes, education and the discovery of novel therapies.

Adverse drug reactions (ADR) can result from immune-mediated (drug allergy) and nonimmune-mediated mechanisms. In both types of reaction, conclusive diagnosis and appropriate management remain major problems in daily clinical practice. This review summarizes the potentials and shortcomings of the currently available in vitro tests in the diagnosis of immediate (mostly IgE mediated) and nonimmediate (mostly T-cell mediated) drug allergy, particularly quantification of specific IgE, flow-assisted analysis of in vitro activated lymphocytes and basophils and the enzyme-linked immunosorbent spot.

To cite this article: Baiardini I, Braido F, Bindslev-Jensen C, Bousquet PJ, Brzoza Z, Canonica GW, Compalati E, Fiocchi A, Fokkens W, Gerth van Wijk R, Gimenez-Arnau A, Godse K, Grattan C, Grob JJ, La Grutta S, Kalogeromitros D, Kocaturk E, Lombardi C, Mota-Pinto A, Ridolo E, Saini SS, Sanchez-Borges M, Senna GE, Terreehorst I, Todo Bom A, Toubi E, Bousquet J, Zuberbier T, Maurer M. Recommendations for assessing patient-reported outcomes and health-related quality of life in patients with urticaria: a GA2LEN taskforce position paper. Allergy 2011; 66: 840–844. Abstract The aim of this Global Allergy and Asthma European Network (GA2LEN) consensus report is to provide recommendations and suggestions for assessing patient-reported outcomes (PROs) including health-related quality of life in patients with urticaria. We recommend that PROs should be used both in clinical trials and routine practice for the evaluation of urticaria patients. We suggest that PROs should be considered as the primary outcome of future clinical trials. Two validated and disease-specific instruments for assessing PROs are available, the urticaria activity score (for symptoms) and the chronic urticaria questionnaire on quality of life CU-Q2oL. This latter tool, CU-Q2oL, is available in many languages and should be preferred, where available, over more generic instruments for assessing urticaria-specific effects on quality of life. CU-Q2oL is only suited for the investigation of patients with chronic spontaneous urticaria. Similar instruments for other forms of urticaria have yet to be developed and validated. Also, tools for assessing other chronic spontaneous urticaria PROs besides quality of life and symptoms are needed.

The GA 2 LEN taskforce on Patient-Reported Outcomes (PROs) and Health-Related Quality of Life (HRQoL) published in 2009 a position paper concerning PROS and HRQoL assessment in clinical trials on allergy. Because of the specificity of this topic in asthma and rhinitis, specific recommendations are needed. The aim of this position paper is to define PROs and their meaning in asthma and rhinitis research, explore the available tools to provide criteria for a proper choice, identify patientrelated factor which could influence PROs assessment, define specific recommendations for assessment, analysis and results spreading, underline the unexplored areas and unmet needs. PROs assessment is gaining increasing importance, and it must be performed with a rigorous methodological procedure and using validated tools. This approach enables to better understand patient-related factors influencing clinical trials and real-life management outcomes, identify patients subgroups that can benefit from specific treatment and management plan and tailor treatment to address PROs (not only physician-defined targets) to improve asthma and rhinitis management.

Nonallergic hypersensitivity and allergic reactions are part of the many different types of adverse drug reactions (ADRs). Databases exist for the collection of ADRs. Spontaneous reporting makes up the core data-generating system of pharmacovigilance, but there is a large under-estimation of allergy/hypersensitivity drug reactions. A specific database is therefore required for drug allergy and hypersensitivity using standard operating procedures (SOPs), as the diagnosis of drug allergy/hypersensitivity is difficult and current pharmacovigilance algorithms are insufficient. Although difficult, the diagnosis of drug allergy/hypersensitivity has been standardized by the European Network for Drug Allergy (ENDA) under the aegis of the European Academy of Allergology and Clinical Immunology and SOPs have been published. Based on ENDA and Global Allergy and Asthma European Network (GA(2)LEN, EU Framework Programme 6) SOPs, a Drug Allergy and Hypersensitivity Database (DAHD((R))) has been established under FileMaker((R)) Pro 9. It is already available online in many different languages and can be accessed using a personal login. GA(2)LEN is a European network of 27 partners (16 countries) and 59 collaborating centres (26 countries), which can coordinate and implement the DAHD across Europe. The GA(2)LEN-ENDA-DAHD platform interacting with a pharmacovigilance network appears to be of great interest for the reporting of allergy/hypersensitivity ADRs in conjunction with other pharmacovigilance instruments.

Eozynofilowe zapalenie przełyku (eosinophilic esophagitis − EoE) jest najczęstszą chorobą przełyku, prowadzącą do dysfagii i zaburzeń odżywiania u dzieci i młodych dorosłych. W związku z tym oraz z uwagi na znaczną liczbę opublikowanych w ostatnim czasie badań na temat EoE bardzo istotna jest optymalizacja rozpoznania i leczenia. Towarzystwa UEG, EAACI, ESPGHAN i EUREOS uznały za konieczne zaktualizowanie wytycznych w zakresie etiologii, epidemiologii, diagnostyki i terapii EoE. Metody. Zastosowano metodologię zgodną z AGREE II (Appraisal of Guidelines for Research and Evaluation) i GRADE (Grading of Recommendations Assessment, Development, and Evaluation), czyli aktualnymi standardami oceny dowodów w formułowaniu rekomendacji.Wyniki. Wytyczne zawierają uaktualnione dane na temat etiologii EoE, epidemiologii, czynników ryzyka, chorób towarzyszących i historii naturalnej EoE u dzieci i dorosłych. Dostarczają informacji o badaniach diagnostycznych i kryteriach rozpoznania, procedurach monitorowania oraz prezentują oparte na faktach zalecenia i rekomendacje dotyczące różnych metod leczenia.Wnioski. W wytycznych zaproponowano oparte na faktach rekomendacje dotyczące rozpoznawania, leczenia i nadzoru pacjentów z EoE.

Background Eosinophilic esophagitis (EoE) has repeatedly been associated with atopic manifestations, which are reported more frequently in these patients than in the general population. Objective To systematically assess the evidence and strength of the associations between EoE and atopy. Methods We performed a systematic search of the MEDLINE, EMBASE, and SCOPUS databases for case-control studies comparing the frequency of atopic diatheses among patients with EoE and control subjects representing the general population without EoE. Using random-effects meta-analyses, we calculated summary estimates, including 95% confidence intervals (CIs), for bronchial asthma, atopic rhinitis, and eczema. Publication bias risks were assessed by means of funnel plot analysis and specific statistical tests. Results Of the 2,954 references identified, data were collected from 21 studies, including a total of 53,542 patients with EoE and 54,759 controls. The criteria for defining a diagnosis of atopy in patients with EoE or controls was not structurally considered in most of the studies. Overall, allergic rhinitis was significantly more common among patients with EoE compared with control subjects (odds ratio [OR], 5.09; 95% CI, 2.91–8.90; I 2 = 86.7%) as were bronchial asthma (OR, 3.01; 95% CI, 1.96–4.62; I 2 = 84.5%) and eczema (OR, 2.85; 95% CI, 1.87–4.34; I 2 = 57.1%). Food allergies and other atopic conditions were also assessed. No significant publication bias was found for studies dealing with allergic rhinitis and eczema in EoE. Conclusion Despite pointing to a significant association between atopy and EoE, most of the studies provided no normalized diagnostic criteria for atopy. Further research should provide clear and standardized definitions of such conditions. Trial Registration www.crd.york.ac.uk/PROSPERO Trial Identifier: CRD42016036161.

In contrast to hypersensitivity reactions (HSRs) to -lactam antibiotics in children, studies about HSR to non--lactam antibiotics (NBLAs) such as sulfonamides, macrolides, quinolones, and antituberculosis agents are scarce, and information is generally limited to case reports. The aim of this extensive review was to summarize our present knowledge on clinical characteristics, evaluation, and management of HSR to NBLAs in children based on the literature published between 1980 and 2013. NBLAs have been reported to induce a wide spectrum of HSRs from mild eruptions to severe, and sometimes fatal, systemic drug reactions, especially in some high-risk groups. The diagnosis relied upon history and remained unconfirmed by allergological tests in most of the cases. Obtaining a detailed history is valuable in the diagnosis of suspected reactions to NBLAs. Diagnostic in vivo and in vitro tests for NBLAs lack validation, which makes the diagnosis challenging. The definitive diagnosis of NBLA hypersensitivity frequently depends upon drug provocation tests. Studies including children showed that only 7.8 to 36% of suspected immediate and delayed HSRs to NBLAs could be confirmed by skin and/or provocation tests. Therefore, a standardized diagnostic approach and management strategy should be developed and employed for pediatric patients in the evaluation of suspected HSRs to NBLAs, some of which may be critical and unreplaceable in certain clinical situations. image

Skin tests are of paramount importance for the evaluation of drug hypersensitivity reactions. Drug skin tests are often not carried out because of lack of concise information on specific test concentrations. The diagnosis of drug allergy is often based on history alone, which is an unreliable indicator of true hypersensitivity.To promote and standardize reproducible skin testing with safe and nonirritant drug concentrations in the clinical practice, the European Network and European Academy of Allergy and Clinical Immunology (EAACI) Interest Group on Drug Allergy has performed a literature search on skin test drug concentration in MEDLINE and EMBASE, reviewed and evaluated the literature in five languages using the GRADE system for quality of evidence and strength of recommendation. Where the literature is poor, we have taken into consideration the collective experience of the group.We recommend drug concentration for skin testing aiming to achieve a specificity of at least 95%. It has been possible to recommend specific drug concentration for betalactam antibiotics, perioperative drugs, heparins, platinum salts and radiocontrast media. For many other drugs, there is insufficient evidence to recommend appropriate drug concentration. There is urgent need for multicentre studies designed to establish and validate drug skin test concentration using standard protocols. For most drugs, sensitivity of skin testing is higher in immediate hypersensitivity compared to nonimmediate hypersensitivity.

Angioedema is a potentially life-threatening adverse reaction to angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. To study the genetic etiology of this rare adverse event, international consortia and multicenter recruitment of patients are needed. To reduce patient heterogeneity, we have standardized the phenotype. In brief, it comprises swelling in the head and neck region that first occurs during treatment. It should not coincide with urticaria or have another likely cause such as hereditary angioedema.

Similarly to other medications, vaccines may be responsible for allergic reactions. Although IgE-mediated allergies to vaccine are extremely rare, they are clearly overdiagnosed. Indeed, accurate diagnosis of vaccine allergy is important not only to prevent serious or even life-threatening reactions, but also to avoid unnecessary vaccine restriction. Systematic approaches have been proposed and, if implemented, will likely reduce the number of children being inappropriately labeled as allergic to vaccine. In diagnosis of vaccine allergy, the patient's history is central although not sufficient. In case of suspicion of an allergy, the child should be referred to an allergist in order to perform a complete allergy workup, based primarily on skin tests and/or specific IgE. Highlighting the most recent literature, this article will address the management of children with a possible allergy to vaccine.

In a recent placebo-controlled study we demonstrated that capsaicin is an efficacious substance in the treatment of non-allergic non-infectious rhinitis. In this study the therapeutic effect lasted more than 9 months. This effect was not based on modulation of inflammation. To evaluate the effect of repeated application of capsaicin to patients with a nasal allergy to house dust mites (HDM), using the same treatment protocol as recently introduced in the treatment of non-allergic patients. Twenty-six patients with rhinitis, 15 females and 11 males (range: 20–46 years; mean 30.5), allergic to HDM were treated with either capsaicin or placebo in a double-blind, placebo-controlled, parallel group design. Nasal reactivity to HDM expressed as nasal symptoms, albumin and leukotriene levels in nasal lavage fluid and responsiveness to histamine, assessed as symptoms before and 6 weeks after treatment, were used to compare both treatment groups. In addition, visual analogue scales and rhinitis quality of life (RQL) assessment before, 6 weeks after and 3 months after treatment were used as outcome variables. No significant effect of capsaicin on nasal challenge tests with HDM (nasal symptoms, albumin and leukotriene levels), on VAS or RQL outcome 6 weeks or 3 month's after treatment, was demonstrated. Capsaicin did have a small effect on the area of the curve (AUC) of histamine dose response curves (P = 0.03). Desensitization with capsaicin in doses sufficient to control symptoms in patients with severe non-allergic rhinitis is lacking therapeutic effect in perennial allergic rhinitis.

EoE patients show variable sensitization patterns to food and aeroallergens. The value of allergy testing in adult EoE patients is unclear. Component-resolved diagnosis (CRD) may offer additional insights into sensitization patterns. The aim of this study was to characterize sensitization patterns in adult EoE patients using CRD. Serum from 76 patients (17 female), age 38.6 ± 1.5 years, was analyzed for reactivity to 112 different allergen components using an immuno-solid-phase allergen chip (ISAC). We observed any sensitization in 59 patients (78%), of which 54 patients were polysensitized. Aeroallergen sensitization, mostly against components of grass or tree pollen, or house dust mite, was observed in 74% of the patients. Birch pollen (rBet v 1) sensitization with cross-reactivity to food allergen components was observed in 30 patients (39%). In conclusion, food sensitizations in EoE patients are mainly caused by cross-reactivity to food allergens after primary birch pollen sensitization. Pollen and food sensitizations may cause or maintain esophageal inflammation in EoE patients. CRD provides more insight into sensitization patterns, identifies additional food allergen sensitizations and might be useful to direct dietary therapy in EoE.

In less than half a century, allergy, originally perceived as a rare disease, has become a major public health threat, today affecting the lives of more than 60 million people in Europe, and probably close to one billion worldwide, thereby heavily impacting the budgets of public health systems. More disturbingly, its prevalence and impact are on the rise, a development that has been associated with environmental and lifestyle changes accompanying the continuous process of urbanization and globalization. Therefore, there is an urgent need to prioritize and concert research efforts in the field of allergy, in order to achieve sustainable results on prevention, diagnosis and treatment of this most prevalent chronic disease of the 21st century.The European Academy of Allergy and Clinical Immunology (EAACI) is the leading professional organization in the field of allergy, promoting excellence in clinical care, education, training and basic and translational research, all with the ultimate goal of improving the health of allergic patients. The European Federation of Allergy and Airways Diseases Patients' Associations (EFA) is a non-profit network of allergy, asthma and Chronic Obstructive Pulmonary Disorder (COPD) patients' organizations. In support of their missions, the present EAACI Position Paper, in collaboration with EFA, highlights the most important research needs in the field of allergy to serve as key recommendations for future research funding at the national and European levels.Although allergies may involve almost every organ of the body and an array of diverse external factors act as triggers, there are several common themes that need to be prioritized in research efforts. As in many other chronic diseases, effective prevention, curative treatment and accurate, rapid diagnosis represent major unmet needs. Detailed phenotyping/endotyping stands out as widely required in order to arrange or re-categorize clinical syndromes into more coherent, uniform and treatment-responsive groups. Research efforts to unveil the basic pathophysiologic pathways and mechanisms, thus leading to the comprehension and resolution of the pathophysiologic complexity of allergies will allow for the design of novel patient-oriented diagnostic and treatment protocols. Several allergic diseases require well-controlled epidemiological description and surveillance, using disease registries, pharmacoeconomic evaluation, as well as large biobanks. Additionally, there is a need for extensive studies to bring promising new biotechnological innovations, such as biological agents, vaccines of modified allergen molecules and engineered components for allergy diagnosis, closer to clinical practice. Finally, particular attention should be paid to the difficult-to-manage, precarious and costly severe disease forms and/or exacerbations. Nonetheless, currently arising treatments, mainly in the fields of immunotherapy and biologicals, hold great promise for targeted and causal management of allergic conditions. Active involvement of all stakeholders, including Patient Organizations and policy makers are necessary to achieve the aims emphasized herein. ispartof: Clinical and Translational Allergy vol:2 issue:1 pages:21- ispartof: location:England status: published

These guidelines represent the updated consensus of experts in the field of immediate hypersensitivity reactions occurring during anesthesia. They provide a series of valid, widely accepted, effective, and easily teachable guidelines that are the fruit of current knowledge, research, and experience. The guidelines are based on the findings of international scientific research and have been implemented in France under the auspices of the French Society for Anaesthesia and Intensive Care (Societe Francaise d'Anesthesie et de Reanimation [SFAR]) and the French Society of Allergology (Societe Francaise d'Allergologie [SFA]). The members of the European Network for Drug Allergy approved the guidelines. This paper presents the most relevant clinical implications of the guidelines

Angio-oedema and urticaria can be symptoms of both allergic (IgE-mediated) and non-allergic drug hypersensitivity reactions. Non-allergic drug reactions, that may have a similar clinical presentation as allergic drug reactions, are not caused by an IgE-mediated immune mechanism. Because of unfamiliarity with non-allergic drug reactions and the unclear time course between drug use and reactions, the relationship with the responsible drug is often not recognized, leading to unnecessary patient risks. In the present article three patients with angio-oedema and urticaria as side effects of frequently used drugs (ACE-inhibitors, NSAIDs and betalactams) are presented and discussed. Patient A was a 69-year-old man with ACE-inhibitor induced angio-oedema. Patient B was a 40-year-old woman with urticaria and angio-oedema after ingestion of a NSAID caused by a non-allergic drug reaction. Patient C was a 54-year-old woman who developed an anaphylactic shock because of a type I allergy to betalactams.