Pistachio and cashew nut allergy in childhood: Predictive factors towards development of a decision tree.

BACKGROUND: Pistachio and cashew nut, which belong to the same botanical family, are tree nuts that induce serious allergic reactions. OBJECTIVE: We aimed to determine the predictive factors for pistachio and cashew nut reactivity during oral food challenge (OFC). METHODS: A total of 112 pistachio and/or cashew nut sensitized children, aged 58.45 (IQR:40.38-88.32) months, were included. Cutoff values and probability curves for skin prick test (SPT), sIgE, sIgE/Total IgE that predict reactivity were determined for pistachio and cashew nut. Additionally, a diagram was created that can be useful while making a decision for OFC based on SPT and sIgE values. RESULTS: A total of 73 patients underwent OFC with pistachio and/or cashew nut. Twelve children with current anaphylaxis history were not challenged and accepted as allergic. SPT was the only predictive factor for positive pistachio/ cashew nut OFC. According to area under curve (AUC) analysis, SPT was more predictive than sIgE and sIgE/Total IgE both for pistachio and cashew nut. Optimal cutoff values according to "Youden index" for pistachio SPT, sIgE, and sIgE/ Total IgE were 7.25 mm, 4.14 kUA/L, and 1.32%, respectively. And those values for cashew nut SPT, sIgE, and sIgE/Total IgE were 6.25 mm, 1.125 kUA/L, and 3.30%, respectively. The diagram showed that SPT predicted the reactivity together with sIgE better than only the SPT values. CONCLUSION: SPT was the best predictor for reactivity both for pistachio and cashew nut. Combined use of SPT and sIgE may improve the prediction of reactivity at pistachio and cashew nut OFCs in children.

Biologic Agents for the Treatment of Anaphylaxis.

Several biologic therapies and new devices are emerging as potential preventive treatment of anaphylaxis. However, adrenaline (epinephrine) is still the first-line treatment of any type of anaphylaxis. Biologic drugs, such as omalizumab, although not US Food and Drug Administration approved for anaphylaxis, have been used as therapeutic adjuvants in the preventive treatment of anaphylaxis, but cost-effectiveness should be considered individually.

Hymenoptera venom allergy among children in Italy: time for pediatricians to take action.

Hymenoptera venom allergy (HVA) is one of the most frequent causes of anaphylaxis following a bee, vespid or ant sting. Real-life data regarding the management of HVA in children are lacking. To address this unmet need, we carried out a survey defining the current management of HVA in children among pediatric allergists in Italy. Educational investments on the improvement of the management of pediatric patients with HVA are urgently needed, and our analysis represents a relevant instrument in targeting a roadmap with this aim. The time for pediatric allergists to take action has come, and a task force from the Rare Allergic Diseases Commission of the Italian Society of Pediatric Allergy and Immunology is working on the topic to improve pediatricians' knowledge and optimize the care of these patients.

Identifying and managing patients at risk of severe allergic reactions to food: Report from two iFAAM workshops.

Food allergy affects a small but important number of children and adults. Much of the morbidity associated with food allergy is driven by the fear of a severe reaction and fatalities continue to occur. Foods are the commonest cause of anaphylaxis. One of the aims of the European Union-funded Integrated Approaches to Food Allergen and Allergy Risk Management (iFAAM) project was to improve the identification and management of children and adults at risk of experiencing a severe reaction. A number of interconnected studies within the project have focused on quantifying the severity of allergic reactions; the impact of food matrix, immunological factors on severity of reactions; the impact of co-factors such as medications on the severity of reactions; utilizing single-dose challenges to understand threshold and severity of reactions; and community studies to understand the experience of patients suffering real-life allergic reactions to food. Associated studies have examined population thresholds and co-factors such as exercise and stress. This paper summarizes two workshops focused on the severity of allergic reactions to food. It outlines the related studies being undertaken in the project indicating how they are likely to impact on our ability to identify individuals at risk of severe reactions and improve their management.

How to cope with food allergy symptoms?

PURPOSE OF REVIEW: Food allergy symptoms may involve a wide variety of organs (skin, gastrointestinal tract, and eyes) and systems (respiratory, circulatory, and neurological). They are often associated. Their severity ranges from mild to potentially life-threatening reactions and the presentation from acute to chronic. RECENT FINDINGS: Food allergies have been the focus of multiple studies, position papers, and guidelines in recent years. They have defined an approach in classifying symptoms as mild to anaphylactic, distinguishing objective from subjective symptoms, and describing their heterogeneity, specific phenotypes or syndromes (e.g., lipid transfer protein syndrome or pollen food syndrome). Cofactors can also influence food allergy reactions. Symptoms of non-IgE-gastrointestinal food allergies, illustrated by eosinophilic esophagitis and food-protein-induced enterocolitis syndrome, are also now better understood and defined. Improvement in the knowledge of food allergy symptoms is crucial for correct diagnosis and a personalized treatment approach. SUMMARY: Through a better description and understanding of symptoms, the diversity of food allergies is now better known. The next step is to harmonize symptom assessment not only for clinicians but also for patients, researchers, and public health stakeholders, to describe food allergy phenotypes and their underlying mechanisms and endotypes, to develop targeted management.

The urgent need for a harmonized severity scoring system for acute allergic reactions.

The accurate assessment and communication of the severity of acute allergic reactions are important to patients, clinicians, researchers, the food industry, and public health and regulatory authorities. Severity has different meanings to different stakeholders with patients and clinicians rating the significance of particular symptoms very differently. Many severity scoring systems have been generated, most focusing on the severity of reactions following exposure to a limited group of allergens. They are heterogeneous in format, none has used an accepted developmental approach, and none has been validated. Their wide range of outcome formats has led to difficulties with interpretation and application. Therefore, there is a persisting need for an appropriately developed and validated severity scoring system for allergic reactions that work across the range of allergenic triggers and address the needs of different stakeholder groups. We propose a novel approach to develop and then validate a harmonized scoring system for acute allergic reactions, based on a data-driven method that is informed by clinical and patient experience and other stakeholders' perspectives. We envisage two formats: (i) a numerical score giving a continuum from mild to severe reactions that are clinically meaningful and are useful for allergy healthcare professionals and researchers, and (ii) a three-grade-based ordinal format that is simple enough to be used and understood by other professionals and patients. Testing of reliability and validity of the new approach in a range of settings and populations will allow eventual implementation of a standardized scoring system in clinical studies and routine practice.

Immunogenicity assessment during the development of protein therapeutics.

OBJECTIVE: Here we provide a critical review of the state of the art with respect to non-clinical assessments of immunogenicity for therapeutic proteins. KEY FINDINGS: The number of studies on immunogenicity published annually has more than doubled in the last 5 years. The science and technology, which have reached a critical mass, provide multiple of non-clinical approaches (computational, in vitro, ex vivo and animal models) to first predict and then to modify or eliminate T-cell or B-cell epitopes via de-immunization strategies. We discuss how these may be used in the context of drug development in assigning the immunogenicity risk of new and marketed therapeutic proteins. SUMMARY: Protein therapeutics represents a large share of the pharma market and provide medical interventions for some of the most complex and intractable diseases. Immunogenicity (the development of antibodies to therapeutic proteins) is an important concern for both the safety and efficacy of protein therapeutics as immune responses may neutralize the activity of life-saving and highly effective protein therapeutics and induce hypersensitivity responses including anaphylaxis. The non-clinical computational tools and experimental technologies that offer a comprehensive and increasingly accurate estimation of immunogenic potential are surveyed here. This critical review also discusses technologies which are promising but are not as yet ready for routine use.

Adjuvants for allergy immunotherapeutics.

Allergic diseases are reaching epidemic proportions in developed countries. In particular, food allergy is increasing in prevalence and severity, thus becoming an important socioeconomic burden. Numerous cell types and cell populations, which form an intricate and balanced network, are involved in an immune response. This balance is occasionally disturbed, leading to the onset of different diseases, such as allergic diseases. Antihistamines and corticosteroids provide some degree of relief from the symptoms of allergic conditions. However, the only treatment that can revert the disease is immunotherapy. Nevertheless, specific immunotherapy has at least 2 major drawbacks: it is time-consuming, and it can produce local and even systemic allergic side effects. Immunotherapy's potential goes beyond our current knowledge of the immune response; nevertheless, we can still design strategies to reach a safer immune modulation for treating allergies. This review deals with the use of adjuvants to reduce the undesirable side effects associated with specific allergen immunotherapy. For example, nanoparticles used as immunoadjuvants are offering promising results in preclinical assays.

Clinical and laboratory features, and quality of life assessment in wheat dependent exercise-induced anaphylaxis patients from central China.

Wheat dependent exercise-induced anaphylaxis (WDEIA) is a rare but potentially severe food allergy caused by the combination of wheat ingestion and physical exercise. The impact of WDEIA on quality of life (QOL) is unclear. This study characterized the clinical and laboratory features and investigated the QOL in WDEIA patients from Central China. Twenty-eight WDEIA patients were analyzed, and QOL was measured by validated Chinese version Food Allergy Quality of Life Questionnaire-Adult Form (FAQLQ-AF) and Food Allergy Independent Measure (FAIM) after obtaining the diagnosis. The results showed that half of the patients were females. The median onset age was 37 years old. The symptoms occurred within 1 h after wheat ingestion (26/28). Symptoms of anaphylaxis included cutaneous (26/28), respiratory (11/28), gastro-intestinal (5/28) and cardiovascular manifestations (27/28). Skin prick tests were positive to salt soluble (89.3%) and salt insoluble wheat allergen extracts (100%). Positive rate to wheat, gluten and omega-5 gliadin specific IgE was 64.3%, 92.9% and 92.9% respectively. Specific IgE to omega-5 gliadin with a cut-off value 0.83 KU/L offered highly efficient diagnostic criterion for WDEIA (sensitivity: 89.3%; and specificity: 88.9%). The mean scores of FAQLQ-AF and FAIM were 4.70 and 4.98 respectively and level of anti-omega-5 gliadin IgE had positive correlations with FAQLQ scores. Thereby, WDEIA is commonly found in mid-age adults. In most cases, multi-organs especially skin and cardiovascular systems are involved. Salt insoluble wheat allergen skin test and serum specific IgE to gluten and omega-5 gliadin help to diagnose WDEIA. QOL in WDEIA patients is severely impaired.

Introduction of peanuts in younger siblings of children with peanut allergy: a prospective, double-blinded assessment of risk, of diagnostic tests, and an analysis of patient preferences.

BACKGROUND: The prevalence of peanut allergy in younger siblings of children with peanut allergy has been reported between 7% and 8.5%, but the anaphylactic risk at the time of introduction is currently unknown, which limits our ability to best counsel parents on this issue. OBJECTIVE: To determine the risk of anaphylaxis and working parameters of allergy testing in this context. METHODS: One hundred and fifty-four peanut-naïve younger siblings of peanut-allergic children underwent double-blinded skin testing, followed by parent-led peanut introduction. Questionnaires were dispensed to parents to investigate preferences with regard to peanut introduction in this subgroup. RESULTS: Eight participants (5.2%) presented unequivocal IgE-mediated reactions to peanut upon introduction, including five anaphylaxes. These participants were significantly older compared to the rest of the cohort (median 4.0 vs 1.9 years, P = 0.04). The negative predictive value of skin prick test with peanut extract and peanut butter and of specific IgE was 99%, 100%, and 100%, respectively. Six peanut-tolerant participants had positive peanut allergy tests. The option of introducing at home without prior skin testing was associated with high levels of anxiety (median 8.4 on 10-point Likert scale) when compared to supervised introduction (median 3.8, P < 0.0001) or home introduction after negative skin test (median 4.3, P < 0.0001). CONCLUSIONS: There is an increased risk of anaphylaxis upon peanut introduction in siblings of children with peanut allergy, and parents are reluctant to introduce at home without testing. Allergy testing prior to introduction is negative in over 90% of cases and carries a high negative predictive value.

Assessment of the Allergenic Potential of Transgenic Wheat (Triticum aestivum) with Reduced Levels of ω5-Gliadins, the Major Sensitizing Allergen in Wheat-Dependent Exercise-Induced Anaphylaxis.

The ω5-gliadins are the major sensitizing allergens in wheat-dependent exercise-induced anaphylaxis (WDEIA). In this study, two-dimensional immunoblot analysis was used to assess the allergenic potential of two transgenic wheat lines in which ω5-gliadin genes were silenced by RNA interference. Sera from 7 of 11 WDEIA patients showed greatly reduced levels of immunoglobulin E (IgE) reactivity to ω5-gliadins in both transgenic lines. However, these sera also showed low levels of reactivity to other gluten proteins. Sera from three patients showed the greatest reactivity to proteins other than ω5-gliadins, either high-molecular-weight glutenin subunits (HMW-GSs), α-gliadins, or non-gluten proteins. The complexity of immunological responses among these patients suggests that flour from the transgenic lines would not be suitable for individuals already diagnosed with WDEIA. However, the introduction of wheat lacking ω5-gliadins could reduce the number of people sensitized to these proteins and thereby decrease the overall incidence of this serious food allergy.

Factors impacting parental burden in food-allergic children.

AIM: This study aims to determine factors impacting the parental burden in immunoglobulin E (IgE)-mediated food-allergic children (FAC), focusing on attitudes towards adrenaline autoinjectors (AAIs). METHODS: Questionnaires were sent to parents of diagnosed IgE-mediated FAC attending follow-up allergy clinic appointments at two Sydney hospitals in May-September 2013. The questionnaires ascertained parental attitudes, confidence and knowledge regarding AAIs and included the validated, Food Allergy Quality of Life-Parental Burden (FAQL-PB) questionnaire. RESULTS: The response rate was 68%. Of FAC, 62% were male aged 1-17 years (median 6.0). There was a high proportion of children with multiple food allergies (52% allergic to >2 foods), coexistant eczema (85%) and asthma (54%). Sixty-three per cent reported a past history of anaphylaxis and 42% reported reactions in the last 6 months. AAI had been prescribed for 84%. FAC with a history of anaphylaxis were more likely to have had an AAI prescribed (P < 0.0001). There was no difference in FAQL-PB mean scores with age or AAI prescription status. The PB score was greater if the parent had administered the AAI (P = 0.02) and where the child was allergic to >2 foods (P < 0.0001).The Ninety per cent of parents reported that the AAI increased or did not change the child's quality of life, the family or FACs freedom. Three per cent of parents whose FAC children were prescribed an AAI reported increased stress related to AAI prescription. CONCLUSION: Severity of food allergy, number of food allergens and past anaphylaxis rather than prescription of an AAI appear to be major influences on parental burden.

Ant venom immunotherapy in Australia: the unmet need.

Jack jumper ant (JJA) venom allergy is an important cause of anaphylaxis in south-eastern Australia. The efficacy and real-world effectiveness of JJA venom immunotherapy (VIT) to prevent anaphylaxis in allergic patients are now well established, with an evidence base that is at least equivalent to that supporting VIT for allergy to other insect species. The tolerability and safety of JJA VIT are comparable with those of honeybee VIT.

Anaphylaxis: opportunities of stratified medicine for diagnosis and risk assessment.

The risk to develop anaphylaxis depends on the sensitization pattern, the proportion of the involved immunoglobulin classes, the avidity and affinity of immunoglobulins to bind an allergen, characteristics of the allergen, the route of allergen application, and, last but not least, the presence of cofactors of anaphylaxis. To be able to calculate the risk to develop anaphylaxis and to anticipate the severity of the reactions under certain conditions, it is necessary to understand how all these factors interact with each other. Important progress for risk assessment in anaphylaxis is based on component-resolved stratified diagnostics, which allow to (i) determine a patient's sensitization pattern on a molecular basis, (ii) correlate clinical responses to defined sensitization patterns, and (iii) better identify cross-reactive allergens. Together with the increasing knowledge regarding the role and mode of action of cofactors of anaphylaxis, these data pave the way to unscramble the complex interactions determining the clinical relevance of sensitizations, the risk of anaphylaxis, and the severity of reactions. As a consequence, this understanding allows to better determine the individual risk in response to an identified allergen and results in more specific advices and education for our patients to prevent further life-threatening anaphylactic reactions.

Management of acute food allergic reactions by general practitioners.

BACKGROUND: Food is one of the leading causes of anaphylaxis. In the Netherlands, patients visit a general practitioner (GP) as often as an emergency department (ED) in case of an acute food allergic reaction. So far, the management of food allergic reactions by GPs has not been investigated. Therefore, we explored the management of acute food allergic reactions by GPs regarding specific treatment, observation period, prescription of emergency medication to treat new episodes, diet advices and referral to a specialist. METHODS: A questionnaire containing three hypothetical cases (two anaphylactic and one mild case) with questions about their management was sent to 571 GPs. RESULTS: Overall, treatment choice was dependent on the severity of the reaction (mild vs. anaphylaxis, P < .001). However, epinephrine was used for treatment of anaphylaxis with mainly respiratory symptoms in only 27% and for anaphylaxis with mainly cardiovascular symptoms in 73%. At discharge, the percentages for prescription of self-injectable epinephrine were 53% and 77%, respectively. A short observation period of <2 hours was advised by 42% of general practitioners in case of anaphylaxis. CONCLUSIONS: Treatment of food induced anaphylaxis by GPs appears to be suboptimal: a considerable number of patients would not be treated with epinephrine for the acute reaction (especially anaphylactic cases with respiratory symptoms), the observation period chosen by GPs was often too short and self-injectable epinephrine was not always prescribed at discharge to treat possible new episodes. Education programs are needed to increase the awareness of GPs to recognize and treat anaphylactic reactions.

Risk assessment of immediate systemic reactions from skin tests with ß-lactam antibiotics.

BACKGROUND: Some clinical studies have demonstrated that skin tests for ß-lactam antibiotics may cause more adverse reactions than skin tests for common allergens. OBJECTIVE: To assess the risk of systemic reactions from penicillin skin testing, based on a pre-test categorization of patients, in order to establish an appropriate strategy for preempting and dealing with cases. METHODS: A case series of 175 patients with a suspected allergy to penicillin was reviewed, and patients were classified as having a low or high probability of allergic sensitization to penicillin, according to their clinical history. For every group, the rate and the increase in the relative risk (RRI) of systemic reactions by skin testing were calculated. The results were compared to those reported in the available literature. RESULTS: In our case series of 175 patients, 52 were classified as having a high probability of being allergic to penicillin, according to their clinical history. Five systemic reactions to skin testing were observed, and these were exclusively in this group (9.61%, RRI = 479). In agreement with the literature, patients with a high likelihood of penicillin allergy showed an increase of up to 10% in the occurrence of systemic reactions at skin testing; in patients who had had severe allergic reactions, this figure was up to 20%. CONCLUSIONS: The RRI of systemic reactions by skin testing is proportional to the pre-test probability of a true immediate hypersensitivity reaction to ß-lactam antibiotics. In the present case series, only patients with high pre-test probability were at risk, and this group should therefore be skin tested and monitored in a hospitalization regimen, where resuscitation staff and access to an emergency room are immediately available.

Basal serum tryptase as risk assessment for severe Hymenoptera sting reactions in elderly.

BACKGROUND: Epidemiologic studies suggest that elderly people are more prone to develop severe anaphylactic reactions. However, the exact cause for this phenomenon remains unclear. AIMS OF THE STUDY: To study the role of the serum tryptase as a diagnostic parameter for individual risk evaluation and its impact on the severity of allergic reactions in elderly people. METHODS: Two hundred and seventy-four consecutive patients visiting the Department of Dermatology, Tübingen, Germany, who were diagnosed with honeybee or wasp venom allergy, were included in the study. RESULTS: Sting reaction severity increased with increased age and tryptase levels (P = 0.001 and P = 0.0003, respectively). Furthermore, we find not only a general increment in tryptase levels in elderly people (P = 0.0001) but also a continuous increase in tryptase concentrations even below the cut-off (11.4 microg/l) with increasing age (P = 0.0026). CONCLUSIONS: Our data confirm serum tryptase as a risk factor for severe anaphylactic reaction to hymenoptera stings. Furthermore, we give first evidence that basal serum tryptase levels increase continuously with age and being an indicator for either increased mast cell load or reactivity this can at least partly be responsible for the observed aggravated allergic reactions in elderly people. As those patients are at increased risk for life-threatening anaphylactic reactions, it should be considered to adjust VIT especially in elderly patients with elevated tryptase levels as recommended for patients with mastocytosis by increasing venom doses during VIT and by considering its life-long continuation.

[Medical and biological safety assessment of genetically modified maize event MIR604].

There are presented the results of genotoxicologic, immunologic and allergologic examinations which were conducted within the framework of integrated medical and biological assessment of genetically modified rootworm Diabrotica spp.-protected maize event MIR604. Analysis of damages of DNA and structural chromosome aberrations, assessment of the allergenic potential and immunoreactive properties has not confirmed any genotoxic, allergenic and immunotoxic effect of maize event MIR604.