Basophil activation test shows high accuracy in the diagnosis of peanut and tree nut allergy: The Markers of Nut Allergy Study.
Background: Peanut and tree nut allergies are the most important causes of anaphylaxis. Co-reactivity to more than one nut is frequent, and co-sensitization in the absence of clinical data is often obtained. Confirmatory oral food challenges (OFCs) are inconsistently performed. Objective: To investigate the utility of the basophil activation test (BAT) in diagnosing peanut and tree nut allergy. Methods: The Markers Of Nut Allergy Study (MONAS) prospectively enrolled patients aged 0.5-17 years with confirmed peanut and/or tree nut (almond, cashew, hazelnut, pistachio, walnut) allergy or sensitization fromCanadian (n=150) and Austrian (n=50) tertiary pediatric centers. BAT using %CD63+ basophils (SSClow/CCR3pos) as outcome was performed with whole blood samples stimulated with allergen extracts of each nut (0.001-1000ng/mL protein). BAT results were assessed against confirmed allergic status in a blinded fashion to develop a generalizable statistical model for comparisonto extract and marker allergen-specificIgE. Results: A mixed effect model integrating BAT results for 10 and 100 ng/mL of peanut and individual tree nut extracts was optimal. The area under the ROC curve (AUROC) was 0.98 for peanut, 0.97 for cashew, 0.92 for hazelnut, 0.95 for pistachio, and 0.97 for walnut. The BAT outperformed sIgE testing for peanut or hazelnut and was comparable for walnut (AUROC 0.95, 0.94, 0.92) ina sub-analysis in sensitized patients undergoing OFC. Conclusions: BAT can predict allergic clinical status to peanut and tree nuts in multi-nut sensitized children and may reduce the need for high-risk OFCs in patients.
The Global Burden of Illness of Peanut Allergy: A Comprehensive Literature Review.
Peanut allergy (PA) currently affects approximately 2% of the general population of Western nations and may be increasing in prevalence. Patients with PA and their families/caregivers bear a considerable burden of self-management to avoid accidental peanut exposure and to administer emergency medication (adrenaline) if needed. Compared with other food allergies, PA is associated with higher rates of accidental exposure, severe reactions, and potentially fatal anaphylaxis. Approximately 7-14% of patients with PA experience accidental peanut exposure annually, and one-third to one-half may experience anaphylaxis, although fatalities are rare. These risks impose considerably high healthcare utilisation and economic costs for patients with PA and restrictions on daily activities. Measures to accommodate patients with PA are often inadequate, with inconsistent standards for food labelling and inadequate safety policies in public establishments such as restaurants and schools. Children with PA are often bullied, resulting in sadness, humiliation, and anxiety. These factors cumulatively contribute to significantly reduced health-related quality of life for patients with PA and families/caregivers. Such factors also provide essential context for risk/benefit assessments of new PA therapies. This narrative review comprehensively assessed the various factors comprising the burden of PA.
Induction of Peanut Allergy Through Inhalation of Peanut in Mice.
Peanut (PN) allergy is a common life-threatening disease; however, our knowledge on the immunological mechanisms remains limited. Here, we describe the first mouse model of inhalation-driven peanut allergy. We administered PN flour intranasally to naïve wild-type mice twice a week for 4 weeks, followed by intraperitoneal challenge with PN extract. Exposure of mice to PN flour sensitized them without addition of adjuvants, and mice developed PN-specific IgE, IgG1, and IgG2a. After challenge, mice displayed lower body temperature and other clinical signs of anaphylaxis. This inhalation model is an ideal system to allow for future examination of immunological mechanisms critical for the development of PN allergy.
Accurate prediction of peanut allergy in one-third of adults using a validated Ara h 2 cutoff.
Background: The diagnostic value of peanut components is extensively studied in children, but to a lesser extent in adults with suspected peanut allergy. The use of peanut components in daily practice may reduce the need for double-blind placebo-controlled food challenges (DBPCFCs), however validation studies are currently lacking. Objective: To 1) evaluate the diagnostic value of (combined) peanut components and 2) validate a previous found Ara h 2 cutoff level with 100% positive predictive value (PPV) in adults with suspected peanut allergy. Methods: Adults who underwent a peanut DBPCFC were included: 84 patients from a previous study (2002 to 2012) and 70 new patients (2012 to 2019). Specific IgE to peanut extract, Ara h 1, 2, 3, 6 and 8 was measured using ImmunoCAP. Diagnostic value was assessed with an area under the curve (AUC) analysis. Results: In total, 95 (62%) patients were peanut allergic. sIgE to Ara h 2 and Ara h 6 were the best predictors with an AUC (95% CI) of 0.85 (0.79-0.91) and 0.85 (0.79-0.92), respectively. The Ara h 2 cutoff level with 100% PPV (≥1.75 kUA/L) was validated in the 70 new patients. Thirty percent of all included patients could be classified correctly as peanut allergic using this validated cutoff level. Conclusion: sIgE to Ara h 2 and Ara h 6 have equally high discriminative ability. Peanut allergy can be predicted accurately in one-third of adults using a validated cutoff level of sIgE to Ara h 2.
Irradiated Tree Nut Flours for Use in Oral Immunotherapy.
Background: Tree nut allergies affect an estimated 1% of the United States population and is lifelong in 90% of allergic individuals. Oral immunotherapy (OIT) for food allergies is an effective method to induce desensitization in a majority of participants in trials of peanut, egg, and milk OIT. Limited trials using tree nut OIT have been reported, possibly due to the lack of standardized drug products. Objective: Food products used in OIT are considered drugs by the FDA since they are intended to modulate the individuals' immune responses to the food allergens. As such, OIT drug products must meet FDA standards for acceptable levels of microbes and undergo testing for allergenic proteins. We aimed to determine the suitability of walnut, cashew, hazelnut, and almond flours for use in OIT trials. Methods: We employed gamma irradiation on commercially available walnut, cashew, hazelnut, and almond flours and tested their levels of microbial contamination, total protein and allergen content, along with stability of these parameters over time. Results: Our results demonstrate that irradiation of tree nut flours greatly diminishes the levels of total aerobic bacteria, mold, yeast, E. coli, and salmonella, while there are no substantial changes in total protein or allergen content. Importantly, the microbial levels, protein, and allergen content remained stable over a 24 month period. Conclusion: Irradiation of tree nut flours is a safe and effective method of processing to allow tree nut products to meet the FDA standards for OIT drug products.
The importance of the 2S albumins for allergenicity and cross-reactivity of peanuts, tree nuts and sesame seeds.
Allergies to peanuts, tree nuts, and sesame seeds are among the most important food related causes of anaphylaxis. Important clinical questions include: why is there a variable occurrence of co-allergy among these foods and is this immunologically mediated? Clinical and immunological data summarized here suggest an immunologic basis for these co-allergies based on similarities among the 2S-albumins. Data from component resolved diagnostics have highlighted the relationship between IgE binding to these allergens and the presence of IgE-mediated food allergy. Furthermore, in vitro and in vivo experiments provide strong evidence that the 2S albumins are the most important allergens in peanuts for inducing an allergic effector response. Although the 2S albumins are diverse, they have a common disulfide linked core with similar physicochemical properties that make them prime candidates to explain much of the observed co-allergy among peanuts, tree nuts and sesame seeds. The well-established frequency of cashew and pistachio nut co-allergy (64-100%) highlights how the structural similarities among their 2S albumins may account for observed clinical cross-reactivity. A complete understanding of the physicochemical properties of the 2S albumins in peanuts, tree nuts and sesame seeds will enhance our ability to diagnose, treat and ultimately prevent these allergies.
Practical challenges and considerations for early introduction of potential food allergens for prevention of food allergy.
Recent randomized controlled trials aimed at the prevention of food allergy have led to sweeping changes in food allergy prevention guidelines. Emphasis is now on the introduction of potential food allergens, particularly peanut and egg, rather than avoidance. Though guidelines recommend against delaying introduction of other potential allergens there remains little or no evidence of the benefit of their early introduction. Parents and physicians alike report a need for greater guidance and resources on early potential allergen introduction in the complementary feeding period. A thorough understanding of early introduction literature, current prevention guidelines, and infant nutrition will empower physicians to address patient needs and concerns both when advice is established as effective and where uncertainty remains. We discuss the state of the science, compare recommendations between guidelines, and provide practical options to introduce allergenic foods, alongside other complementary foods, within the first year of life. We include a review of the available literature, including review and suggestions of potential doses of food allergens, and the first published comparison of commercially available products and home-made early introduction foods to help clinicians support their patients. We address the nutritional, dietary and practical considerations of introducing food allergens in the first year of life, while adhering to infant feeding guidelines. Finally, given the limitations of existing guidelines, we review the need for shared decision-making (SDM) between physicians and parents regarding early allergen introduction.
Emerging Therapies for Peanut Allergy.
Peanut allergy (PA) is a food allergy that causes an IgE-mediated type I hypersensitivity reaction. PA has become an increasing public health burden, with 2% of American children reported to have this condition in 2010. Current guidelines recommend allergen avoidance, patient education, and administration of H1 antihistamines, β2-agonists, or epinephrine based on the severity of reaction. In this review article, emerging therapies for PA are evaluated for their potential role in treating PA. Oral, epicutaneous, and sublingual immunotherapies have completed clinical trials with promising efficacy. In particular, Palforzia (AR101) is an oral immunotherapy that received Food and Drug Administration (FDA)-approval in January 2020 and Viaskin Peanut is an epicutaneous immunotherapy with an anticipated FDA decision date by August 5, 2020. Furthermore, adjuvant combinations with either probiotics or anti-IgE receptor antagonists have shown an improved efficacy and safety profile compared to oral immunotherapy alone. However, immunotherapy-induced adverse reaction rates are high due to the risks associated with intentional allergen exposure. These results suggest that peanut immunotherapy has a promising role in the treatment of PA, although further studies are needed before its incorporation into standard of care.
Infant Allergy Testing and Food Allergy Diagnoses Before and After Guidelines for Early Peanut Introduction.
Background: A landmark 2015 trial on early exposure to peanuts led to expert recommendations for screening and early peanut introduction in high-risk (severe eczema and/or egg allergy) infants, but the impact of this paradigm shift on allergy testing and diagnosis is unknown. Objective: We assessed the effects of the Learning Early About Peanut Allergy (LEAP) trial and guideline publications on allergy testing and food allergy diagnoses in infants. Methods: In this retrospective cohort study, de-identified administrative health claims from a commercial and Medicare advantage claims database were used. Infants with at least one year of continuous coverage were selected using newborn codes for birth hospitalizations from January 2010 to June 2018. Interrupted time series models were used to compare the prevalence of allergy testing before and after LEAP publication in February 2015 and formal guideline publication in January 2017. Results: For 487,533 included infants, allergy testing increased after LEAP (risk ratio [RR]: 1.11 [95% CI, 1.07-1.15]) and guidelines (1.21 [1.18-1.23]). This increase of testing was also seen in infants not considered high-risk, both after LEAP (1.12 [1.08-1.17]) and guidelines (1.20 [1.16, 1.23]). For first-time allergy tests, post-guideline median number of allergens tested was 9 for serum tests and 10 for skin tests. Post-guidelines there was a significant increase in diagnosis of peanut (RR: 1.08 [1.00, 1.16]), egg (1.12 [1.05, 1.20]), and other food allergies (excluding milk) (1.22 [1.14, 1.31]). Conclusion: Allergy testing has increased, including in non-high-risk infants. Multi-allergen testing may be contributing to an increase in the diagnosis of other food allergies.
Peanut Allergy–No Longer a Life Sentence.
In this review we provide an overview on the latest knowledge in the prevention and active management of peanut allergy. The rise in incidence of food allergy has generated new challenges in the management of affected individuals. Strategies to counteract the increase in prevalence of peanut allergy can be considered as a pyramid, beginning with primary prevention of those at risk through earlier introduction of peanut into the infant diet, to secondary prevention of peanut-sensitised children through improvements in the correct diagnosis of peanut allergy and finally to the treatment of children with proven peanut allergy. CONCLUSION: With the paradigm shift towards an active management, peanut allergy should no longer be seen as a life sentence.