To the Editor,

Background Due to changes in dietary habits tree nuts (TN) are consumed in many households and TN allergy appears to be increasing. One risk factor seems to be allergies to other food such as peanuts. The aim of our study was to investigate, how often peanut-sensitized infants and toddlers are co-sensitized to cashew, hazelnut and walnut and to determine the likelihood of its clinical relevance by their 2S albumin-specific (s)IgE. Methods Sera of 101 peanut-sensitized children, 5 to 24 months of age (median 16 months) were analyzed regarding sIgE to hazelnut, walnut and cashew and to their 2S-albumins Cor a 14, Jug r 1 and Ana o 3 as well as to Ara h 1 and 2, by using the NOVEOS TM immunoanalyzer system. Results 96% of the peanut-sensitized children were co-sensitized to at least one TN with 94.1% to hazelnut, 87.1% to walnut and 84.2% to cashew. More than half (58.4%) of the children were sensitized to at least one 2S albumin with similar rates for infants and toddlers, 26.7% to all three. Moreover, sensitization rates were similar in peanut allergic and tolerant children. Estimating the likelihood of clinical relevance, 15.8% of all peanut-sensitized children had an at least 90% probability to be hazelnut and/or cashew allergic. Conclusion TN sensitization seems to be common among peanut-sensitized infants and toddlers. Many had a high likelihood to be TN allergic. Therefore, it should be considered to determine TN-sIgE in peanut-sensitized children if TN are not consumed so far.

Background: In order to determine tolerance development in hen’s egg (HE) allergic children, international guidelines recommend an oral food challenge after 6-24 months. This study aimed to assess whether parents follow this advice and factors that influence their decision. Methods: A follow-up of 158 challenge-proven HE allergic children was performed. Families who did not come to a rechallenge were contacted by phone and a standardized survey relating to the current allergy status was conducted. Logistic regression models were used to assess the effect of clinical and laboratory characteristics on the reevaluation of the allergy status. Results: 35% of the HE-allergic children conducted a rechallenge in a hospital, 27% continued avoiding HE without reevaluation and 11% performed a “home-testing” with HE. The odds ratio for patients to test for HE tolerance at home instead of in a hospital increased 7.94 times (CI:2.31-27.31) for every decrease in the severity score at the initial challenge, and 3.24 times (CI:1.26-8.33) for every decrease of the baseline specific IgE CAP-class. Tolerance of heated HE prior to reevaluation was most frequent in the home-tested (100%) and was more frequent in patients, who continued avoidance (68%) compared to those, who were rechallenged (44%). Conclusions: Our data suggest an association between reaction severity as well as specific IgE levels at initial food challenge and the choice of families whether and how to evaluate natural tolerance development in their HE-allergic child. Individualized management may be needed in order to achieve safe and effective medical care for these patients.

Background There is substantial interest in allergen-specific immunotherapy in food allergy. We systematically reviewed its efficacy and safety. Methods We searched six bibliographic databases from 1946 to 30 April 2021 for randomised controlled trials about immunotherapy alone or with biologicals in IgE-mediated food allergy confirmed by oral food challenge. We pooled the data using random-effects meta-analysis. Results We included 36 trials with 2,126 participants, mainly children. Oral immunotherapy increased tolerance whilst on therapy for peanut (RR 9.9, 95% CI 4.5. to 21.4, high certainty); cow’s milk (RR 5.7, 1.9 to 16.7, moderate certainty) and hen’s egg allergy (RR 8.9, 4.4 to 18, moderate certainty). The number needed to treat to increase tolerance to a single dose of 300mg or 1000mg peanut protein was 2. In peanut allergy, oral immunotherapy did not increase adverse reactions (RR 1.1, 1.0 to 1.2, low certainty) or severe reactions (RR 1,6, 0.7 to 3.5, low certainty). It may increase adverse reactions in cow’s milk (RR 3.9, 2.1 to 7.5, low certainty) and hen’s egg allergy (RR 7.0, 2.4 to 19.8, moderate certainty), but reactions tended to be mild and gastrointestinal. Epicutaneous immunotherapy increased tolerance whilst on therapy for peanut (RR 2.6, 1.8 to 3.8, moderate certainty). Results were unclear for other allergies and administration routes. Conclusions Oral immunotherapy improves tolerance whilst on therapy and is probably safe in peanut, cow’s milk and hen’s egg allergy. However, our review found little about whether this improves quality of life, is sustained or cost-effective.

A document by Jana Eckert. Click on the document to view its contents.

Background: Allergic diseases are the most prevalent chronic childhood diseases resulting in a massive societal and economic burden for the community and a significant reduction of health-related quality of life (HRQoL) for affected families. The project CHAMP (CHildhood Allergy and tolerance: bioMarkers and Predictors) was funded in 2017 by the German Federal Ministry for Education and Research. Methods: CHAMP investigates the determinants of different allergic diseases from birth to adolescence to identify clinically relevant biomarkers predicting onset, progression, remission and severity. Data on HRQoL and patient’s needs and requirements were collected, supported by the German Asthma and Allergy Association (DAAB). Using validated questionnaires and outpatient visits, eight subprojects analysed allergic diseases in epidemiological or clinical cohorts (more than 2500 children/adolescents), sampling numerous biomaterials to assess omics on several levels. Murine models disentangled underlying mechanisms of early tolerance, translating findings from the cohorts to models and vice versa. Results: The DAAB survey, including 851 participants, showed that 83% were interested in prediction of the course of different current allergic diseases and future manifestation. 86% of participants considered doctor’s specialized training and their education as highly important, over 70% chose research for allergy understanding and prevention as critical. CHAMP addresses these needs. Common SOPs have been established and recruitment is ongoing. Conclusion: The DAAB patient survey confirmed the critical need for translational allergy research. CHAMP envisions to predict onset, tolerance and remission of allergic diseases and to identify disease sub-phenotypes for future development of preventive strategies and novel avenues for therapeutic options.

Background This systematic review used the GRADE approach to compile evidence to inform an anaphylaxis guideline from the European Academy of Allergy and Clinical Immunology (EAACI). Methods We searched five bibliographic databases from 1946 to 20 April 2020 for studies about the diagnosis, management and prevention of anaphylaxis. We included 50 studies with 18,449 participants: 29 randomised controlled trials, seven controlled clinical trials, seven consecutive case series and seven case-control studies. Findings were summarised narratively because studies were too heterogeneous to conduct meta-analysis. Results It is unclear whether the NIAID/FAAN criteria or Brighton case definition are valid for immediately diagnosing anaphylaxis due to the very low certainty of evidence. Adrenaline is the cornerstone of first-line emergency management of anaphylaxis but, due to ethical constraints, little robust research has assessed its effectiveness . Newer models of adrenaline autoinjectors may slightly increase the proportion of people correctly using the devices and reduce time to administration. Face-to-face training for laypeople may slightly improve anaphylaxis knowledge and competence in using autoinjectors. Adrenaline prophylaxis prior to snake bite anti-venom may reduce anaphylaxis but the impact of prophylactic corticosteroids and antihistamines is uncertain. There was insufficient evidence about the impact of other anaphylaxis management strategies. Conclusions Anaphylaxis is a potentially life-threatening condition but, due to practical and ethical challenges, there is a paucity of robust evidence about how to diagnose and manage it.