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INTRODUCTION: Exercise induced anaphylaxis (EIA) denotes a range of disorders where anaphylaxis occurs in relation to physical exercise. Typical symptoms include flushing, pruritus, urticaria, angioedema, respiratory symptoms, gastro-intestinal symptoms, hypotension, and collapse during or after exercise. The far best described entity within EIA is food-dependent exercise-induced anaphylaxis (FDEIA), where symptoms only occur in combination with food intake. Frequency and predictability of symptoms vary, and some patients experience symptoms only if exercise is accompanied by other co-factors Areas covered: In the present review, we aimed to provide an overview of EIA, diagnostic workup, causes, management and discuss areas in need of further research. Expert opinion: Though rare, EIA is an entity that all allergists and practicing physicians should recognize. The pathophysiological and immunological mechanisms of EIA are largely unknown. Management is centered upon avoidance of eliciting factors, where emergency plans are individualized, except a mandatory prescription of an adrenaline auto-injector.

Background Sensitization to both inhalant and food allergens has been shown to be risk factors for development of asthma and rhinoconjunctivitis (RC). However, few studies have addressed the role of transient or persistent IgE sensitization to specific allergens in early life for later development of allergic diseases. The aim of this study was to explore the association between transient and persistent sensitization in early life and the development of asthma and RC at 6 and 14 years. Methods The Danish Allergy Research Center (DARC) cohort is a prospective non-interventional birth cohort study comprising 562 children. For the purpose of this study, we examined a subgroup of the original cohort with specific IgE measured at, at least 3 of 4 follow-ups between 3 and 18 months of age (n = 366). Multiple logistic regression models were used to investigate the association between transient and persistent early-life sensitization to groups of and to individual allergens and asthma and RC at 6 and 14 years compared to a reference group with no sensitization. Results Both transient early-life sensitization and persistent early-life sensitization to cow's milk or hen's egg proteins were associated with asthma (aOR 3.99[1.41-11.32] and 5.95[1.78-19.92]) and RC (aOR 2.94[1.19-7.28] and 6.18[1.86-20.53]) at 14 years, this association being driven mainly by sensitization to hen's egg. Transient early-life sensitization to house dust mite (HDM) had increased risk of asthma (aOR 3.80[1.17-12.41]) at 14 years. Conclusions Early transient IgE sensitization and persistent IgE sensitization to hen's egg were associated with asthma and RC at 14 years. Furthermore, sensitization to HDM was associated with asthma at 14 years.

This study evaluates adherence to adrenaline autoinjector prescriptions in a cohort of well-characterized anaphylaxis patients. The overall retrieval rate was 76% with the highest rate in patients with severe anaphylaxis. Special attention is needed in patients with unknown elicitors and in young adults, comprising the largest proportion of non-adherent patients. Trial registration No intervention performed. Retrospective data used with permission from the Danish Data Protection Agency and Regional Committees on Health Research Ethics

Background Atopic diseases are among the most common chronic diseases in adolescents and it is uncertain whether the prevalence of atopic diseases has reached a plateau or is still increasing. The use of the ISAAC (International Study of Asthma and Allergy in Childhood) questionnaire has provided comparable prevalence rates from many countries; whereas studies including clinical examinations and strict diagnostic criteria are scarce. We aimed to investigate the prevalence of atopic diseases, the pattern of sensitization and comorbidities at 14 years in a prospective birth cohort. Methods The children were examined eight times from birth to 14 years. Visits included questionnaire-based interviews, clinical examination, skin prick test and specific IgE. Results Follow-up rate at 14-years was 66.2%. The 12-month prevalence of any atopic disease was high (40.3%) mostly due to a high prevalence of rhinoconjunctivitis (32.8%) whereas the prevalence of asthma was 12.9% and of atopic dermatitis 8.1%. In children with at least one atopic disease 60% were sensitized while only 16% of those without atopic diseases were sensitized. The frequency of sensitization depended on the phenotype. Among children with rhinoconjunctivitis only, rhinoconjunctivitis with concomitant astma or atopic dermatitis or both 62.5%, 81.5%, 70% and 100% respectively were sensitized, whereas it was 7.7% and 33.3% of children with only asthma or atopic dermatitis. Conclusion The prevalence of rhinoconjunctivitis was high in adolescence. Children with rhinoconjunctivitis with and without comorbidities were frequently sensitized. Children with asthma without concomitant allergic rhinoconjunctivitis were rarely sensitized. This article is protected by copyright. All rights reserved.

Recent studies have demonstrated that the KIT D816V mutation is reliably detected in blood in adults with mastocytosis when using appropriate techniques [1–3]. Mutation analysis of blood has theref...

BACKGROUND: While much is known on childhood atopic diseases, knowledge about persistence of atopic diseases from childhood to adulthood is limited. We therefore aimed to study the clinical course of atopic diseases and type I sensitization prospectively in an unselected cohort of adolescents followed into adulthood.METHODS: A cohort of unselected 8th-grade school children (mean age 14 years) established in 1995 and followed up in 2010 were evaluated with questionnaire, clinical examination, skin prick tests and measurements of specific IgE.RESULTS: The lifetime prevalence of atopic diseases was high and increased significantly from adolescence (31%) to adulthood (57%); particularly allergic rhinitis increased with an incidence rate of 17.5/1000 person-years. Childhood predictors for adult allergic rhinitis were atopic dermatitis, asthma and asymptomatic sensitization to pollen and house dust mite. Among those with asymptomatic sensitization in adolescence, 53%-78% developed allergic rhinitis in adulthood. Furthermore, type I sensitization increased significantly from adolescence to adulthood mostly due to increased sensitization to pollen. Type I sensitization was found mainly in those with allergic rhinitis. A high number of adults had oral allergy symptoms due to the high number of birch pollen allergic individuals.CONCLUSION: Persistence of atopic diseases in adulthood is common, and a high proportion of the adult population is sensitized giving a high prevalence of allergic rhinitis. Many with asymptomatic sensitization in adolescence will develop allergic rhinitis in adult life. The focus should be on prevention of atopic diseases and sensitization already in childhood.

Mast cell activation disorders is a term proposed to cover diseases and conditions related to activation of mast cells and effects of mast cell mediators. In its broadest sense, the term encompasses a wide range of diseases from allergic asthma to rhinoconjunctivitis, urticaria, food allergy, anaphylaxis, mastocytosis, and other conditions where MC activation is contributing to the pathogenesis. This article focuses on clinical presentations, challenges, and controversies in pediatric mastocytosis and gives an overview of current knowledge and areas in need of further research.

The parallel epidemics of childhood asthma and obesity over the past few decades have spurred research into obesity as a risk factor for asthma. However, little is known regarding the role of asthma in obesity incidence. We examined whether early-onset asthma and related phenotypes are associated with the risk of developing obesity in childhood.This study includes 21 130 children born from 1990 to 2008 in Denmark, France, Germany, Greece, Italy, The Netherlands, Spain, Sweden and the UK. We followed non-obese children at 3-4 years of age for incident obesity up to 8 years of age. Physician-diagnosed asthma, wheezing and allergic rhinitis were assessed up to 3-4 years of age.Children with physician-diagnosed asthma had a higher risk for incident obesity than those without asthma (adjusted hazard ratio (aHR) 1.66, 95% CI 1.18-2.33). Children with active asthma (wheeze in the last 12 months and physician-diagnosed asthma) exhibited a higher risk for obesity (aHR 1.98, 95% CI 1.31-3.00) than those without wheeze and asthma. Persistent wheezing was associated with increased risk for incident obesity compared to never wheezers (aHR 1.51, 95% CI 1.08-2.09).Early-onset asthma and wheezing may contribute to an increased risk of developing obesity in later childhood. This work was partially supported by the Southern California Environmental Health Sciences Center (grant # P30ES007048) funded by the National Institute of Environmental Health Sciences [PI Gilliland]. Dr. Contreras was supported by a grant from the NIH T32ES013678. MEDALL and CHICOS Projects: The research leading to these results has received funding from the European Community’s Seventh Framework Program(Health–F2-grantagreements No. 261357 and 241604). Per cohort ABCD: Data of the Amsterdam Born Children and their Development cohort study used in this research was in part supported by funds from the Netherlands Organisation for Health Research and Development (ZonMw 40–00812-98–11010). The study sponsors had no role in study design, data analysis, interpretation of data, or writing of this report. BAMSE: We acknowledge all funding sources: The Swedish Research Council, The Swedish Heart and Lung Foundation, The Swedish Research Council for Working Life and Social Welfare, the Swedish Asthma and Allergy Association Research Foundation, The Swedish Research Council Formas, Stockholm County Council, and the European Commission’s Seventh Framework 29 Program Me DALL under grant agreement No.261357. We thank all the children and their parents for participating in the BAMSE cohort and the nurses and other staff members working in the BAMSE project. EDEN: We acknowledge all the funding sources for the EDEN study: Foundation for medical research (FRM), National Agency for Research (ANR), National Institute for Research in Public health (IRESP: TGIR cohorte santé 2008 program), French Ministry of Health (DGS), French Ministry of Research, INSERM Bone and Joint Diseases National Research (PRO-A) and Human Nutrition National Research Programs, Paris–Sud University, Nestlé, French National Institute for Population Health Surveillance (InVS),French National Institute for Health Education (INPES), the European Union FP7programmes (FP7/2007-2013, HELIX, ESCAPE, ENRIECO, Medall projects), Diabetes National Research Program (through a collaboration with the French Association of Diabetic Patients (AFD)), French Agency for Environmental Health Safety (now ANSES), Mutuelle Générale de l’Education Nationale a complementary health insurance (MGEN),French national agency for food security, French speaking association for the study ofdiabetes and metabolism (ALFEDIAM).We acknowledge the commitment of the EDEN mother-child cohort study group: I.Annesi-Maesano, JY. Bernard, J. Botton, M.A. Charles, P. Dargent-Molina, B. de Lauzon-Guillain, P. Ducimetière, M. de Agostini, B. Foliguet, , A. Forhan, X. Fritel, A. Germa, V.Goua, R. Hankard, B. Heude, M. Kaminski, B. Larroque†, N. Lelong, J. Lepeule, G.Magnin, L. Marchand, C. Nabet, F. Pierre, R. Slama, M.J. Saurel-Cubizolles, M.Schweitzer, O. Thiebaugeorges.The Generation R Study:The Generation R study is made possible by financial support from the Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam, the Netherlands Organization for Health Research and Development (ZonMw), the Netherlands Organisation for Scientific Research (NWO), the Ministry of Health, Welfareand Sport and the Ministry of Youth and Families. The project received funding from the European Union's Horizon 2020 research and innovation programme (LIFECYCLE project, grant agreement no 733206; 2016), the European Research Council (ERC-2014-CoG-648916) and from cofunded ERA-Net on Biomarkers for Nutrition and Health (ERAHDHL), Horizon 2020 (grant agreement no 696295; 2017), ZonMW The Netherlands (no529051014; 2017), Science Foundation Ireland (no SFI/16/ERA-HDHL/3360), and the European Union (ALPHABET project).The researchers are independent from the funders. The study sponsors had no role in study design, data analysis, interpretation of data, or writing of this report. INMA: Data used for this research was provided by the INMA-Environment and Childhood Project (www.proyectoinma.org). This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176 and CB06/02/0041), Spanish Ministry of Health (FIS-PIO41436, PI06/0867, PI081151, and FIS-FEDER 03/1615, 04/1112,04/1931, 05/1079, 05/1052, 06/1213, 07/0314 and 09/02647), Generalitat de Catalunya-CIRIT 1999SGR00241, the Conselleria de Sanitat Generalitat Valenciana, Department of Health of the Basque Government (2005111093 and 2009111069), the ProvincialGovernment of Gipuzkoa (DFG06/004 and DFG08/001).KOALA: The collection of the data from the KOALA Birth Cohort Study used in this analysis was financially supported by Friesland Foods (now Friesland Campina),Netherlands Asthma Foundation (grant numbers 3.2.07.022 and 3.2.03.48), Netherlands Heart Foundation (grant number 2014 T037, the Netherlands Organization for Health Research and Development (Zon Mw Prevention Program number 1.210-00-090), Triodos Foundation, Phoenix Foundation, Raphaël Foundation, Iona Foundation, Foundation forthe Advancement of Heilpedagogie, all in the Netherlands. MAS:The MAS birth cohort was funded by grants from the German Federal Ministry ofEducation and Research (BMBF; reference numbers 07015633, 07 ALE 27, 01EE9405/5,01EE9406) and the German Research Foundation (DFG; reference number KE 1462/2-1).PIAMA: The PIAMA study has been funded by The Netherlands Organisation for Health Research and Development; The Netherlands Organisation for Scientific Research; The Netherlands Asthma fund; The Netherlands Ministry of Spatial Planning Housing, and the Environment; and The Netherlands Ministry of Health, Welfare and Sport. RHEA: The Rhea project was financially supported by European projects (EU FP6-003-Food-3-NewGeneris -Contract No16320, EU FP6 STREP Hiwate -Contract No36224,EU FP7 ENV.2007.1.2.2.2. Project No 211250 Escape, EU FP7-2008-ENV-1.2.1.4 Envirogenomarkers Contract No226756, EU FP7-HEALTH-2009-single stage CHICOS Contract No241604, EU FP7 ENV.2008.1.2.1.6. Proposal No 226285 ENRIECO, EU-FP7,Proposal No 264357 MeDALL, EU- FP7-HEALTH-2012 Proposal No 308333 HELIX),and the Greek Ministry of Health (Program of Prevention of obesity and neurodevelopmental disorders in preschool children, in Heraklion district, Crete, Greece:2011-2014; “Rhea Plus”: Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012-2015).ROBBIC: Data of the Rome cohort was in part supported byfunds from the Italian Ministry of Health (Programma speciale ex art. 12, comma 2, lettera b) del D. Lgs. 502/92,2001, 2003). We thank all the fields workers and the families for their contribution to thestudy. SWS: We thank the members of the Southampton Women's Survey Study group and the many participants in the SWS for their contribution to the study. The Southampton Women’s Survey is supported by grants from the Medical Research Council, British Heart Foundation, Food Standards Agency, British Lung Foundation, Arthritis Research UK, NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, and the European Union's Seventh Framework Programme (FP7/2007-2013), project Early Nutrition under grant agreement n°289346.

Background Most published studies on anaphylaxis are retrospective or register based. Data on subsequent diagnostic workup are sparse. We aimed to characterize patients seen with suspected anaphylaxis at the emergency care setting (ECS), after subsequent diagnostic workup at our Allergy Center (AC). Methods Prospective study including patients from the ECS, Odense University Hospital, during May 2013-April 2014. Possible anaphylaxis cases were daily identified based on a broad search profile including history and symptoms in patient records, diagnostic codes and pharmacological treatments. At the AC, all patients were evaluated according to international guidelines. Results Among 226 patients with suspected anaphylaxis, the diagnosis was confirmed in 124 (54.9%) after diagnostic workup; 118 of the 124 fulfilled WAO/EAACI criteria of anaphylaxis at the ECS, while six were found among 46 patients with clinical suspicion but not fulfilling the WAO/EAACI criteria at the ECS. The estimated incidence rate of anaphylaxis was 26 cases per 100 000 person-years and the one-year period prevalence was 0.04%. The most common elicitor was drugs (41.1%) followed by venom (27.4%) and food (20.6%). In 13 patients (10.5%), no elicitor could be identified. Mastocytosis was diagnosed in 7.7% of adult patients and was significantly associated with severe anaphylaxis. Atopic diseases were significantly associated only with food-induced anaphylaxis. Cofactors were present in 58.1% and were significantly associated with severe anaphylaxis. Conclusion A broad search profile in the ECS and subsequent diagnostic workup is important for identification and classification of patients with anaphylaxis. Evaluation of comorbidities and cofactors is important.

Background Vaccination with Bacillus Calmette-Guerin (BCG) is used in many countries as protection against tuberculosis. Studies have suggested that BCG may also have non-specific effects, reducing non-tuberculosis mortality, morbidity, and atopic manifestations. In this study we evaluated the effect of neonatal BCG vaccination on allergic sensitization and suspected food allergy at 13 months of age. Methods The Danish Calmette Study was conducted from 2012-2015 at three Danish hospitals. Within 7 days of birth, the 4262 newborns of 4184 included mothers were randomized 1:1 to BCG or to a no-intervention control group. Exclusion criteria were gestational age 0.35 kUA/l) was found in 55/743 (7.4%) children in the BCG group and 50/627 (8.0%) of the control group (risk ratio 0.94 (0.65 to 1.36)). Conclusion In this randomized clinical trial neonatal BCG had no significant effect on suspected food allergy or on sensitization at 13 months of age. This article is protected by copyright. All rights reserved.

Background: Rhinoconjunctivitis is a global health problem and one of the most common chronic conditions in children. Development of rhinoconjunctivitis depends on both genetic and environmental factors. Many studies have investigated rhinoconjunctivitis, but only few studies have evaluated the risk factors for non-allergic rhinoconjunctivitis in children finding family history of atopic diseases and gender to be of importance. The aim of this study was to investigate possible risk factors in early life for rhinoconjunctivitis, allergic as well as non-allergic, in adolescence. Methods: The children in the Danish Allergy Research Center cohort were examined eight times from birth to 14 years of age. Visits included questionnaire-based interview, clinical examination, skin prick test and specific IgE. We used univariate and multivariate logistic regression to investigate the relationship between early-life risk factors and the development of rhinoconjunctivitis, allergic as well as non-allergic, in adolescence. Results: Follow-up rate at 14-years was 66.2%. The prevalence of rhinoconjunctivitis was 32.8%. Family history of atopic diseases (aOR 2.25), atopic dermatitis (aOR 3.24), food allergy (aOR 3.89), early sensitization to inhalant and food allergens (aOR 2.92 and aOR 3.13) and male gender (aOR 1.90) were associated with allergic rhinoconjunctivitis but not with non-allergic rhinoconjunctivitis. Early environmental tobacco exposure was inversely associated with rhinoconjunctivitis (aOR 0.42), allergic (aOR 0.47) as well as non-allergic (aOR 0.43). Conclusion: Different patterns of associations were revealed when stratifying rhinoconjunctivitis in allergic and non-allergic suggesting that allergic rhinoconjunctivitis and non-allergic-rhinoconjunctivitis are different phenotypes.

We present three cases with anaphylaxis after injection of a depot corticosteroid. First, the steroid was suspected as the elicitor, but after evaluation the excipient macrogol was found to be the elicitor. One of the patients had reactions to several unrelated drugs. Increased awareness of anaphylaxis to excipients such as macrogols is needed, especially when allergy tests for the active drug is negative and in patients with a history of repeated anaphylaxis to seemingly unrelated drugs. To establish the correct diagnosis it is important to test with the exact formulation of the culprit drug, as well as all the ingredients including excipients.