Pine nut allergy in children: A diagnostic test accuracy study

Abstract

To the Editor, Allergy to pine nut (seeds of genus Pinus trees) causes 3% of paediatric foodinduced anaphylaxis in Italy.1 In contrast to other nuts, where sensitization to crossreactive antigens is common,2 pine nut allergy is usually isolated.3 The main pine nut allergens are 2S albumins and vicilins, the latter triggering mainly local signs and symptoms.3 Diagnosis of pine nut allergy relies on clinical history, examination and specific testing using skin prick test, prickbyprick test (PbP), and/or serum specific IgE (sIgE) and, where necessary, oral food challenges (OFC).4 OFC is timeconsuming and can cause severe anaphylactic reactions.5 In this study, we evaluated the diagnostic test accuracy of pricktoprick skin test and sIgE to pine nuts in children. Charts from patients referred to the Allergy Unit of Meyer Children's University Hospital from December 2015 to March 2020 because of a suspected reaction to pine nuts or who had a positive PbP or sIgE to pine nuts as part of a tree nut allergy assessment were reviewed. All children who underwent an OFC to pine nuts were included in the study, and written informed consent was obtained from the children's parents for all procedures performed. Prickbyprick test to pine nut and other nuts (walnut, hazelnut, almond, cashew, peanut and pistachio) were performed with fresh nuts in all included patients.6 PbP was considered positive if the weal diameter was equal to or greater than 3 mm at 15 minreading. Histamine (10 mg/ml; Alk Abellò) and normal saline were used for positive and negative controls. sIgE was determined using a commercial assay (ImmunoCAP system, Thermo Fisher Scientific). Oral food challenges were open and not placebocontrolled, using 5 mg pine nut (0.7 mg of pine nut protein); then, the dose was doubled every 20 min until a reaction occurred or the total amount of about 20 pine nuts (about 588 mg of pine nut protein) was reached according to a modified protocol.7 As soon as any objective clinical manifestations were observed, the OFC was stopped, and the reaction was treated.4 OFC assessors were not blind to PbP and sIgE results. Epinephrine administration was used according to relevant guidelines.8 The median values of PbP and sIgE to pine nut were studied in the pine nut tolerant group and in the pine nut allergic group. Thus, we established the cutoff values for PbP and sIgE with the higher sensitivity, specificity, positive predictive values (PPV) and negative predictive value (NPV), as well as sensitivity, specificity, PPV and NPV of other potential cutoff values. Receiver operating characteristic (ROC) curve analyses were performed for PbP and sIgE. Correlation between sIgE and PbP to pine nut was assessed through linear regression and Spearman correlation index. Besides, we studied the role of sex, age, PbP or sIgE values in association with positive OFCs. Finally, we analysed the importance of clinical history in association with positive OFCs with pine nut when it was recorded as the culprit food. A multiple logistic regression analysis was performed that utilized the probability of reaction as an outcome variable and the clinical and demographic variables as covariates. Results were calculated through adjusted odds ratio (aOR) and a 95% Wald confidence interval (CI). Analyses used SAS (version 9.4; SAS Institute, Cary). Ninetyone children met the inclusion criteria, of whom 66 were pine nut tolerant and 25 pine nut allergic, including 17 with anaphylaxis, of whom 4 received intramuscular adrenaline. Mean age at OFC was 113.6 months (SD 46.2 months) in pine nut tolerant children and 103.7 months (SD 36.6 months) in those with pine nut allergy. Gender was also similar, with 64% male in both groups. Most of the children (91%) were atopic, but only 9/60 in the pine nut tolerant group had a previous history of pine nut reaction. Mean time from the reaction to OFC was 49.1 months (SD 42.7 months) in these 9 participants and 64.3 months (SD 24.9 months) in the 15/25 pine nut allergic participants with a previous history of reaction. The