Clinical features of acute allergic reactions to peanut and tree nuts in children

Background. Peanut (PN) and tree nut (TN) allergies are potentially life-threatening, rarely outgrown, and appear to be increasing in prevalence. However, there is relatively little reported about the clinical features of acute reactions to these foods and their potential association. Objective. To describe the clinical features of acute reactions during initial and subsequent accidental ingestions of PN and TN among children with a history of at least one acute allergic reaction to these foods. Design. Questionnaire survey, examination, and serologic testing for specific IgE antibody of patients with convincing histories of acute reactions (at least one organ system involved within 60 minutes of ingestion) to PN or TN. Results. A total of 122 patients (63% males; median age, 8 years at time of study) had acute reactions; 68 had reactions only to PN, 20 only to TN, and 34 to both PN and TN. Of those reacting to TN, 34 had reactions to one, 12 to two, and 8 to three or more different TN, the most common being walnut, almond, and pecan. Initial reactions usually occurred at home (median age, 24 months for PN and 62 months for TN) and were considered to result from a first exposure in 72% of cases. Eighty-nine percent of the reactions involved the skin (urticaria, angioedema), 52% the respiratory tract (wheezing, throat tightness, repetitive coughing, dyspnea), and 32% the gastrointestinal tract (vomiting, diarrhea). Two organ systems were affected in 31% of initial reactions, and all three in 21% of reactions. Thirty-eight of 190 first reactions to PN or TN were treated with epinephrine. Accidental ingestions occurred in 55% of PN-allergic children (average of two accidents per patient with an accidental ingestion) and in 30% of TN-allergic children over a median period of 5.5 years. On average, symptoms after accidental exposure were generally similar to those at initial exposure. Accidents occurred commonly in school but also at home and in restaurants. Modes of accidental ingestion included sharing food, hidden ingredients, cross-contamination, and school craft projects using peanut butter. Eighty-three percent of the children were breastfed, with >90% of the mothers ingesting PN and at least one TN during lactation. Among patients reporting no history of exposure (>60% of patients for each TN), IgE antibodies were found to a particular TN in 50% to 82% of patients and to PN in 100% of patients. Conclusions. Acute allergic reactions to PN occur early in life. PN and TN allergic reactions coexist in one third of PN-allergic patients, frequently occur on first known exposure, and may be life-threatening, requiring emergency treatment. Accidental ingestions are common, occur frequently outside of the home, and often require emergency treatment. Consequently, early diagnosis followed by education on avoidance and treatment measures (including self-administered epinephrine) is imperative

Allergenicity assessment of genetically modified crops—what makes sense?

GM crops have great potential to improve food quality, increase harvest yields and decrease dependency on certain chemical pesticides. Before entering the market their safety needs to be scrutinized. This includes a detailed analysis of allergenic risks, as the safety of allergic consumers has high priority. However, not all tests currently being applied to assessing allergenicity have a sound scientific basis. Recent events with transgenic crops reveal the fallacy of applying such tests to GM crops

Prevalence of peanut and tree nut allergy in the US determined by a random digit dial telephone survey

Background: Allergy to peanuts and tree nuts (TNs) is one of the leading causes of fatal and near-fatal food-induced allergic reactions. These allergies can be lifelong and appear to be increasing in prevalence. Despite the seriousness of these allergies, the prevalence of peanut and TN allergy in the general population is unknown. Objective: We sought to determine the prevalence of peanut and TN allergy among the general population of the United States. Methods: We used a nationwide, cross-sectional, random digit dial telephone survey with a standardized questionnaire. Results: A total of 4374 households contacted by telephone participated (participation rate, 67%), representing 12,032 individuals. Peanut or TN allergy was self-reported in 164 individuals (1.4%; 95% confidence interval [CI], 1.2%-1.6%) in 151 households (3.5%; 95% CI, 2.9%-4.0%). The prevalence of reported allergy in adults (1.6%) was higher than that found in children under 18 years of age (0.6%). In 131 individuals, details of the reactions were obtained. When applying criteria requiring reactions to be typical of IgE-mediated reactions (hives, angioedema, wheezing, throat tightness, vomiting, and diarrhea) within an hour of ingestion, 10% of these subjects were excluded. Among the remaining 118 subjects, allergic reactions involved 1 organ system (skin, respiratory, or gastrointestinal systems) in 50 subjects, 2 in 45 subjects, and all 3 in 23 subjects. Forty-five percent of these 118 respondents reported more than 5 lifetime reactions. Only 53% of these 118 subjects ever saw a physician for the allergic reaction, and only 7% had self-injectable epinephrine available at the time of the interview. The prevalence of peanut and TN allergy was adjusted by assuming that 10% of the remaining 33 subjects without a description of their reactions would also be excluded and correcting for a 7% false-positive rate for the survey instrument. A final “corrected” prevalence estimate of 1.1% (95% CI, 1.0%-1.4%) was obtained. Conclusions: Peanut and/or TN allergy affects approximately 1.1% of the general population, or about 3 million Americans, representing a significant health concern. Despite the severity of reactions, about half of the subjects never sought an evaluation by a physician, and only a few had epinephrine available for emergency use

Skin exposure promotes a Th2-dependent sensitization to peanut allergens

Sensitization to foods often occurs in infancy, without a known prior oral exposure, suggesting that alternative exposure routes contribute to food allergy. Here, we tested the hypothesis that peanut proteins activate innate immune pathways in the skin that promote sensitization. We exposed mice to peanut protein extract on undamaged areas of skin and observed that repeated topical exposure to peanut allergens led to sensitization and anaphylaxis upon rechallenge. In mice, this epicutaneous peanut exposure induced sensitization to the peanut components Ara h 1 and Ara h 2, which is also observed in human peanut allergy. Both crude peanut extract and Ara h 2 alone served as adjuvants, as both induced a bystander sensitization that was similar to that induced by the atopic dermatitisassociated staphylococcal enterotoxin B. In cultured human keratinocytes and in murine skin, peanut extract directly induced cytokine expression. Moreover, topical peanut extract application induced an alteration dependent on the IL-33 receptor ST2 in skin-draining DCs, resulting in Th2 cytokine production from T cells. Together, our data support the hypothesis that peanuts are allergenic due to inherent adjuvant activity and suggest that skin exposure to food allergens contributes to sensitization to foods in early life.The work was supported by NIH grants AI044236 (to H.A. Sampson and M.C. Berin), AI093577 (to M.C. Berin), and AI091655 (to K.M. Järvinen) and Environmental Protection Agency grant R834064 (to M.C. Berin). Clinical specimens were provided by the Jaffe Food Allergy Resource Initiative, funded by Food Allergy Research and Education.Peer Reviewe

Skin exposure promotes a Th2-dependent sensitization to peanut allergens

Sensitization to foods often occurs in infancy, without a known prior oral exposure, suggesting that alternative exposure routes contribute to food allergy. Here, we tested the hypothesis that peanut proteins activate innate immune pathways in the skin that promote sensitization. We exposed mice to peanut protein extract on undamaged areas of skin and observed that repeated topical exposure to peanut allergens led to sensitization and anaphylaxis upon rechallenge. In mice, this epicutaneous peanut exposure induced sensitization to the peanut components Ara h 1 and Ara h 2, which is also observed in human peanut allergy. Both crude peanut extract and Ara h 2 alone served as adjuvants, as both induced a bystander sensitization that was similar to that induced by the a topic dermatitis associated staphylococcal enterotoxin B. In cultured human keratinocytes and in murine skin, peanut extract directly induced cytokine expression. Moreover, topical peanut extract application induced an alteration dependent on the IL-33 receptor ST2 in skin-draining DCs, resulting in Th2 cytokine production from T cells. Together, our data support the hypothesis that peanuts are allergenic due to inherent adjuvant activity and suggest that skin exposure to food allergens contributes to sensitization to foods in early life

The natural history of peanut allergy

Background: It has traditionally been assumed that peanut allergy is rarely outgrown. Objective: The goal of this study was to determine the number of children with peanut allergy who become tolerant of peanut. Methods: Patients aged 4 to 20 years with a diagnosis of peanut allergy were evaluated by questionnaire, skin testing, and a quantitative antibody fluorescent-enzyme immunoassay. Patients who had been reaction free in the past year and had a peanut IgE (PN-IgE) level less than 20 kilounits of antibody per liter (kUA/L) were offered an open or double-blind, placebo-controlled peanut challenge. Results: A total of 223 patients were evaluated, and of those, 85 (PN-IgE less than 0.35-20.4 kUA/L [median 1.42 kUA/L]) participated in an oral peanut challenge. Forty-eight (21.5%) patients had negative challenge results and were believed to have outgrown their peanut allergy (aged 4-17.5 years [median 6 years]; PN-IgE less than 0.35-20.4 kUA/L [median 0.69 kUA/L]). Thirty-seven failed the challenge (aged 4-13 years [median 6.5 years]; RAST less than 0.35-18.2 kUA/L [median 2.06 kUA/L]). Forty-one patients with PN-IgE levels less than 20 kUA/L declined to undergo challenge, and 97 were not eligible for challenge because their PN-IgE levels were greater than 20 kUA/L or they had had a recent reaction. Sixty-seven percent of patients with PN-IgE levels less than 2 kUA/L and 61% with levels less than 5 kUA/L had negative challenge results. Of those who underwent challenge, PN-IgE levels for those who passed versus those who failed were different at the time of challenge (P = .009), but not at the time of diagnosis (P = .25). Conclusion: This study demonstrates that peanut allergy is outgrown in about 21.5% of patients. Patients with low PN-IgE levels should be offered a peanut challenge in a medical setting to demonstrate whether they can now tolerate peanuts

Standardization and performance evaluation of mononuclear cell cytokine secretion assays in a multicenter study

BACKGROUND: Cryopreservation of peripheral blood mononuclear cells has been used to preserve and standardize immunologic measurements for multicenter studies, however, effects of cryopreservation on cytokine responses are incompletely understood. In designing immunologic studies for a new multicenter birth cohort study of childhood asthma, we performed a series of experiments to determine the effects of two different methods of cryopreservation on the cytokine responses of cord and peripheral blood mononuclear cells. RESULTS: Paired samples of PBMC were processed freshly, or after cryopreservation in a Nalgene container (NC) or a controlled-rate freezer (CRF). Although there were some differences between the methods, cryopreservation inhibited PHA-induced IL-10 secretion and Der f 1-induced IL-2 secretion, and augmented PHA-induced IL-2 secretion and spontaneous secretion of TNF-α. In separate experiments, NC cryopreservation inhibited secretion of several cytokines (IL-13, IL-10, IFN-γ, TNF-α) by PHA-stimulated cord blood mononuclear cells. With the exception of PHA-induced IL-13, results from fresh and cryopreserved cord blood samples were not significantly correlated. Finally, in reproducibility studies involving processing of identical cell samples in up to 4 separate laboratories, variances in cytokine responses of fresh cells stimulated at separate sites did not exceed those in cryopreserved cells stimulated at a central site. CONCLUSION: Collectively, these studies indicate that cryopreservation can affect mononuclear cell cytokine response profiles, and that IL-10 secretion and antigen-induced responses may be especially vulnerable. These studies also demonstrate that mononuclear cell responses can be standardized for performance in a small number of laboratories for multicenter studies, and underscore the importance of measuring reproducibility and of testing whether cryopreservation techniques alter specific immunologic outcomes

Improvements in quality of life in children following epicutaneous immunotherapy (EPIT) for peanut allergy in the PEPITES and PEOPLE studies

Background: Food allergy quality of life (FAQL) is impaired in children with peanut allergy. Food Allergy Quality of Life Questionnaires (FAQLQs) provide disease-specific insight into the burden of peanut allergy and potential FAQL changes after peanut immunotherapy. Objective: To examine FAQL changes in children after treatment with epicutaneous immunotherapy for peanut allergy (250 μg, daily epicutaneous peanut protein; DBV712 250 μg). Methods: FAQL was prospectively measured using the FAQLQ parent proxy form (Food Allergy Quality of Life Questionnaire-Parent Proxy Form [FAQLQ-PF], for children aged ≤12 years) and child form (Food Allergy Quality of Life Questionnaire-Child Form [FAQLQ-CF], child rated if aged ≥8 years) during the 12-month double-blind, randomized, controlled Peanut EPIT Efficacy and Safety Study (PEPITES) trial and the initial 12 months of the open-label PEPITES Open Label Extension Study (PEOPLE) follow-up study. Data were analyzed for between-group differences after treatment unblinding. Results: FAQLQs from placebo participants (FAQLQ-PF: 96; FAQLQ-CF: 47) and treatment group participants (FAQLQ-PF: 209; FAQLQ-CF: 105) were analyzed. Twenty-four–month global FAQL scores (FAQLQ-PF/FAQLQ-CF) were significantly improved in the treatment group versus the placebo group (least squares mean, 0.34, P = .008, and 0.46, P = .023, respectively). At 24 months, there was significant FAQLQ-PF score improvement in participants initially randomized to treatment who met the efficacy primary end point (n = 74; least squares mean, 0.55; P < .001) and in participants with any eliciting dose increase (n = 127; least squares mean, 0.66; P < .001). FAQLQ-PF improvements were observed in social dietary limitations (P = .002), food-related anxiety (P = .029), and emotional impact (P = .048) domains. FAQLQ-CF improvements were observed in risk of accidental exposure (P = .002) and allergen avoidance (P = .04) domains. Nearly all outcomes met a nontreatment context minimal clinically important difference previously cited for FAQLQ. Conclusions: Epicutaneous immunotherapy treatment was observed to be associated with significant global and domain-specific FAQL improvement (FAQLQ-PF/FAQLQ-CF), largely driven by increases in eliciting dose, in children with peanut allergy