George Du Toit

Early consumption of peanuts in infancy is associated with a low prevalence of peanut allergy

BACKGROUND Despite guidelines recommending avoidance of peanuts during infancy in the United Kingdom (UK), Australia, and, until recently, North America, peanut allergy (PA) continues to increase in these countries. OBJECTIVE We sought to determine the prevalence of PA among Israeli and UK Jewish children and evaluate the relationship of PA to infant and maternal peanut consumption. METHODS A clinically validated questionnaire determined the prevalence of PA among Jewish schoolchildren (5171 in the UK and 5615 in Israel). A second validated questionnaire assessed peanut consumption and weaning in Jewish infants (77 in the UK and 99 in Israel). RESULTS The prevalence of PA in the UK was 1.85%, and the prevalence in Israel was 0.17% (P < .001). Despite accounting for atopy, the adjusted risk ratio for PA between countries was 9.8 (95% CI, 3.1-30.5) in primary school children. Peanut is introduced earlier and is eaten more frequently and in larger quantities in Israel than in the UK. The median monthly consumption of peanut in Israeli infants aged 8 to 14 months is 7.1 g of peanut protein, and it is 0 g in the UK (P < .001). The median number of times peanut is eaten per month was 8 in Israel and 0 in the UK (P < .0001). CONCLUSIONS We demonstrate that Jewish children in the UK have a prevalence of PA that is 10-fold higher than that of Jewish children in Israel. This difference is not accounted for by differences in atopy, social class, genetic background, or peanut allergenicity. Israeli infants consume peanut in high quantities in the first year of life, whereas UK infants avoid peanuts. These findings raise the question of whether early introduction of peanut during infancy, rather than avoidance, will prevent the development of PA.

Household peanut consumption as a risk factor for the development of peanut allergy

BACKGROUND Most children with peanut allergy (PA) react on first known oral exposure to peanut. Recent data suggest cutaneous exposure as a route of sensitization. OBJECTIVES This study aimed to establish the relevant route of peanut exposure in the development of allergy. METHODS Questionnaires were administered to children with PA and to high-risk controls (with egg allergy) and controls without allergy. Questionnaires were completed before subjects were aware of their PA status, avoiding recall bias. Questionnaires recorded maternal peanut consumption during pregnancy, breast-feeding, and the first year of life. Peanut consumption was determined among all household members, allowing quantification of environmental household exposure (household peanut). RESULTS Median weekly household peanut in the 133 PA cases was significantly elevated (18.8 g) compared with 150 controls without allergy (6.9 g) and 160 high-risk controls (1.9 g). There were no differences in infant peanut consumption between groups. Differences in maternal peanut consumption during pregnancy (and lactation) were significant but become nonsignificant after adjusting for household peanut. A dose-response relationship was observed between environmental (nonoral) peanut exposure and the development of PA, which was strongest for peanut butter. Early oral exposure to peanut in infants with high environmental peanut exposure may have had a protective effect against the development of PA. CONCLUSIONS High levels of environmental exposure to peanut during infancy appear to promote sensitization, whereas low levels may be protective in atopic children. No effect of maternal peanut consumption during pregnancy or lactation is observed, supporting the hypothesis that peanut sensitization occurs as a result of environmental exposure.

Effect of Avoidance on Peanut Allergy after Early Peanut Consumption

BACKGROUND In a randomized trial, the early introduction of peanuts in infants at high risk for allergy was shown to prevent peanut allergy. In this follow-up study, we investigated whether the rate of peanut allergy remained low after 12 months of peanut avoidance among participants who had consumed peanuts during the primary trial (peanut-consumption group), as compared with those who had avoided peanuts (peanut-avoidance group). METHODS At the end of the primary trial, we instructed all the participants to avoid peanuts for 12 months. The primary outcome was the percentage of participants with peanut allergy at the end of the 12-month period, when the participants were 72 months of age. RESULTS We enrolled 556 of 628 eligible participants (88.5%) from the primary trial; 550 participants (98.9%) had complete primary-outcome data. The rate of adherence to avoidance in the follow-up study was high (90.4% in the peanut-avoidance group and 69.3% in the peanut-consumption group). Peanut allergy at 72 months was significantly more prevalent among participants in the peanut-avoidance group than among those in the peanut-consumption group (18.6% [52 of 280 participants] vs. 4.8% [13 of 270], P<0.001). Three new cases of allergy developed in each group, but after 12 months of avoidance there was no significant increase in the prevalence of allergy among participants in the consumption group (3.6% [10 of 274 participants] at 60 months and 4.8% [13 of 270] at 72 months, P=0.25). Fewer participants in the peanut-consumption group than in the peanut-avoidance group had high levels of Ara h2 (a component of peanut protein)-specific IgE and peanut-specific IgE; in addition, participants in the peanut-consumption group continued to have a higher level of peanut-specific IgG4 and a higher peanut-specific IgG4:IgE ratio. CONCLUSIONS Among children at high risk for allergy in whom peanuts had been introduced in the first year of life and continued until 5 years of age, a 12-month period of peanut avoidance was not associated with an increase in the prevalence of peanut allergy. Longer-term effects are not known. (Funded by the National Institute of Allergy and Infectious Diseases and others; LEAP-On ClinicalTrials.gov number, NCT01366846.).

Consensus Communication on Early Peanut Introduction and the Prevention of Peanut Allergy in High-risk Infants

The purpose of this brief communication is to highlight emerging evidence to existing guidelines regarding potential benefits of supporting early, rather than delayed, peanut introduction during the period of complementary food introduction in infants. This document should be considered as interim guidance based on consensus among the following organizations: American Academy of Allergy, Asthma & Immunology; American Academy of Pediatrics; American College of Allergy, Asthma & Immunology; Australasian Society of Clinical Immunology and Allergy; Canadian Society of Allergy and Clinical Immunology; European Academy of Allergy and Clinical Immunology; Israel Association of Allergy and Clinical Immunology; Japanese Society for Allergology; Society for Pediatric Dermatology; and World Allergy Organization. More formal guidelines regarding early-life, complementary feeding practices and the risk of allergy development will follow in the next year from the National Institute of Allergy and Infectious Diseases – sponsored Working Group and the European Academy of Allergy and Clinical Immunology.

Food‐dependent exercise‐induced anaphylaxis in childhood

The clinical syndrome of food‐dependent exercise‐induced anaphylaxis (FDEIA) is typified by the onset of anaphylaxis during (or soon after) exercise which was preceded by the ingestion of the causal food allergen/s. In FDEIA, both the food allergen/s and exercise are independently tolerated. FDEIA is an uncommon allergic condition in childhood, but nonetheless is an important differential diagnosis to be considered when faced by a child who has experienced exercise‐associated anaphylaxis. The diagnosis of FDEIA is heavily dependent on the clinical history. Allergy tests may need to be performed to a broad panel of food and food additives. Modified exercise challenges (performed with and without prior ingestion of food) are frequently required as allergy test results frequently return low‐positive results. A diagnosis of FDEIA facilitates the safe independent return to exercise and reintroduction of foods for patients who otherwise may unnecessarily avoid exercise and/or restrict their diet. The natural history of FDEIA is unknown; however, a safe return is usually achieved when the ingestion of the causal food allergen/s and exercise are separated.

International Consensus on Allergen Immunotherapy II: Mechanisms, standardization, and pharmacoeconomics

This article continues the comprehensive international consensus (ICON) statement on allergen immunotherapy (AIT). The initial article also recently appeared in the Journal. The conclusions below focus on key mechanisms of AIT-triggered tolerance, requirements in allergen standardization, AIT cost-effectiveness, and regulatory guidance. Potential barriers to and facilitators of the use of AIT are described in addition to future directions. International allergy specialists representing the European Academy of Allergy and Clinical Immunology; the American Academy of Allergy, Asthma & Immunology; the American College of Allergy, Asthma and Immunology; and the World Allergy Organization critically reviewed the existing literature and prepared this summary of recommendations for best AIT practice. The authors contributed equally and reached consensus on the statements presented herein.

Distinct parameters of the basophil activation test reflect the severity and threshold of allergic reactions to peanut

Background The management of peanut allergy relies on allergen avoidance and epinephrine autoinjector for rescue treatment in patients at risk of anaphylaxis. Biomarkers of severity and threshold of allergic reactions to peanut could significantly improve the care for patients with peanut allergy. Objective We sought to assess the utility of the basophil activation test (BAT) to predict the severity and threshold of reactivity to peanut during oral food challenges (OFCs). Methods The severity of the allergic reaction and the threshold dose during OFCs to peanut were determined. Skin prick tests, measurements of specific IgE to peanut and its components, and BATs to peanut were performed on the day of the challenge. Results Of the 124 children submitted to OFCs to peanut, 52 (median age, 5 years) reacted with clinical symptoms that ranged from mild oral symptoms to anaphylaxis. Severe reactions occurred in 41% of cases, and 57% reacted to 0.1 g or less of peanut protein. The ratio of the percentage of CD63+ basophils after stimulation with peanut and after stimulation with anti-IgE (CD63 peanut/anti-IgE) was independently associated with severity (P = .001), whereas the basophil allergen threshold sensitivity CD-sens (1/EC50 × 100, where EC50 is half maximal effective concentration) value was independently associated with the threshold (P = .020) of allergic reactions to peanut during OFCs. Patients with CD63 peanut/anti-IgE levels of 1.3 or greater had an increased risk of severe reactions (relative risk, 3.4; 95% CI, 1.8-6.2). Patients with a CD-sens value of 84 or greater had an increased risk of reacting to 0.1 g or less of peanut protein (relative risk, 1.9; 95% CI, 1.3-2.8). Conclusions Basophil reactivity is associated with severity and basophil sensitivity is associated with the threshold of allergic reactions to peanut. CD63 peanut/anti-IgE and CD-sens values can be used to estimate the severity and threshold of allergic reactions during OFCs.

Peanut protein in household dust is related to household peanut consumption and is biologically active

BACKGROUND Peanut allergy is an important public health concern. To understand the pathogenesis of peanut allergy, we need to determine the route by which children become sensitized. A dose-response between household peanut consumption (HPC; used as an indirect marker of environmental peanut exposure) and the development of peanut allergy has been observed; however, environmental peanut exposure was not directly quantified. OBJECTIVE We sought to explore the relationship between reported HPC and peanut protein levels in an infants home environment and to determine the biological activity of environmental peanut. METHODS Peanut protein was quantified in wipe and dust samples collected from 45 homes with infants by using a polyclonal peanut ELISA. Environmental peanut protein levels were compared with peanut consumption assessed by using a validated peanut food frequency questionnaire and other clinical and household factors. Biological activity of peanut protein in dust was assessed with a basophil activation assay. RESULTS There was a positive correlation between peanut protein levels in the infants bed, crib rail, and play area and reported HPC over 1 and 6 months. On multivariate regression analysis, HPC was the most important variable associated with peanut protein levels in the infants bed sheet and play area. Dust samples containing high peanut protein levels induced dose-dependent activation of basophils in children with peanut allergy. CONCLUSIONS We have shown that an infants environmental exposure to peanut is most likely to be due to HPC. Peanut protein in dust is biologically active and should be assessed as a route of possible early peanut sensitization in infants.

Reviews and feature articleConsensus communication on early peanut introduction and the prevention of peanut allergy in high-risk infants

The purpose of this brief communication is to highlight emerging evidence to existing guidelines regarding potential benefits of supporting early, rather than delayed, peanut introduction during the period of complementary food introduction in infants. This document should be considered as interim guidance based on consensus among the following organizations: American Academy of Allergy, Asthma & Immunology, American Academy of Pediatrics, American College of Allergy, Asthma & Immunology, Australasian Society of Clinical Immunology and Allergy, Canadian Society of Allergy and Clinical Immunology, European Academy of Allergy and Clinical Immunology, Israel Association of Allergy and Clinical Immunology, Japanese Society for Allergology, Society for Pediatric Dermatology, and World Allergy Organization. More formal guidelines regarding early-life, complementary feeding practices and the risk of allergy development will follow in the next year from the National Institute of Allergy and Infectious Diseases-sponsored Working Group and the European Academy of Allergy and Clinical Immunology.

Allergen immunotherapy for IgE-mediated food allergy: a systematic review and meta-analysis.

The European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines for Allergen Immunotherapy (AIT) for IgE‐mediated Food Allergy. To inform the development of clinical recommendations, we sought to critically assess evidence on the effectiveness, safety and cost‐effectiveness of AIT in the management of food allergy.