Risk Factors for Anaphylaxis in Children Allergic to Peanuts.

Background and Objectives: A peanut allergy is the most common single cause of anaphylaxis in children. The risk factors for anaphylaxis in children with a peanut allergy are not well defined. Therefore, we aimed to identify epidemiological, clinical, and laboratory characteristics of children with a peanut allergy that may predict the severity of the allergic reaction and anaphylaxis. Materials and Methods: We conducted a cross-sectional study and included 94 children with a peanut allergy. Allergy testing was performed, including skin prick testing and the determination of specific IgE levels to peanuts and their Ara h2 component. In case of discordance between patient history and allergy testing, an oral food challenge with peanuts was performed. Results: Anaphylaxis and moderate and mild reactions to peanuts occurred in 33 (35.1%), 30 (31.9%), and 31 (33.0%) patients, respectively. The severity of the allergic reaction was only weakly correlated (p = 0.04) with the amount of peanuts consumed. The median number of allergic reactions to peanuts was 2 in children with anaphylaxis compared to 1 in other patients (p = 0.04). The median level of specific IgE to Ara h2 was 5.3 IU/mL in children with anaphylaxis compared to 0.6 IU/mL and 10.3 IU/mL in children with mild and moderate peanut allergies (p = 0.06). The optimal cutoff for distinguishing between anaphylaxis and a less severe allergic reaction to peanuts was a specific IgE Ara h2 level of 0.92 IU/mL with 90% sensitivity and 47.5% specificity for predicting anaphylaxis (p = 0.04). Conclusions: Epidemiological and clinical characteristics of the patient cannot predict the severity of the allergic reaction to peanuts in children. Even standard allergy testing, including component diagnostics, is a relatively poor predictor of the severity of an allergic reaction to peanuts. Therefore, more accurate predictive models, including new diagnostic tools, are needed to reduce the need for oral food challenge in most patients.

Reactions to peanut at first introduction in infancy are associated with age ≥8 months and severity of eczema.

BACKGROUND: Previous studies have shown the efficacy of the early introduction of peanut to prevent peanut allergy. Due to the exclusion of infants with sensitization to peanut, it remains unclear what the optimal timing of introduction is. METHODS: The PeanutNL study was performed in 6 pediatric allergology centers in the Netherlands. Infants referred for the clinical early introduction of peanut to prevent peanut allergy underwent skin prick tests for peanut and an oral peanut challenge at a median age of 6 months. RESULTS: One hundred sixty two of 707 infants (23%) who had never eaten peanut before were sensitized to peanut, of which 80 (49%) had wheals of >4 mm. Sixty seven of 707 infants (9.5%) had a positive oral challenge to peanut at first introduction. Multivariate analysis revealed that age (p < .001) and SCORAD eczema severity scores (p = .001) were significant risk factors. Introduction of peanut at ≥8 months in infants with moderate and severe eczema resulted in an increased risk (odds ratio 5.24 (p = .013) and 3.61 (p = .019), respectively) of having reactions to peanut as compared to introduction before 8 months. A family history of peanut allergy and previous reactions to egg were not identified as independent risk factors. CONCLUSION: These results suggest that peanut should be introduced before the age of 8 months to reduce the risk of reactions at first exposure in infants with moderate and severe eczema. Furthermore, since children with severe eczema have the highest risk of reactions, the clinical introduction of peanut should be considered, at the latest at the age of 7 months.

Phase 3 Trial of Epicutaneous Immunotherapy in Toddlers with Peanut Allergy.

BACKGROUND: No approved treatment for peanut allergy exists for children younger than 4 years of age, and the efficacy and safety of epicutaneous immunotherapy with a peanut patch in toddlers with peanut allergy are unknown. METHODS: We conducted this phase 3, multicenter, double-blind, randomized, placebo-controlled trial involving children 1 to 3 years of age with peanut allergy confirmed by a double-blind, placebo-controlled food challenge. Patients who had an eliciting dose (the dose necessary to elicit an allergic reaction) of 300 mg or less of peanut protein were assigned in a 2:1 ratio to receive epicutaneous immunotherapy delivered by means of a peanut patch (intervention group) or to receive placebo administered daily for 12 months. The primary end point was a treatment response as measured by the eliciting dose of peanut protein at 12 months. Safety was assessed according to the occurrence of adverse events during the use of the peanut patch or placebo. RESULTS: Of the 362 patients who underwent randomization, 84.8% completed the trial. The primary efficacy end point result was observed in 67.0% of children in the intervention group as compared with 33.5% of those in the placebo group (risk difference, 33.4 percentage points; 95% confidence interval, 22.4 to 44.5; P<0.001). Adverse events that occurred during the use of the intervention or placebo, irrespective of relatedness, were observed in 100% of the patients in the intervention group and 99.2% in the placebo group. Serious adverse events occurred in 8.6% of the patients in the intervention group and 2.5% of those in the placebo group; anaphylaxis occurred in 7.8% and 3.4%, respectively. Serious treatment-related adverse events occurred in 0.4% of patients in the intervention group and none in the placebo group. Treatment-related anaphylaxis occurred in 1.6% in the intervention group and none in the placebo group. CONCLUSIONS: In this trial involving children 1 to 3 years of age with peanut allergy, epicutaneous immunotherapy for 12 months was superior to placebo in desensitizing children to peanuts and increasing the peanut dose that triggered allergic symptoms. (Funded by DBV Technologies; EPITOPE ClinicalTrials.gov number, NCT03211247.).

Doing More with Less.

Peanut allergy affects 1 to 3% of children in Western countries and is increasing in prevalence in Africa and Asia. In most patients, peanut allergy develops early in life and continues into adulthood. Peanut allergy is the most common cause of food-related anaphylaxis and death and creates significant medical, financial, and psychosocial burdens on patients and their families.1-3 Until recently, the mainstay of treatment for peanut and other food allergies was strict avoidance of peanut and carrying injectable epinephrine in case of accidental exposure.

Early-life predictors and risk factors of peanut allergy, and its association with asthma in later-life: Population-based birth cohort study.

BACKGROUND: Understanding risk factors for peanut allergy (PA) is essential to develop effective preventive measures. OBJECTIVE: The objective was to ascertain associates and predictors of PA, and the relationship between PA and asthma severity. METHODS: In a population-based birth cohort, we investigated the association between objectively confirmed PA with early-life environmental exposures, filaggrin (FLG)-loss-of-function mutations and other atopic disease. We then examined the association of PA with longitudinal trajectories of sensitization, wheeze and allergic comorbidities, which were previously derived using machine learning. Finally, we ascertained the relationship between PA and asthma severity. RESULTS: PA was confirmed in 30/959 participants with evaluable data. In the multivariate analysis, eczema in infancy (OR = 4.4, 95% CI 1.5-13.2, p = 0.007), egg sensitization at age 3 years (OR = 9.7, 95% CI 3.3-29.9, p < 0.001) and early-life cat ownership (OR = 3.0, 95% CI 1.1-8.4, p = 0.04) were independent associates of PA. In the stratified analysis among 700 participants with genetic information, in children with early-life eczema there was no difference in FLG mutations between children with and without PA (3/18 [16.7%] vs. 42/220 [19.1%], p = 1.00). In contrast, among children without eczema, those with PA were almost eight times more likely to have FLG mutations (2/6 [33.3%] vs. 27/456 [5.9%], p = 0.049). We observed associations between PA and multiple allergic sensitization profiles derived using machine learning, with ~60-fold increase in risk among individuals assigned to multiple early sensitization. PA was significantly associated with persistent wheeze (but not other wheeze phenotypes), and with trajectories of atopic disease characterized by co-morbid persistent eczema and wheeze (but not with transient phenotypes). Children with PA were more likely to have asthma, but among asthmatics we found no evidence of an association between PA and asthma severity. CONCLUSIONS: Peanut allergy is associated with multiple IgE sensitization and early-onset persistent eczema and wheeze. FLG loss-of-function mutations were associated with peanut allergy in children without eczema.

Altered immune cell profiles and impaired CD4 T-cell activation in single and multi-food allergic adolescents.

BACKGROUND: Approximately 5% of adolescents have a food allergy, with peanut and tree nut allergies the most common. Having two or more food allergies in adolescence also doubles the risk of any adverse food reaction, and is associated with increased dietary and social burden. Investigations of immune function in persistently food allergic children are rare. OBJECTIVE: In the present study, we aimed to investigate the immune mechanisms that underlie food allergy in adolescence. METHODS: We used high-dimensional flow cytometry, unsupervised computational analysis and functional studies to comprehensively phenotype a range of non-antigen-specific immune parameters in a group of well-characterized adolescents with clinically defined single peanut allergy, multi-food allergy and aged-matched non-food allergic controls. RESULTS: We show that food allergic adolescents have higher circulating proportions of dendritic cells (p = .0084, FDR-adjusted p = .087, median in no FA: 0.63% live cells, in FA: 0.93%), and higher frequency of activated, memory-like Tregs relative to non-food allergic adolescents (p = .011, FDR-adjusted p = .087, median in no FA: 0.49% live cells, in FA: 0.65%). Cytokine profiling revealed that CD3/CD28 stimulated naïve CD4 T cells from food allergic adolescents produced less IL-6 (p = .0020, FDR-adjusted p = .018, median log2 fold change [stimulated/unstimulated] in no FA: 3.03, in FA: 1.92) and TNFα (p = .0044, FDR-adjusted p = .020, median in no FA: 9.16, in FA: 8.64) and may secrete less IFNγ (p = .035, FDR-adjusted p = .11, median in no FA: 6.29, in FA: 5.67) than naïve CD4 T cells from non-food allergic controls. No differences between clinical groups were observed for LPS-stimulated monocyte secretion of cytokines. CONCLUSIONS: These results have important implications for understanding the evolution of the immune response in food allergy throughout childhood, revealing that dendritic cell and T-cell signatures previously identified in early life may persist through to adolescence.

What Is Anaphylaxis? Pediatric Residents' Perception and Treatment of Anaphylactic Reactions.

To assess knowledge regarding symptoms and treatment of anaphylaxis, a vignette of a child having an allergic reaction to a peanut was presented to residents in an allergy clinic. Twelve sets of clinical outcomes ranging from severe multi-organ to mild single organ involvement were described, and residents were asked if each symptom set met criteria for diagnosis of anaphylaxis, whether epinephrine should be administered acutely and prescribed at follow-up, and whether peanuts should be avoided in the future. Of cases that met the definition of anaphylaxis 28.8% were incorrectly diagnosed, in 13.6% of cases they would allow peanuts to be eaten again, and in 23.9% of cases they would not prescribe epinephrine at follow-up. In 26.1% of cases meeting criteria for acute anaphylaxis residents would not administer epinephrine. Deficits regarding the diagnosis and treatment of anaphylaxis by residents were identified, and increased educational efforts are needed.

Food-induced anaphylaxis in infancy compared to preschool age: A retrospective analysis.

OBJECTIVE: Little is known regarding food anaphylaxis in infancy. We aimed to describe specificities of food anaphylaxis in infants (≤12 months) as compared to preschool children (1-6 years). METHODS: We conducted a retrospective study of all food anaphylaxis cases recorded by the Allergy Vigilance Network from 2002 to 2018, in preschool children focusing on infants. RESULTS: Of 1951 food anaphylaxis reactions, 61 (3%) occurred in infants and 386 (20%) in preschool children. Two infants had two anaphylaxis reactions; thus, we analyzed data among 59 infants (male: 51%; mean age: 6 months [SD: 2.9]); 31% had a history of atopic dermatitis, 11% of previous food allergy. The main food allergens were cow's milk (59%), hen's egg (20%), wheat (7%) and peanut (3%) in infants as compared with peanut (27%) and cashew (23%) in preschool children. Anaphylaxis occurred in 28/61 (46%) cases at the first cow's milk intake after breastfeeding discontinuation. Clinical manifestations were mainly mucocutaneous (79%), gastrointestinal (49%), respiratory (48%) and cardiovascular (21%); 25% of infants received adrenaline. Hives, hypotension and neurologic symptoms were more likely to be reported in infants than in preschool children (P = .02; P = .004; P = .002, respectively). Antihistamines and corticosteroids were more often prescribed in preschool children than in infants (P = .005; P = .025, respectively). CONCLUSION: Our study found that in infants presenting with their first food allergy, in a setting with a high rate of infant formula use, the most predominant trigger was cow's milk. As compared to older preschool children, hives, hypotonia and hypotension were more likely to be reported in infants. We believe that this represents a distinct food anaphylaxis phenotype that can further support developing the clinical anaphylaxis criteria in infants.

Current perspectives on peanut allergy.

Peanut allergy is increasingly prevalent and for most patients is a life-long condition, with the potential to cause life-threatening reactions. Accurate diagnosis and appropriate management are essential to minimise risks due to accidental peanut exposure. Current management strategies focus on strict allergen avoidance and access to emergency medicines to treat potential reactions; however, active approaches are an area of intense research. Promising new methods of food allergen immunotherapy are set to change the approach to managing peanut allergic patients in the near future.

Peanut allergy among Mexican adults with allergic respiratory diseases: prevalence and clinical manifestations.

BACKGROUND: Peanut allergy among adults with respiratory diseases has seldom been studied within Mexico. OBJECTIVE: To establish the prevalence of peanut allergy among adults that have been diagnosed with either asthma or allergic rhinitis; we will also be describing the symptoms that are associated with peanut allergy. METHODS: We carried out a cross-sectional study through which we analyzed the corresponding data of 257 patients with allergic respiratory diseases, asthma or allergic rhinitis, all participants were 16 years of age or older, and were recruited in a consecutive manner. Peanut allergy was established by testing positive to a peanut skin-prick test; we also conducted a standard interview with each patient. RESULTS: From our sample of 257 patients, 18 tested positive to peanut sensitization, (7.0%; 95% CI = 3.9% to 10.1%); among these 18 participants, 7 were considered to be allergic to peanuts (2.7%; 95% IC: 0.7% to 4.7%). Predominant symptoms were oral, primarily affecting the pharynx and the palate, followed by swelling of the lips. When it came to respiratory discomfort, sneezing and rhinorrhea stood out, and lastly there were cutaneous symptoms. We did not detect any systemic reactions to the peanut. CONCLUSION: In our study, peanut allergy among adults with allergic respiratory diseases is not an uncommon occurrence.

Antecedentes: La alergia al cacahuate en adultos con enfermedades respiratorias alérgicas pocas veces ha sido estudiada en México. Objetivo: Establecer la prevalencia de alergia al cacahuate en un grupo de adultos con asma o rinitis alérgica; también se describen los síntomas asociados con la alergia al cacahuate. Métodos: Se realizó estudio transversal en el que analizaron los datos correspondientes a 257 pacientes con enfermedades respiratorias alérgicas, asma o rinitis alérgica, con edad igual o mayor a 16 años; los pacientes fueron reclutados consecutivamente. La alergia al cacahuate se determinó por una prueba cutánea positiva al cacahuate y a través de una entrevista estandarizada. Se estimaron intervalos de confianza (IC) a 95 % para proporciones. Resultados: De los pacientes incluidos, 18 estuvieron sensibilizados al cacahuate (7.0 %, IC 95 % = 4.4-10.9), siete de ellos fueron considerados alérgicos al cacahuate, para una prevalencia de 2.7% (IC 95%: 1.2% - 5.6%). En los pacientes con alergia al cacahuate, los síntomas predominantes fueron los orales, principalmente el prurito en la faringe y en el paladar, seguidos de edema de los labios; entre las molestias respiratorias sobresalieron los estornudos y la rinorrea y, al final, los síntomas cutáneos. No se documentaron reacciones sistémicas al cacahuate. Conclusión: En nuestro estudio, la alergia al cacahuate en adultos con enfermedades respiratorias alérgicas no fue infrecuente.

Acquisition of tolerance to egg and peanut in African food-allergic children with atopic dermatitis.

BACKGROUND: There are no previous data on tolerance development in children with atopic dermatitis (AD) and concomitant food allergy in low- and middle-income settings. OBJECTIVES: To determine the rate of tolerance acquisition to egg and peanut 5 years after diagnosing food allergies in South African (SA) children with AD, and to explore factors influencing tolerance acquisition. METHODS: Five years after first diagnosing food allergy in 37 SA children with egg and/or peanut allergy, they were reassessed for their allergies by questionnaire, skin-prick tests (SPTs) and ImmunoCAP-specific IgE (sIgE) tests (Thermo Fisher Scientific/Phadia, Sweden) to egg white, ovomucoid, peanut and Arachis hypogaea allergen 2 (Ara h 2), and incremental food challenges. RESULTS: Eighteen of 25 originally egg-allergic patients and 19 of 24 originally peanut-allergic children were followed up at a median age of 8 years and 3 months and 9 years and 6 months, respectively. A high percentage of children (72.2%) outgrew their egg allergy, and 15.8% outgrew their peanut allergy. Allergic comorbidity remained high, with asthma increasing over time, and AD remaining moderate in severity in the cohort overall. At diagnosis, sIgE egg white ≤9.0 kU/L and sIgE ovomucoid ≤2.0 kU/L were associated with tolerance development to egg 5 years later. At follow-up, sIgE egg white ≤0.70 kU/L, sIgE ovomucoid ≤0.16 kU/L, SPT egg-white extract ≤1 mm and SPT fresh egg ≤5 mm were associated with tolerance. At diagnosis, sIgE Ara h 2 ≤1.7 kU/L and SPT peanut ≤10 mm were associated with tolerance development to peanut 5 years later. At follow-up, sIgE peanut ≤0.22 kU/L, sIgE Ara h 2 ≤0.18 kU/L and SPT peanut ≤5.5 mm were associated with tolerance. CONCLUSIONS: Egg allergy was outgrown in 72.2% and peanut allergy in 15.8% of SA children 5 years after diagnosis of AD. This is in keeping with findings derived from studies in higher socioeconomic settings, and can help to guide the counselling of patients with allergies to these foods of high nutritional value.

Propofol use in children with allergies to egg, peanut, soybean or other legumes.

Propofol is the most commonly administered intravenous agent for anaesthesia in children. However, there are concerns that the emulsified preparation may not be safe in children with an allergy to egg, peanut, soybean or other legumes. We conducted a retrospective study of children with immunologically confirmed egg, peanut, soybean or legume allergy and who underwent general anaesthesia at Princess Margaret Hospital for Children between 2005 and 2015. We extracted details regarding allergy diagnosis, each anaesthetic administered and any adverse events or signs of an allergic reaction in the peri-operative period. A convenience sample of patients without any known food allergies was identified from our prospective anaesthesia research database and acted as a control group. We identified 304 food-allergic children and 649 procedures where propofol was administered. Of these, 201 (66%) had an egg allergy, 226 (74%) had a peanut allergy, 28 (9%) had a soybean allergy and 12 (4%) had a legume allergy. These were compared with 892 allergy-free patients who were exposed to propofol. In 10 (3%) allergy patients and 124 (14%) allergy-free patients, criteria for a possible allergic reaction were met. In nine of the food-allergic children and in all the controls valid non-allergic explanations for the clinical symptoms were found. One likely mild allergic reaction was experienced by a child with a previous history of intralipid allergy. We conclude that genuine serious allergic reaction to propofol is rare and is not reliably predicted by a history of food allergy.

Managing Cross-Reactivity in Those with Peanut Allergy.

Peanut is an allergenic legume that can cross-react with other plant-based foods, notably other legumes and tree nuts. Peanut-allergic individuals can be both cosensitized and coallergic to such items, requiring foresight when eliciting a clinical history of a reaction, in the diagnostic evaluation of such allergies, and in the counseling of patients as to food avoidances after a diagnosis is made. Legume allergens belong to the Fabaceae family and encompass the cupin, prolamin, PR-10, and lipid transfer protein families, which mediate cross-sensitization including that between peanut and tree nut. Among legumes, the most common patterns of clinical cross-reactivity are between peanut and lupine, peanut and soy, as well as chickpea and lentil, though this is highly dependent on geography and prevalence of these foods in the diet. Issues of cross-sensitization may exist between peanut and certain tree nuts, as well as among tree nuts though such patterns do not always result in clinically relevant allergy. Molecular diagnostic testing may be a future tool to help parse out the aforementioned patterns, but oral food challenges are still the gold standard for accurate diagnosis. Although potential desensitization treatments have emerged for peanut allergy, these have not been developed for other legumes and most tree nuts, and desensitization to peanut has not proven to have an effect on legume cross-sensitization.

Baseline Gastrointestinal Eosinophilia Is Common in Oral Immunotherapy Subjects With IgE-Mediated Peanut Allergy.

Rationale: Oral immunotherapy (OIT) is an emerging treatment for food allergy. While desensitization is achieved in most subjects, many experience gastrointestinal symptoms and few develop eosinophilic gastrointestinal disease. It is unclear whether these subjects have subclinical gastrointestinal eosinophilia (GE) at baseline. We aimed to evaluate the presence of GE in subjects with food allergy before peanut OIT. Methods: We performed baseline esophagogastroduodenoscopies on 21 adults before undergoing peanut OIT. Subjects completed a detailed gastrointestinal symptom questionnaire. Endoscopic findings were assessed using the Eosinophilic Esophagitis (EoE) Endoscopic Reference Score (EREFS) and biopsies were obtained from the esophagus, gastric antrum, and duodenum. Esophageal biopsies were evaluated using the EoE Histologic Scoring System. Immunohistochemical staining for eosinophil peroxidase (EPX) was also performed. Hematoxylin and eosin and EPX stains of each biopsy were assessed for eosinophil density and EPX/mm2 was quantified using automated image analysis. Results: All subjects were asymptomatic. Pre-existing esophageal eosinophilia (>5 eosinophils per high-power field [eos/hpf]) was present in five participants (24%), three (14%) of whom had >15 eos/hpf associated with mild endoscopic findings (edema, linear furrowing, or rings; median EREFS = 0, IQR 0-0.25). Some subjects also demonstrated basal cell hyperplasia, dilated intercellular spaces, and lamina propria fibrosis. Increased eosinophils were noted in the gastric antrum (>12 eos/hpf) or duodenum (>26 eos/hpf) in 9 subjects (43%). EPX/mm2 correlated strongly with eosinophil counts (r = 0.71, p < 0.0001). Conclusions: Pre-existing GE is common in adults with IgE-mediated peanut allergy. Eosinophilic inflammation (EI) in these subjects may be accompanied by mild endoscopic and histologic findings. Longitudinal data collection during OIT is ongoing.