Immediate and non-immediate hypersensitivity reactions to iodinated contrast media (ICM) have been reported to occur in a frequency of about 0.5-3% of patients receiving non-ionic ICM. The diagnosis and management of these patients is controversial among guidelines published by various national and international scientific societies, with recommendations ranging from avoidance or premedication to drug provocation test. This position paper aims to give recommendations for the management of patients with ICM hypersensitivity reactions and analyze controversies in this area. Skin tests are recommended as the initial step for diagnosing patients with immediate and non-immediate hypersensitivity reactions; besides, they may also help guide on tolerability of alternatives. Drug provocation test is the gold-standard; although, as it is a risky procedure, the decision for performing it needs to be taken based on a risk-benefit analysis. Another source of controversy is the role of in vitro tests for diagnosis and pretreatment for preventing reactions.
The basophil activation test (BAT) is a functional assay that measures the degree of degranulation following stimulation with allergen or controls by flow cytometry and is directly correlated with histamine release. From the bell-shaped curve resulting from BAT in allergic patients, basophil reactivity (given by %CD63+ basophils) and basophil sensitivity (given by EC50 or similar) are the main outcomes of the test. BAT takes into account all characteristics of IgE and allergen and thus can be more specific than sensitization tests in the diagnosis of allergic disease. BAT reduces the need for in vivo procedures, such as intradermal tests and allergen challenges, which can cause allergic reactions of unpredictable severity. As it closely reflects the patients’ phenotype, it can potentially be used to monitor the natural resolution of food allergies and to predict and monitor clinical response to immunomodulatory treatments, such as allergen-specific immunotherapy and biologicals. Clinical application of BAT requires analytical validation, clinical validation, standardization of procedures and quality assurance to ensure reproducibility and reliability of results. Currently, efforts are ongoing to establish a platform that could be used by laboratories in Europe and in the USA for certification.
Nanotechnology is science, engineering, and technology conducted at the nanoscale, which is about 1 to 100 nanometers. It has led to the development of nanomaterials, which behave very differently compared with materials with larger scales and can be applied in a wide range of applications in biomedicine. The physical and chemical properties of materials of such small compounds depend mainly on the size, shape, composition, and functionalisation of the system. Nanoparticles, carbon nanotubes, liposomes, polymers, dendrimers, nanogels, among others, can be nanoengineeried for controlling all parameters, including their functionalisation with ligands, which provide the desired interaction with the immunological system. However, undesired issues related to their toxicity and hypersensitivity responses have impeded more rapid health applications. Through interactions with the immune system, some of these nanostructures show promising applications as vaccines and diagnostics tools. Dendrimeric Antigens, Nanoallergens, and nanoparticles are potential tools for the in vitro diagnosis of allergic reactions. Glycodendrimers, liposomes, polymers, and nanoparticles have shown interesting applications in immunotherapy. There are wide panels of structures accessible, and controlling their physico-chemical properties would allow the obtainment of safer and more efficient compounds for clinical applications goals, either in diagnosis or treatment.
Medical Algorithm: Early Introduction of Food Allergens in High Risk PopulationsHelen R Fisher,1,2 Gideon Lack,1,2,3 Graham Roberts,4,5,6 Henry T Bahnson,7 George Du Toit.1,2,31Paediatric Allergy Group, Department of Women and Children’s Heath, School of Life Course Sciences, King’s College London, London, United Kingdom2Paediatric Allergy Group, Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King’s College London, London, United Kingdom.3Children’s Allergy Service, Guy’s and St. Thomas’ NHS Foundation Trust, London, United Kingdom.4The David Hide Asthma and Allergy Research Centre, St Mary’s Hospital, Newport, UK.5NIHR Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.6Faculty of Medicine, Clinical and Experimental Sciences, Human Development in Health Academic Units, University of Southampton, Southampton, UK.7Immune Tolerance Network, Benaroya Research Institute, Seattle, WashingtonCorresponding Authour:Professor George Du ToitPaediatric AllergyBlock B, South WingSt Thomas’ HospitalLondonSE1 7EHTel: 0207 188 9784Email: [email protected] Count: 602Tables: 0Figures: 1Oral Tolerance Induction (OTI) is the only RCT-proven effective intervention for preventing childhood food allergy.(1) OTI to peanut is effective in a general population, with the greatest effect, 81% RRR, noted in the high-risk population.(2) OTI also reduced egg allergy in the general population.(1) Many governmental and allergy societies now recommend introducing peanut in infancy and some suggest other foods, such as well-cooked egg, are also introduced. Choosing which infants should undergo OTI, at what age, to which foods, and under which circumstances is critical for successful OTI prevention in populations where food allergy is a public health concern.Infants with eczema are at increased risk of food allergy but infants from the general population are also at risk and contribute most cases at a population level. Risk of food sensitisation or food allergy increase with age; OTI is most likely to be successful when started in early infancy. Oral tolerance induction from 4 months of age, when completed using standard foods, is safe for nutrition, growth and general child health outcomes (3). Commencing multiple food OTI at 4 months of age, has no detrimental effect on established breastfeeding.(4) All children should adopt a diverse weaning diet, including allergenic foods such as well-cooked egg and peanut, as soon as weaning commences. High risk children should not delay weaning but start weaning and actively include peanut and well-cooked egg, as soon as developmentally ready; usually at about 4 months of age (Fig 1).A 2g/week dosing regime of peanut and well-cooked egg in early infancy is more effective in inducing oral tolerance than later introduction.(5) A lower dosing regime has not been shown to be effective in preventing allergy but, importantly, does not increase allergy risk above that of children who introduce allergenic foods in later infancy.(4) There are limited data regarding the efficacy of OTI to other allergenic foods, or the dose required.(1) All infants should aim to consume about 2g of peanut protein and well-cooked egg per week; parents of high-risk infants should give these amounts more diligently. Given the benefit observed for peanut and egg, it is reasonable for all weaning infants to additionally incorporate 2g of other common and nutritious food allergens; cow’s milk (e.g. as yoghurt), wheat, fish and sesame.Whether children should undergo allergy testing and/or have their first feed of peanut under medical supervision is contested. This cautious approach, potentially requiring large numbers of children to access specialist allergy care, must be balanced against the risks of severe allergic reaction, particularly as most allergic reactions occur on first oral exposure. RCTs of OTI using whole foods had no cases of anaphylaxis on first exposure (4, 6) although anaphylaxis has occurred to OTI using pasteurised whole egg powder.(7) Children with no personal food allergy risk factors do not require testing prior to, or medical supervision during, their first consumption of peanut or well-cooked egg. Children with moderate to severe eczema, or with an existing food allergy should undergo allergy testing +/- OFC at a specialist allergy centre(8), if doing so would not cause undue delay to OTI. It is likely that rapid access to allergy services will be further compromised as a consequence of the COVID-19 pandemic. It may however be that access to SpIgE is available through GP or paediatrician which, if ≥0.35KiU/L, will require referral for OFC. If negative (<0.35KiU/L) the food may be introduced at home following precautionary measures for the first feed: child is well; parent is aware of the signs of IgE mediated reaction has, access to medical support if required and age-appropriate form of the food is given incrementally (Figure 1).
Background: Multiplex tests allow for measurement of allergen-specific IgE responses to multiple allergen extracts and components and have several advantages for large cohort studies. Due to significant methodological differences, test systems are difficult to integrate in meta-analyses/systematic reviews since there is a lack of datasets with direct comparison. We aimed to create models for statistical integration of allergen-specific IgE to peanut/tree nut allergens from three IgE-test platforms. Methods: Plasma from Canadian and Austrian children with peanut/tree nut sensitization and a cohort of sensitized, high-risk, pre-school asthmatics (total n=166) were measured with three R&D multiplex IgE test platforms: Allergy Explorer, ALEX (Macro Array Dx), MeDALL-chip (Mechanisms of Development of Allergy) (Thermo Fisher), and EUROLINE (EUROIMMUN). Skin prick test (n=51) and ImmunoCAP (n=62) results for extracts were available in a subset. Regression models (Multivariate Adaptive Regression Splines, local polynomial regression) were applied if >30% of samples were positive to the allergen. Intra-test correlations between PR-10 and nsLTP allergens were assessed. Results: Using two regression methods, we demonstrated the ability to model allergen-specific relationships with acceptable measures of fit (r2=94-56%) for peanut and tree nut sIgE testing at the extract and component-level, in order from highest to lowest: Ara h 2, Ara h 6, Jug r 1, Ana o 3, Ara h 1, Jug r 2, Cor a 9. Conclusion: Our models support the notion that conversion is reasonably possible between sIgE multiplex platforms for allergen extracts and components and may provide options to aggregate data for future meta-analysis.
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 sub-sections 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.