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Background: Specific IgE to Ara h 2 is a diagnostic test for peanut allergy which may reduce the need for double-blind placebo-controlled food challenges (DBPCFC); however, guidance for using Ara h 2 in place of DBPCFCs has not been validated., Objective: To prospectively evaluate 1) diagnostic accuracy of previously published Ara h 2 cut-off levels to diagnose peanut allergy in children and 2) costs., Methods: A consecutive series of 150 children age 3.5 to 18 years was evaluated in secondary and tertiary settings in the Netherlands. sIgE to Ara h 2 was the index test, and oral peanut ingestion was the reference test. Oral peanut ingestion was home or supervised introduction for Ara h 2 ≤ 0.1, DBPCFC for 0.1-5.0 and open food challenge for ≥5.0. Costs were calculated using financial healthcare data., Results: A conclusive reference test was performed in 113 children (75%). Sixty-four children (57%) had peanut allergy, as confirmed by a DBPCFC (27/47) or an open challenge (37/50). Forty-nine children (43%) were considered peanut-tolerant after peanut introduction (19/19), a DBPCFC (20/47) or an open challenge (10/50). Area under the curve for Ara h 2 was 0.94 (95% CI 0.90-0.98). The diagnostic flow chart correctly classified 26/26 (100%; 84-100) of children with Ara h 2 ≤ 0.1 as peanut-tolerant and 34/35 (97%; 83-100) of children with Ara h 2 ≥ 5.0 as peanut-allergic. At a cut-off of ≤0.1 and ≥5.0, a sensitivity of respectively 100% (93-100) and 53% (38-67) was observed and a specificity of 53% (38-67) and 98% (87-100). Mean annual costs of the flow chart were estimated as €320-€636 per patient lower than following national allergy guidelines., Conclusions: In this diagnostic accuracy study, which did not take into account pretest probability, we have validated previously published Ara h 2 cut-off levels which are associated with peanut tolerance and allergy., (© 2021 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

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 evaluate the diagnostic value of (combined) peanut components and validate a previously 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 (2002-2012) and 70 new patients (2012-2019). Specific IgE (sIgE) 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% confidence interval) 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 kU A /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., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: To improve food labelling strategies, information regarding eliciting doses (EDs) and the effect of patient characteristics on these EDs is necessary., Objective: To establish EDs for objective and subjective symptoms and analyse the effect of sensitization levels and other patient characteristics on threshold distribution curves (TDCs)., Methods: Threshold data from 100 adults and 262 children with a positive food challenge were analysed with interval-censoring survival analysis (ICSA) and fitted to a TDC from which EDs could be extracted. Possible influencing factors were analysed as covariates by ICSA. A hazard ratio (HR) was calculated in case of a significant effect., Results: TDCs for both objective and subjective symptoms were significantly different between adults and children (P < 0.001). Objective ED05 values, however, were comparable (2.86 mg peanut protein in adults and 6.38 mg in children). Higher levels of sIgE to Ara h 2 and peanut extract were associated with a larger proportion of patient groups reacting to a dose increase with objective symptoms (adults and children) or subjective symptoms (adults, in children a trend). Age had a similar effect in children (HR 1.05 for objective symptoms and 1.09 for subjective symptoms). Gender had no effect on TDCs., Conclusion and Clinical Relevance: Subjective and objective TDCs were different between adults and children, but objective ED05 values were comparable, meaning that threshold data from children and adults can be combined for elaboration of reference doses for risk assessment. Higher sIgE levels to Ara h 2 and peanut extract were associated with a larger proportion of both patient groups to react to a certain dose increase., (© 2015 John Wiley & Sons Ltd.)

Background: A negative double-blind placebo-controlled food challenge (DBPCFC) should normally be followed by reintroduction of the food. However, reintroduction fails in a subset of children. The observed reintroduction problems could be due to refusal of the food that long has been avoided, to other behavioural/psychological factors or to false negative DBPCFC outcome. This study analyses the frequency, causes and risk factors for reintroduction failure in children after negative peanut DBPCFC., Methods: A retrospective study of children with a negative DBPCFC for peanut was performed. During follow-up after DBPCFC, parents were systematically interviewed about the current diet, symptoms and problems during reintroduction, and reactions to peanut after the reintroduction period. Successful reintroduction was defined as eating peanut or products containing peanut as ingredient on a regular basis., Results: Follow-up data were obtained in 103 children with a negative peanut challenge. In 70 (68%) children, reintroduction was successful (54 children tolerated peanut, 16 children tolerated peanut as ingredient). Reintroduction failed in 33 (32%) children. Food refusal (45%) and peanut-related symptoms (33%) were the most reported reasons. Risk factors for reintroduction failure were an elimination diet for more than three other foods (p = 0.019), a long elimination diet for peanut (p = 0.048) and peanut-related symptoms at home (p = 0.002)., Conclusion: Reintroduction failure is a common problem in children after negative peanut challenge. To guide reintroduction and identify potential peanut-related symptoms at home, careful follow-up after negative DBPCFC is advised. When symptoms occur or persist, food challenge outcome needs to be reconsidered., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Limited and contrasting data are available about risk factors for severe reactions during double-blind, placebo-controlled food challenge (DBPCFC). Knowing these risk factors would help to improve safety precautions and choosing the best setting for challenge. We assessed whether we could determine predictors for positive and severe food challenge outcome (FCO) with regular available patient data in children suspected for peanut allergy., Methods: A retrospective study in children referred for DBPCFC with peanut was performed during a 3-year period. Reactions during challenge were classified as mild/moderate (Sampson's grade 1-3) and severe (Sampson's grade 4-5). We performed uni- and multivariable logistic regression to determine predictors for positive and severe FCO., Results: A group of 225 children with a median age of 6.7 (IQR 5.0-9.5) years were studied. In 109 (48%) children, food challenge outcome was positive and 24 (11%) children developed a severe reaction. The level of sIgE for peanut OR 1.14 (1.08-1.20), male gender OR 0.40 (0.20-0.81), having another food allergy OR 0.43 (0.20-0.88), were independently related to positive FCO. No significant differences were found between children with severe and non-severe FCO with respect to age, gender, asthma, sIgE, or previous reaction to peanut., Conclusions: Although predictors of positive FCO could be identified, none of the studied risk factors could predict a severe reaction during peanut challenge. When challenging a child sensitized to peanut, clinicians should be prepared and equipped to handle any reaction in all cases., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Replacement of peanut extracts by recombinant peanut components is an important step in allergy serologic testing. Criteria are needed for the unbiased inclusion of patients into a study to validate such a replacement., Methods: Plasma samples from 64 peanut-positive children (42 reactors, 22 nonreactors in a double-blind, placebo-controlled food challenge) were used to compare IgE reactivity to six recombinant peanut allergens with reactivity to natural peanut proteins extracted at neutral or low pH. We tested the hypothesis that poor extractability of Ara h 9 and other basic allergens at neutral pH leads to under-representation of patients with such sensitization., Results: IgE reactivity to the components did not fully explain IgE reactivity to peanut extract in 5 of 32 reactors with IgE to peanut extract ≤100 kUA /l. IgE reactivity to components was stronger than to the extract in 11 plasma samples, which was largely due to a low Ara h 8 reactivity of the extract. IgE reactivity to Ara h 9 was much lower than reactivity to other basic proteins, some of which bound IgE well in the RAST, but lost IgE reactivity upon immunoblotting., Conclusions: Conventional peanut extracts are deficient in significant IgE-binding components. The inclusion of patients for a validation study should be based on serology performed with improved peanut reagents to avoid a bias against these under-represented, potentially important allergens. To judge clinical relevance of an allergen, the reagent used for inclusion of patients needs to be efficient in detecting IgE to this component., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: A diagnostic prediction model for peanut allergy in children was recently published, using 6 predictors: sex, age, history, skin prick test, peanut specific immunoglobulin E (sIgE), and total IgE minus peanut sIgE., Objectives: To validate this model and update it by adding allergic rhinitis, atopic dermatitis, and sIgE to peanut components Ara h 1, 2, 3, and 8 as candidate predictors. To develop a new model based only on sIgE to peanut components., Methods: Validation was performed by testing discrimination (diagnostic value) with an area under the receiver operating characteristic curve and calibration (agreement between predicted and observed frequencies of peanut allergy) with the Hosmer-Lemeshow test and a calibration plot. The performance of the (updated) models was similarly analyzed., Results: Validation of the model in 100 patients showed good discrimination (88%) but poor calibration (P < .001). In the updating process, age, history, and additional candidate predictors did not significantly increase discrimination, being 94%, and leaving only 4 predictors of the original model: sex, skin prick test, peanut sIgE, and total IgE minus sIgE. When building a model with sIgE to peanut components, Ara h 2 was the only predictor, with a discriminative ability of 90%. Cutoff values with 100% positive and negative predictive values could be calculated for both the updated model and sIgE to Ara h 2. In this way, the outcome of the food challenge could be predicted with 100% accuracy in 59% (updated model) and 50% (Ara h 2) of the patients., Conclusions: Discrimination of the validated model was good; however, calibration was poor. The discriminative ability of Ara h 2 was almost comparable to that of the updated model, containing 4 predictors. With both models, the need for peanut challenges could be reduced by at least 50%., (Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Background: Current labeling practices for allergenic foods like peanut can be inadequate. For future regulatory and industry guidelines, information on no-observed-adverse-effect levels (NOAELs) and eliciting doses (EDs) for allergenic foods is necessary., Objective: To determine NOAEL and ED in a representative group of peanut-sensitized children, relate these data to history and sensitization, and evaluate the outcome of dietary management., Methods: From an overall eligible group of 96 peanut-sensitized children, a representative group of 27 was evaluated by questionnaires, skin prick test, determination of specific IgE, and double-blind placebo-controlled food challenge (DBPCFC) with peanut according to the international consensus protocol, with 9 doses ranging from 10 microg to 3 g peanut flour. Dietary management was evaluated over a 12-month period., Results: Twenty-two children (81%) had a positive DBPCFC. The NOAEL in this group was 1 mg peanut flour, corresponding to 2 mg whole peanut. The ED for subjective symptoms (10 mg to 3 g) was significantly lower than for objective symptoms (100 mg to 3 g; P = .002). Severe reactions occurred only at high doses. EDs were not correlated to previous reactions by history, skin prick test, or specific IgE levels. All patients with a positive DBPCFC were advised to follow a strict diet. During the follow-up period, 10 patients had a less strict diet likely containing traces of peanut. In 3 cases, a mild reaction occurred with food products labeled "may contain peanut.", Conclusion: The NOAEL in a representative group of children with peanut allergy was 2 mg. Dietary compliance in half of this group was inadequate.