Diagnosis Of Peanut Allergy Research Articles

Allergy to sunflower seed and sunflower butter as proposed vehicle for sensitization.

BackgroundIt is hypothesized that household exposure to allergenic proteins via an impaired skin barrier, such as atopic dermatitis, may contribute to the development of IgE sensitization. Household presence of peanut is a risk factor for the development of peanut allergy in children. Sunflower seed butter is a peanut-free alternative to peanut butter, and sunflower seed allergy is an uncommon but reported entity.Case presentationA 3 year old boy presented with oral discomfort that developed almost immediately after he ate sunflower seeds for the first time. He was given a dose of diphenhydramine. Subsequently he vomited, and his symptoms gradually resolved. A similar episode occurred to a commercial snack made with sunflower seed butter. Skin prick testing demonstrated a large positive (10 mm wheal) wheal-and-flare response to a slurry of fresh sunflower seed within 3–4 minutes associated with severe pruritus.This child has an older sibling with confirmed peanut allergy (PNA). After the PNA diagnosis was made, the family home became peanut-free. In lieu of peanut butter, sunflower butter was purchased and eaten frequently by family members, but not by the child reported herein.Subsequent to the episodes above, the child ate a bread roll with visible poppy seeds and developed itchy throat, dyspnea, and urticaria. Epicutaneous skin testing elicited a >10 mm wheal size within 3–4 minutes in response to a slurry of whole poppy seeds and 8 mm to fresh pumpkin seed, which had never been consumed.ConclusionsA case of sunflower allergy in the context of household consumption of sunflower butter has not yet been reported. We suggest that homes which are intentionally peanut-safe may provide an environment whereby infants with impaired skin barrier are at increased risk of allergy to alternative “butter” products being used, via cutaneous exposure to these products preceding oral introduction to the child.

Use of a basophil activation test as a complementary diagnostic tool in the diagnosis of severe peanut allergy in adults.

BackgroundDiagnosis of severe peanut allergy is difficult and delays in making an accurate diagnosis may place the patient at risk. Adults with a history of anaphylaxis must strictly avoid any contact with peanuts or products that may contain traces of peanuts. For these persons, conventional evaluations with skin prick testing (SPT) and IgE tests may not be sufficient to assess the risk of anaphylaxis. Therefore, we investigated whether the basophil activation test (BAT) could be used for the diagnosis of severe peanut allergy in adults. We compared the non-invasive BAT with conventional laboratory diagnostic tests, including SPT and specific IgE to allergen extracts and components, for the diagnosis of severe peanut allergy.MethodsForty-seven persons with severe allergy to peanuts and a clinical diagnosis of anaphylaxis (PA-group), 22 subjects with peanut sensitization (PS-group) and 22 control (C-group) subjects, all in the age range of 18–60 years, were recruited retrospectively and prospectively into the study. Thirty-four patients with peanut allergy and 11 peanut-sensitized patients were sensitized to soy, while 36 patients in the PA-group and 20 patients in the PS-group were sensitized to birch pollen. All the patients and control subjects were investigated with BAT and SPT for responses to peanut, soy and birch extracts and their serum samples were assayed for the presence of specific IgE to peanut, soy and birch extracts, as well as IgE to allergen components (ISAC).ResultsIn a multivariate factor analysis, severe peanut allergy (PA) was positively associated with SPT to peanut, IgE to peanut, BAT to peanut and IgE to rAra h 1, 2, 3 and 6 peanut components, as well as to soy components (nGly m 5 and nGly m 6). In contrast, peanut sensitization was positively associated with increased levels of IgE to rAra h 8, birch and birch-related components. BAT-detected reactivity to peanut was significantly higher in patients who had a history of severe allergy to peanuts, as compared with patients who were sensitized to peanuts (p < 0.001), and the receiver operating curve (ROC) analysis showed that BAT had high sensitivity and specificity for predicting severe peanut allergy, with a ROC area under the curve of 0.862. However, in the PA-group, the BAT results for peanut correlated only weakly with the levels of IgE to rAra h 1, 2 and 3 and nAra h 6. Study limitations: oral provocation in the patients with a history of severe peanut allergy could not be performed to compare clinical reactivity with the BAT result due to ethical constraints. Neither was it possible to perform BAT with peanut recombinant allergens which were not available at the time the study commencedConclusionsBAT is useful in determining the severity of peanut allergy and may be used as a complementary diagnostic tool to ensure accurate diagnosis of severe peanut allergy in adults. Thus, it may reduce the need to subject these patients to further tests, including an open challenge with peanuts.Electronic supplementary materialThe online version of this article (doi:10.1186/s13601-015-0064-9) contains supplementary material, which is available to authorized users.

Heterogeneous responses and cross reactivity between the major peanut allergens Ara h 1, 2,3 and 6 in a mouse model for peanut allergy.

BackgroundThe relative contribution and the relation between individual peanut allergens in peanut allergic responses is still matter of debate. We determined the individual contribution of peanut proteins to B, T cell and allergic effector responses in a mouse model for peanut allergy.MethodsMice were immunized and challenged by oral gavage with peanut protein extract or isolated allergens Ara h 1, 2, 3 and 6 followed by assessment of food allergic manifestations. In addition, T cell responses to the individual proteins were measured by an in vitro dendritic cell-T cell assay.ResultsSensitization with the individual peanut proteins elicited IgE responses with specificity to the allergen used as expected. However, cross reactivity among Ara h 1, 2, 3 and 6 was observed. T cell re-stimulations with peanut extract and individual peanut proteins also showed cross reactivity between Ara h 1, 2, 3 and 6. Despite the cross reactivity at the IgE level, only Ara h 2 and 6 were able to elicit mast cell degranulation after an oral challenge. However, after systemic challenge, Ara h 1, 2 and 6 and to lesser extent Ara h 3 were able to elicit anaphylactic responses.ConclusionsAra h 1, 2, 3 and 6 sensitize via the intra-gastric route, but differ in their capacity to cause allergic effector responses. Interestingly, extensive cross reactivity at T cell and antibody level is observed among Ara h 1, 2, 3 and 6, which may have important implications for the diagnosis and therapy of peanut allergy. Awareness about the relative contribution of individual peanut allergens and cross reactivity between these allergens is of importance for current research in diagnostics and therapeutics for and the mechanism of peanut allergy.

Epidemiology of childhood peanut allergy.

Although peanut allergy is among the most common food allergies, no study has comprehensively described the epidemiology of the condition among the general pediatric population. Our objective was to better characterize peanut allergy prevalence, diagnosis trends, and reaction history among affected children identified from a representative sample of United States households with children. A randomized, cross sectional survey was administered to parents from June 2009 to February 2010. Data from 38,480 parents were collected and analyzed in regard to demographics, allergic symptoms associated with food ingestion, and methods of food allergy diagnosis. Adjusted models were estimated to examine association of these characteristics with odds of peanut allergy. Of the 3218 children identified with food allergy, 754 (24.8%) were reported to have a peanut allergy. Peanut allergy was reported most often among 6- to 10-year-old children (25.5%), white children (47.7%), and children from households with an annual income of $50,000-$99,999 (41.7%). Although peanut allergy was diagnosed by a physician in 76% of cases, significantly more peanut allergy reactions were severe as compared with reactions to other foods (53.7% versus 41.0%, p < 0.001). Parents were significantly less likely to report tolerance to peanut as compared with the odds of tolerance reported for other foods (odds ratio 0.7, 95% confidence interval: 0.5-0.9). Childhood peanut allergy, which represents nearly a quarter of all food allergy, presents more severe reactions and is least likely to be outgrown. Although it is diagnosed by a physician in nearly three-fourths of all cases, socioeconomic disparities in regard to diagnosis persist.

Ara h 2 and Ara h 6 sensitization predicts peanut allergy in Mediterranean pediatric patients.

Peanut allergy (PA) management was improved by the introduction of molecular allergology, but guidelines for Mediterranean patients are lacking. We aimed at evaluating peanut component-resolved diagnosis as a diagnostic and prognostic tool in children from Southern France. In 181 pediatric patients, PA diagnosis was founded on medical history, skin prick testing, serum-specific IgE to Arachis hypogea extract and components, Pru p 4, and plant carbohydrates, and oral food challenge. Allergen microarray was also performed in 68 of these patients. In peanut-allergic children (n = 117), IgE to Ara h 6 were most prevalent (64%), followed by Ara h 2 (63%), Ara h 1 (60%), and Ara h 9 (52%). Ara h 6 was the best predictor of PA. The second best predictor was the ratio of Ara h 2 IgE to peanut IgE (cutoff 0.113). Persistent childhood PA was associated with complex molecular profiles. Comparison of singleplex and microarray results showed poor concordance for Ara h 2 and Ara h 9. Ara h 6 and Ara h 2 are the best predictors of PA at diagnosis in Mediterranean pediatric patients. Ara h 1, Ara h 8, and molecular complexity are associated with PA persistence.

Changes in peanut allergy prevalence in different ethnic groups in 2 time periods

Changes in peanut allergy prevalence in different ethnic groups in 2 time periods

The natural history of peanut sensitization and allergy in a birth cohort

Information on the natural history of peanut-induced allergic sensitization (PAS) and clinical peanut allergy (PA) remains limited. Most previous studies selected children who were given a diagnosis of PA, which does not provide the population perspective and probably ignores those with low levels of sensitization.1,2 There are no population-based studies on the natural history of PAS or PA. To provide a population perspective, we used the Isle of Wight birth cohort (n = 1456) and determined the natural history of PAS and PA, focusing on incidence, persistence, and remission.

O-164 Specific Immunoglobulin E To Ara H 2 As Predictor For Peanut Allergy In Children In A General Dutch Hospital

Background Specific immunoglobulin E (sIgE) to Ara h 2 is described as a potential factor for diagnosing peanut allergy in children. However for the Dutch children, limited data are available. In this study the diagnostic value of sIgE to Ara h2 for children in a general non-university hospital is evaluated and compared with the existing data. Methods Data from 137 peanut sensitised children were collected retrospectively. The primary outcome was peanut allergy or tolerance confirmed by food challenges. Different possible predictors, including sIgE to Ara h 2 (n = 52), were identified by multivariate backward stepwise logistic regression analysis. All significant predictors were combined in a formula for prediction of peanut allergy. Different essential cut-off points were obtained by an ROC curve. Results Multivariate analysis resulted in sIgE to Ara h 2 as only predictor for peanut allergy, with a discriminative ability of 0.87 (95% CI, 0.77–0.97). Sensitivity and specificity values of respectively 55% and 95% were found at a sIgE to Ara h 2 cut-off value of 4.25 kU/L. Hundred percent specificity was reached at a cut-off point of 5.61 kU/L. The mean (SD) sIgE to Ara h 2 level for allergic children was 21.49 kU/L (SD 30.65) compared to 1.07 kU/L (1.56) for tolerant children (p = 0.001). Conclusions Specific IgE to Ara h 2 is the best predictor for peanut allergy in sensitised children in a non-university hospital, comparable to previously published data. These results are a step forward to a generalisation to the Dutch children population.

Galactose-alpha-1,3-galactose sensitization is a prerequisite for pork-kidney allergy and cofactor-related mammalian meat anaphylaxis

auto-injector (k 5 0.57, 95% CI 0.38-0.76), and less agreement between self-reported peanut allergy and peanut allergy defined by the 90% specificity decision point only (k5 0.49, 95%CI 0.310.68). Each epidemiologic method for assessing peanut allergy prevalencehas strengths and limitations.Double-blind, placebo-controlled food challenges are the gold standard for clinical peanut allergy diagnosis, but these are challenging to implement in large, unselected cohorts and have not been done in unselected US cohorts. As diagnostic adjuncts, component resolved diagnostics may also be increasingly implemented in epidemiologic cohorts going forward. In this letter, we have provided prevalence estimates according to several criteria that can be compared to one another and to previous estimates.Our results come fromaUScohort of children not selected for allergy or any disease, and they support that peanut allergy is an increasingly prevalent condition. Supinda Bunyavanich, MD, MPH Sheryl L. Rifas-Shiman, MPH Thomas A. E. Platts-Mills, MD Lisa Workman, BA Joanne E. Sordillo, ScD Matthew W. Gillman, MD, SM Diane R. Gold, MD, MPH Augusto A. Litonjua, MD, MPH

Peanut allergy prevalence among school-age children in a US cohort not selected for any disease

Peanut allergy prevalence among school-age children in a US cohort not selected for any disease

Basophil activation test discriminates between allergy and tolerance in peanut-sensitized children

BackgroundMost of the peanut-sensitized children do not have clinical peanut allergy. In equivocal cases, oral food challenges (OFCs) are required. However, OFCs are laborious and not without risk; thus, a test that could accurately diagnose peanut allergy and reduce the need for OFCs is desirable.ObjectiveTo assess the performance of basophil activation test (BAT) as a diagnostic marker for peanut allergy.MethodsPeanut-allergic (n = 43), peanut-sensitized but tolerant (n = 36) and non–peanut-sensitized nonallergic (n = 25) children underwent skin prick test (SPT) and specific IgE (sIgE) to peanut and its components. BAT was performed using flow cytometry, and its diagnostic performance was evaluated in relation to allergy versus tolerance to peanut and validated in an independent population (n = 65).ResultsBAT in peanut-allergic children showed a peanut dose-dependent upregulation of CD63 and CD203c while there was no significant response to peanut in peanut-sensitized but tolerant (P < .001) and non–peanut-sensitized nonallergic children (P < .001). BAT optimal diagnostic cutoffs showed 97% accuracy, 95% positive predictive value, and 98% negative predictive value. BAT allowed reducing the number of required OFCs by two-thirds. BAT proved particularly useful in cases in which specialists could not accurately diagnose peanut allergy with SPT and sIgE to peanut and to Arah2. Using a 2-step diagnostic approach in which BAT was performed only after equivocal SPT or Arah2-sIgE, BAT had a major effect (97% reduction) on the number of OFCs required.ConclusionsBAT proved to be superior to other diagnostic tests in discriminating between peanut allergy and tolerance, particularly in difficult cases, and reduced the need for OFCs.

Basophil response to peanut allergens in Mediterranean peanut-allergic patients.

Ara h 1, Ara h 2, and Ara h 3 are important sensitizers in peanut allergy. Ara h 9 has also been shown to be relevant in the Mediterranean area. We evaluated the basophil response to peanut allergens and Pru p 3 in Mediterranean patients: Group 1, peanut and peach allergy; Group 2, peanut allergy and tolerance to peach; Group 3, peach allergy and tolerance to peanut; Group 4, nonallergic subjects that tolerate both peanut and peach. Compared to controls (Group 4), there was an increased basophil activation with Ara h 2 (P=0.031) and Pru p 3 (P=0.009) in Group 1 and with Ara h 1 (P=0.016), Ara h 2 (P=0.001), and Ara h 9 (P=0.016) in Group 2. Importantly, only Ara h 2 showed an increased activation (P=0.009) in Group 2 compared to Group 3. Ara h 2 is the best discriminating allergen for peanut allergy diagnosis in a Mediterranean population showing two patterns: patients also allergic to peach, responding to Ara h 2 and Pru p 3, and patients allergic only to peanut, responding to Ara h 1, Ara h 2, and Ara h 9.

The diagnostic accuracy of specific IgE to Ara h 6 in adults is as good as Ara h 2

Specific IgE (sIgE) to Ara h 2 is useful in diagnosing peanut allergy. Our aim was to assess the diagnostic value of sIgE to Ara h 6, another 2S albumin, in an adult population suspected of peanut allergy. Subjects with suspected peanut allergy between 2002 and 2013 were included if a diagnostic double-blind, placebo-controlled food challenge with peanut was performed. sIgE to Ara h 2 and Ara h 6 was measured by ImmunoCAP ISAC 112. Of 107 challenged subjects, 65 had a positive challenge (61%). The discriminative ability of sIgE to Ara h 2 and Ara h 6 was comparable: AUC 0.81 vs. 0.82. Positive predictive value for both tests was 95% using a cutoff value ≥1 ISU/l with poor corresponding sensitivity values (58% for Ara h 2, 62% for Ara h 6), but good specificity values (95% for both tests). In conclusion, the diagnostic value of sIgE to Ara h 6 on population level was as good as sIgE to Ara h 2. On individual level, however, 5% of the subjects showed contradicting results between both tests using a cutoff of 0.3 ISU/l, leading to a risk of misdiagnosis if only one of both tests is used.

Peanut allergy may be overdiagnosed in younger siblings of those with confirmed peanut allergy

Background Siblings of children with peanut allergy (PNA) are reported to have a higher prevalence of PNA than the general population. This prevalence may have both genetic and environmental influences, but may also reflect incorrect PNA diagnoses with less rigorous usage of confirmatory tests in siblings. The Peanut Allergy Registry (PAR), a Canadian database of individuals with PNA, was used to assess whether siblings born after the diagnosis of PNA in the index case (i.e., child with PNA) were more likely to have never been exposed to peanut (PN) and to be diagnosed without an appropriate clinical history or testing.

Importance of Ara h 6 in peanut allergy diagnosis

Results Twenty-two children (median age: 6.63 y.o.; IQR: 5.22-10.12) were classified as allergic in the basis of at least two convincing clinical reactions upon ingestion of PNT in the last two years. Sixty-nine children (median age: 8.01 y.o.; IQR: 6.01-11.27) were classified as tolerant on the basis of regular consumption of PNT. Positive SPT with commercial PNT extract was found in 86% of the allergic vs. 12% in the tolerant group (p=.000), sIgE for PNT extract was positive (>0.35 kU/L) in 100% of allergic (median: 10.40, IQR: 4.86-70.73) vs. 57% of tolerants (median: 1.69, IQR: 0.85-5.59) (p=.000). In MA-ISAC Ara h 6 was the allergen most frequently recognized (77%) (median: 8,50, IQR:4.29-33.70), followed by Ara h 2 (59%) (median: 17,30, IQR: 0.57-37.41). ROC curves showed the best diagnostic performance for Ara h 6 (AUC=0.852) followed by Ara h 2 (AUC=0.792). A cut-off point of Ara h 6 for maximal sensitivity (Se) and specificity (Sp) was set at 1.245 ISU (Se=0,727 and Sp= 0.971). Conclusions Although Ara h 2 has been regarded as the marker of clinical reactivity in children allergic to peanut, special attention has to be paid to Ara h 6, which has been shown to have better diagnostic performance.

Improving diagnostic performances of peanut allergy using novel molecular components

Accurate in-vitro component-based diagnosis will allow clinicians to focus their efforts toward complex issues such as disease severity and reactive dose evaluation as well as establishing effective eviction measures. However to achieve this, clinical utility of component-resolved peanut allergy testing must be rigorously evaluated. In this pilot study, we compared performances of 2 component-resolved peanut allergy assays from Hycor® [H] and Thermo Scientific® [T] that are based on recombinant allergens (rAra h 1 [H/T], rAra h 2 [H/T], rAra h 3 [H/T], rAra h 6 [H], rAra h 7 [H], rAra h 8 [H/T] and rAra h 9 [H/T]). IgE reactivity to each allergen was measured in 34 clinically characterized patients: 26 peanut-allergic and 8 atopic subjects from Eastern and Northern France. Total peanut extract assay [T] yielded low performances even with a 0.35 kU/L cut-off (sensitivity: 92%, specificity: 25%). Quantifications of IgE to rAra h 1, rAra h 2 and rAra h 3 show a strong correlation between the two manufacturers (rAra h 1: r2 = 0.85, p < 10-3 ; rAra h 2: r2 = 0.96, p < 10-3; rAra h 3: r2 = 0.90, p < 10-3) and achieve the same level of performances independently of the allergen source. Among these three assays, rAra h 2 [H/T] yielded a sensitivity of 85% and a specificity of 100% with a 0.35 kU/L cut-off. The rAra h 6 assay is available from Hycor® only and yielded a sensitivity of 92% and a specificity of 100% using the same cut-off, i.e. 24/26 peanut allergic patients are positive for rAra h 6. The IgE from the 2 undiagnosed patients do not react with any of the other recombinant from any sources. Neither Hycor® nor Thermo Scientific® rAra h 8 assays are clinically useful for peanut allergy diagnosis in spite of their specificity differences at 50% and 25% respectively. Thermo Scientific® rAra h 9 assay was not clinically useful with no positive sample detected. Hycor® rAra h 9 assay detected 2 of the 26 peanut allergic patients without reactivity in the atopic patients (specificity: 12%, sensitivity: 100%). This is consistent with the low prevalence of Ara h 9 sensitisation in Northern Europe. This study suggests the possibility of improving the clinical utility of molecular component assays by substituting rAra h 6 to rAra h 2. It also introduces rAra h 9 as a novel component that might be a significant clinical value in countries outside Northern Europe. This will be evaluated in multicenter studies.

The fraction of exhaled nitric oxide improves prediction of clinical allergic reaction to peanut challenge in children

Retrospective studies of childhood peanut allergy demonstrate serum-specific IgE (IgE) levels against the peanut allergen Ara h2 may help predict a clinical reaction at food challenge. Fraction of exhaled nitric oxide (FeNO) is a non-invasive tool correlating to allergic airways inflammation and has been independently associated with increased food-specific IgE. To assess the validity of serum-specific Ara h2 IgE measured prospectively to diagnose peanut allergy and explore the utility of FeNO as a non-invasive screening tool for childhood food challenge. We recruited 53 participants from a cohort of consecutive children scheduled for an open-labelled peanut food challenge (OFC) by their paediatric allergist. Participants underwent skin prick test (SPT) measurement for sensitization to whole peanut extract, and serum was collected for Ara h2-specific IgE. FeNO was also measured in all cooperative children before the challenge. OFC and assessment of reaction were undertaken by clinicians blinded to test results. Ara h2-specific IgE and FeNO each showed improved diagnostic accuracy when compared to SPT. Receiver operator characteristic curve analysis gave an area under the curve (AUC) for Ara h2 sIgE of 0.84 (95% CI, 0.72-0.96). The AUC for FeNO, 0.83 (95% CI, 0.71-0.95), was equivalent to that of Ara h2. Combined AUC for SPT, sIgE to Ara h2 and FeNO was 0.96 (95% CI 0.90-1.00). There was no correlation between FeNO and serum nitrite levels (rs=-0.13, P=0.6, n=18). Prospectively measured Ara h2-specific IgE improves diagnostic accuracy and reduces unsuccessful challenge to peanut. FeNO levels may provide improved diagnostic accuracy in a paediatric population undergoing OFC. The proposed FeNO-based diagnostic algorithm requires further validation studies.

Comparing The Utility Of Skin Prick Testing Using Commercial Extracts and Fresh Food In Diagnosing Peanut Allergy

Comparing The Utility Of Skin Prick Testing Using Commercial Extracts and Fresh Food In Diagnosing Peanut Allergy

Ara h 2 and The Relative Risk Of Other Sensitizations

IgE sensitization to the peanut seed storage protein (SSP) Ara h 2 is the most accurate single serological test for the diagnosis of peanut allergy. This study shows the relative risk of sensitization to other components that may influence a diagnostic strategy.

日本人小児のピーナッツアレルギー診断における精製ピーナッツ抗原特異的好塩基球活性化試験（BAT）の有用性についての検討

日本人小児のピーナッツアレルギー診断における精製ピーナッツ抗原特異的好塩基球活性化試験（BAT）の有用性についての検討