Skin Prick Test Wheal Size Research Articles

A pediatric randomized, controlled trial of German cockroach subcutaneous immunotherapy

Cockroach allergy contributes to morbidity among urban children with asthma. Few trials address the effect of subcutaneous immunotherapy (SCIT) with cockroach allergen among these at-risk children. We sought to determine whether nasal allergen challenge (NAC) responses to cockroach allergen would improve following 1 year of SCIT. Urban children with asthma, who were cockroach-sensitized and reactive on NAC, participated in a year-long randomized double-blind placebo-controlled SCIT trial using German cockroach extract. The primary endpoint was the change in mean Total Nasal Symptom Score (TNSS) during NAC after 12 months of SCIT. Changes in nasal transcriptomic responses during NAC, skin prick test wheal size, serum allergen-specific antibody production, and T-cell responses to cockroach allergen were assessed. Changes in mean NAC TNSS did not differ between SCIT-assigned (n= 28) versus placebo-assigned (n= 29) participants (P= .63). Nasal transcriptomic responses correlated with TNSS, but a treatment effect was not observed. Cockroach serum-specific IgE decreased to a similar extent in both groups, while decreased cockroach skin prick test wheal size was greater among SCIT participants (P= .04). A200-fold increase in cockroach serum-specific IgG4 was observed among subjects receiving SCIT (P< .001) but was unchanged in the placebo group. T-cell IL-4 responses following cockroach allergen stimulation decreased to a greater extent among SCIT versus placebo (P= .002), while no effect was observed for IL-10 or IFN-γ. A year of SCIT failed to alter NAC TNSS and nasal transcriptome responses to cockroach allergen challenge despite systemic effects on allergen-specific skin tests, induction of serum-specific IgG4 serum production and down-modulation of allergen-stimulated T-cell responses.

Clinical Relevance of Lepidoglyphus destructor Sensitisation in Allergic Rhinitis: Nasal Provocation Test as in vivo Assessment

Background: Dust mites are the leading cause of respiratory allergic diseases worldwide. Allergy to storage mites (SMs) has mostly been related to occupational exposures. However, recent studies have shown that sensitisation to SM, such as Lepidoglyphus destructor (Lep d), is of considerable importance also in urban populations, with high prevalence in dust samples of domestic environments. Co-sensitisation between house dust mites (HDMs) and SM is now regarded as very frequent in some regions, and cross-reactivity between them seems to be narrow. Therefore, SM allergenic capacity is increasingly a subject of study. The nasal provocation test (NPT), as an in vivo technique, could be considered the gold standard for the clinical relevance assessment of an allergen, in polysensitised rhinitis patients. Objective: The objective of this study was to analyse the clinical relevance of the SM Lep d, by assessing the relationship between in vivo sensitisation and expression of allergic respiratory disease in an urban setting. Patients and Methods: In our study, we enrolled a total of 32 allergic patients with rhinitis (with or without asthma) with proven sensitisation by skin prick test (SPT) and specific IgE (sIgE) to HDMs and/or SM. Patients underwent NPT with Lep d using subjective (Lebel Symptom Score Scale) and objective measurements (peak nasal inspiratory flow [PNIF]) for assessment of nasal response. Results: Most of the patients with positive SPT and sIgE to Lep d had a positive NPT (24/27; 89%). True Lep d allergy, assessed by a positive NPT, could be predicted by a SPT wheal size >9.7 mm and a sIgE >0.42 kUA/L, with 100%/95.7% sensitivity and 75.0%/83.3% specificity, respectively. Co-sensitisation between Lep d and Der p was high, 75.0%. Asthma was more frequent in the positive Lep d NPT group (54 vs. 12%, p < 0.05). Significantly more patients from this group reported physical exercise, nonspecific irritants, and respiratory infections as relevant triggers of respiratory symptoms (p < 0.01–p < 0.05). Conclusions: To our knowledge, this is the first study to show that sensitisation to Lep d may have clinical relevance in a non-occupational setting. In this group, there seems to be a relationship between allergy to Lep d and severity of respiratory disease, with more bronchial inflammation, when comparing with mite-allergic patients sensitised only to HDM. Therefore, the authors consider that sensitisation to Lep d should be considered when assessing and treating allergic respiratory disease in urban environments.

DNA methylation is not associated with sensitization to or dietary introduction of highly allergenic foods in a subset of the CHILD cohort at age 1 year.

In the first year of life, DNA methylation (DNAm) patterns are established and are particularly susceptible to exposure-induced changes. Some of these changes may leave lasting effects by persistently altering gene expression or cell type composition or function, contributing to disease. In this discovery study, we investigated DNAm associations with sensitization to peanut, egg, or cow's milk and hypothesized that genes demonstrating DNAm differences in immune cells may play a role in the development of food sensitization. Infant sensitization (a skin prick test wheal size that is at least 2 mm greater than the negative control) was measured to peanut, egg, and cow's milk at age 1 year, and ages of food introduction were reported prospectively. PBMC DNAm was measured in blood samples at 1 year in 144 infants, oversampled for atopy or wheeze. Statistical analysis of Illumina 450k array DNAm data was conducted in R with adjustment for clinical and genetic covariables and a minimum effect size of 1%, false discovery rate of 5%, and medium-confidence false discovery rate threshold of 20%. There were no DNAm differences between infants with and without peanut, egg, or cow's milk sensitization. Borderline significant sites with high effect sizes were enriched for methylation quantitative trait loci, hinting at genetic factors influencing DNAm at these sites. DNAm patterns did not differ by peanut or egg introduction before or after 12 months. This small pilot study did not show differences inmethylation by food sensitization or introduction, but it diddemonstrate DNAm patterns linked to genetic variants.

The importance of skin prick test in differentiating cat sensitivities and allergies in children.

The incidence of cat allergies in children has increased over the years. Children with cat allergies have mostly reported respiratory symptoms. The skin prick test (SPT) is the most preferred method to demonstrate sensitization to allergens. However, not all children who develop cat sensitization due to environmental exposure become allergic to cats. In our study, we aimed to determine the frequency of sensitization to cat and cat allergy, cat-related symptoms, and the cut-off value for the SPT that may indicate cat allergy. Patients aged 2-18 years, who applied to the Health Sciences University İzmir Dr Behçet Uz Pediatrics and Surgery Training and Research Hospital and Balıkesir University Application and Research Hospital Pediatric Allergy outpatient clinics between January 01, 2019 and December 31, 2020, were included in the study. Patients who underwent SPT and found to be sensitized to cat allergen, were evaluated retrospectively. Clinical and laboratory findings of the patients were recorded. Receiver operating characteristics (ROC) analysis was performed to determine the cut-off value for the SPT. Sensitization to cat was detected in 140 (4%) out of 3499 patients who underwent SPT. The median age of the patients was 12 years (min-max: 5-18) and 67.1% were male. Eighty-eight (62.9%) patients were symptomatic upon contact with cats, predominantly with nasal symptoms. These patients had significantly larger cat SPT wheal size than asymptomatic patients. The cut-off value was determined as 5.5 mm with a sensitivity of 72.7% and a specificity of 61.5% (95% CI, 60.5%-78.4%). Symptoms resolved in about half of our patients by reducing contact with cats. The present study is the first to report the frequency and clinical findings of cat sensitizations and allergies in Turkish children. For effective treatment, cat allergy must be diagnosed. In this regard, the use of a practical, readily accessible 5.5 mm cut-off point on the SPT may be helpful.

Comparison of commercial allergen extract with various milk products of skin prick tests in diagnosing cow's milk protein allergy

Introduction: In this study, we aimed to solve the incompatibilities between the skin prick test (SPT) result and the clinical picture encountered among patients. Thus, we used various milk products (raw, ultrahigh temperature [UHT], and pasteurized cow's milk) with commercial milk allergen extract in patients we think may have cow's milk protein allergy (CMPA) and made a comparison among the milk types. Methods: This study was conducted retrospectively between February 1, 2019, to June 1, 2019, at a pediatric allergy polyclinic of the university training/research hospital. A pair of 79 individuals, as control and patient groups, ages between 1 month and 21 years who were presented with a suspicion of CMPA and defined with SPT and/or allergen-specific immunoglobulin E (IgE) levels were included in the study. Allergen-specific IgE tests (specific IgE cow's milk, β-lactoglobulin, α-lactalbumin, casein) were evaluated. SPT was performed with fresh/raw, UHT, and pasteurized (daily) cow's milk besides the standard used commercial extract. Results: In the group included in the study and defined as IgE-mediated CMPA, 52.9% of the 79 patients were boys (n = 46), 47.1% were girls (n = 33), and the median age was 6 months (5.0-8.0 months). In the group of specific IgE cow's milk reaction that was sought, frequency and wheal (induration) size of SPT reaction to fresh/raw milk was also found to be statistically significant between positive- and negative-reaction groups, not detected against other milk products. The area under the curve for the diagnostic value of fresh milk was 93.1%. For the cutoff value of 2.50 mm, 88.1% sensitivity and 90.8% specificity were determined. In the group of specific IgE β-lactoglobulin reaction searched, there was a statistically significant difference in the frequency of SPT positivity and wheal size against UHT, fresh, and daily/pasteurized milk between positive and negative reaction groups. When the correlations of the mean induration axis in the tests were examined, it was found that, among raw milk, daily milk, cow's milk allergen extract, and UHT milk, a strong positive correlation was also statistically significant. Conclusion: The positivity that could not be detected with SPT when using allergen extract in a patient with positive specific IgE cow's milk result in the clinic can be detected with SPT made with fresh (raw) milk, which can be an alternative. In addition, specific IgE β-lactoglobulin seems to be the most compatible with the SPT wheal size (induration) of other milk types rather than extract. Comparative studies of SPT allergen extracts and various milk types used in the diagnosis of CMPA are very scarce in the literature, and more studies are needed on this subject.

Oral food challenge outcomes in children and adolescents in a tertiary centre: A 5-year experience.

Oral food challenges (OFC) are an important tool in the assessment of food allergy. We sought to identify factors available at initial assessment visit which were associated with successful outcome or challenge failure in Australian children. We conducted a retrospective review of all paediatric patients who underwent OFC in our allergy service over a 5-year period. Clinical data comprising patient demographics, co-morbidities, skin prick test (SPT) results, nature of previous reactions, elapsed time since previous reactions and outcome at OFC were recorded. Four hundred and fifty-six OFCs were conducted, with 56 cases (12.3%) resulting in a reaction. Likelihood of reaction at OFC was significantly increased for patients with atopic dermatitis (odds ratio 1.99). When stratified by food substance, atopic dermatitis had the strongest association with reaction within the peanut group (odds ratio 3.2), and no association was demonstrated for soy or prawn. Increasing SPT wheal size (P < 0.001) and previous history of anaphylaxis to the challenge food (P < 0.001) correlated with failure at OFC. A low-risk group was identified, of patients with no clear history of prior reaction to the challenge food, and SPT result <3 mm. Factors identified at assessment visit which correlated with reaction at OFC are atopic dermatitis, prior history of anaphylaxis, and increasing SPT wheal size. Domiciliary OFC could be considered in a select low-risk group of patients undergoing food challenge. This study was performed at a single centre with limited sample size, further large-scale and multicentre study verification of our data will provide more accurate representation of the Australian demographic.

Cow’s milk allergy skin tests: fresh milk, commercial extracts, or both?

BackgroundThe diagnosis of food allergy is based on a history of immediate allergic reaction following food ingestion, and skin prick test (SPT) demonstrating sensitization with commercial extracts (CE) or fresh food (FF). For most food allergens, the SPT with FF is considered more accurate and predictive. Regarding cow’s milk, the results are inconclusive. This retrospective study aimed to evaluate the accuracy of SPT with fresh milk compared to CE (cow’s milk and casein) for evaluation of cow’s milk allergy (CMA).MethodsThis study summarized the medical records of children, diagnosed with CMA. The data include demographics, skin tests and oral food challenge results, as well as atopic comorbidities.ResultsRecords of 698 patients with the diagnosis of CMA were reviewed, 388 fulfilled the inclusion criteria. Overall, 134 patients (34.54%) had an additional atopic disease. The SPT wheal size with fresh milk was significantly larger than with CE (cow's milk and casein) at first evaluation or before oral food challenge (OFC). Combination of SPT results (CE and FF) gave the maximal odds ratio for reaction during OFC and SPT with fresh milk alone gave the minimal OR (34.18 and 4.74, respectively).ConclusionsSPT with CE for CMA evaluation is more reliable than SPT performed with fresh milk. In patients suspected of having IgE-mediated CMA, before deciding on performing OFC, it is advised to perform SPT with at least two different extracts, and always include casein. Fresh milk can serve as a backup if commercial extracts are not available. In cases that the SPT with fresh milk is 3 mm or less, there is 93.3% chance that the OFC will pass without reaction.Trial registration This study protocol was reviewed and approved by the Ethics Committee of Meir Medical Center, IRB Number 0083-18 MMC.

DIAGNOSIS AND MANAGEMENT OF FOOD ALLERGIC PATIENTS ACROSS SEVERITY AND ALLERGENS: A NATIONWIDE US SURVEY

<h3>Introduction</h3> Food allergies affect millions of Americans and may result in life-threatening outcomes. In this study we aimed to understand food allergy diagnosis and management patterns of US Allergists. <h3>Methods</h3> In November 2021, a nationwide survey was emailed to US-practicing allergists (N=2850) to determine their diagnosis and management patterns. Providers were screened to ensure management of at least 1 food-allergic patient per month, with >25% of patients representing a pediatric population. <h3>Results</h3> The survey was completed by 125 allergists; the majority of allergists (81%) were community practitioners who saw an average of 74 food-allergic patients per month, of which 58% were pediatric. Allergists' top priorities for managing patients included preventing serious allergic reactions and maximizing patients' quality of life. Only 40% of allergists rate the severity of food allergies in their patients: main factors to determine disease severity were the severity/type of symptoms, history of requiring intervention (epinephrine), and number of organ systems involved in the reaction following exposure. Less important factors were skin prick test wheal size, presence of comorbid allergic diseases, and impact on quality of life. <h3>Conclusion</h3> Among US-based allergists that manage food-allergic patients, preventing serious allergic reactions was a top priority. Less than half of allergists categorize food allergy severity, and reaction severity weighs predominantly in how the overall disease severity is characterized. Further research on the impact of how definitions of food allergy disease severity impact shared decision making is warranted.

High prevalence of lupin allergy among patients with peanut allergy: Identification of γ-conglutin as major allergen

BackgroundLupin is a protein-rich legume with a growing presence in the food market worldwide. With increased consumption, lupin allergy (LA) reports are also rising. Uncertainties exist on the cross-reactivity between peanut and lupin, the allergenic potential of different lupin species, and sensitization patterns among different populations. ObjectiveTo evaluate the molecular basis of LA and to determine lupin allergens from 3 different species that may be involved in peanut allergy (PA) cross-reactivity. MethodsA total of 43 subjects with PA, those with LA, or controls without food allergy were evaluated with skin prick tests (SPTs) and specific IgEs (sIgEs). Lupin-sensitized subjects were offered a lupin oral food challenge (OFC). Immunoblots and enzyme-linked immunosorbent assays were performed on sera from lupin-sensitized subjects. ResultsIn this study, 44% of the PA subjects were confirmed to have LA by OFC. Anaphylaxis was the most frequent manifestation after lupin consumption, with a minimal eliciting dosage of 1 g lupin flour. There was no difference in lupin sIgE or SPT wheal size between lupin-sensitized and confirmed LA subjects or in the severity of symptoms among confirmed LA subjects. Sera from lupin-sensitized subjects uniformly reacted to all 3 different lupin species. Immunoblotting and enzyme-linked immunosorbent assays revealed immunoglobulin E binding to α- and γ-conglutin in all analyzed sera, whereas α- and β-conglutin recognition was variable. ConclusionOur findings reveal a high prevalence of LA among PA subjects, emphasizing lupin must be labeled as an allergen in foods. Owing to high variability in lupin-sIgE and lupin-SPT results, LA diagnosis may require OFC. In our population, γ-conglutin is the major allergen of lupin.

Peanut anaphylaxis in 2022: Decoupling epinephrine usage from emergency department evaluation

Peanut anaphylaxis in 2022: Decoupling epinephrine usage from emergency department evaluation

Characteristics of patients diagnosed as non-allergic following food allergy oral immunotherapy referral.

Ascribing food allergy diagnosis to patients who are not allergic is well described, but its implications on oral immunotherapy (OIT) have not been studied. The aim was to study non-allergic patients referred for OIT. All patients who began OIT at Shamir Medical Center between November 2015 and August 2020 were included. Medical records were reviewed, and skin prick tests (SPT) and/or specific IgE were measured. Patients were challenged to the index food. Allergic and non-allergic patients were compared. A total of 1073 patients were studied (milk, n = 327; egg, n = 41; peanut, n = 272; sesame, n = 130; and tree nuts, n = 303) and 87 (8.1%) were found non-allergic (milk, n = 21; egg, n = 6; sesame, n = 5; peanut, n = 29; tree nuts, n = 26). Predictors of being not allergic were no previous reaction to the index food (OR = 3.3, p = 0.001), not having asthma (OR = 2.4, p = 0.001), or HDM sensitization (OR = 2.0, p = 0.007), male sex (OR = 2.3, p = 0.004), and a smaller SPT wheal size (OR = 1.5, p < 0.001). A substantial number of patients referred for OIT are mislabeled with food allergy, suffer from unjustly food limitations and impairments in quality of life, and "take up" OIT places of true allergic patients. Awareness of OIT centers to this phenomenon is important. A significant number (8.1%) of patients referred for OIT are found not allergic to the food they intended to treat. This study characterizes non-allergic patients referred for OIT (a lack of previous reaction to the index food, a smaller or negative SPT wheal size, and less atopic co-morbidities) and discusses the implications of such referrals. Increased awareness by OIT centers to potential non-allergic patients referred for OIT is required, including screening of patients before treatment initiation, to minimize unnecessary treatments of non-allergic patients.

Is Skin Prick Test (SPT) Better Than Specific IgE (sIgE) For Predicting Oral Food Challenge (OFC) Outcomes For Pediatric Patients With Pecan And Walnut Food Allergy?

There is paucity of literature exploring cutoff values for pecan/walnut SPT wheal size and sIgE to predict OFC outcomes. Our study is aimed to identify thresholds of SPT and sIgE to accurately diagnose allergic individuals to limit OFC use for diagnosis.

Prognosis of food-induced anaphylaxis in children: A single-center real-life study.

Background: Food allergies are known to resolve over time, but there is little information on the natural history of food-induced anaphylaxis (FIA). Objective: This study aimed to evaluate the natural history of FIA in children and determine the factors that affect prognosis. Methods: Children with FIA who were followed up for at least 3 years, between 2010 and 2020, were included. Patients' families were contacted by telephone to question their child's tolerance status and invite them for reevaluation if uncertain. The patients were grouped as tolerant or persistent according to parent reports or reevaluation results. Logistic regression analysis was performed to determine the factors that affected persistence. Results: The study included 185 patients (62.2% boys) with 243 anaphylactic reactions to various foods. Fifty-eight patients (31%) gained tolerance within a 3-year follow-up period. Tolerance rates were higher in patients with FIA to milk (40%) and egg (43.9%) compared with to tree nuts (18.8%), legumes (5.6%), and/or seafood (11.1%) (p < 0.001). In a multivariate analysis, risk factors for persistent FIA were multiple food anaphylaxis (odds ratio [OR] 3.755 [95% confidence interval {CI}, 1.134-12.431]; p = 0.030), total IgE > 100 kU/L (OR 5.786 [95% CI, 2.065-16.207]; p = 0.001), and skin-prick test wheal size > 10 mm (OR 4.569 [95% CI, 1.395-14.964]; p = 0 .012) at presentation. Conclusion: Approximately a third of the patients with FIA developed tolerance within 3 years. Clinicians should remember that children with food allergies, even anaphylaxis, may develop tolerance over time. Regular follow up and reevaluation of tolerance status are necessary to avoid unnecessary elimination.

COMPARISON OF WHEAL SIZE INDUCED BY BIFURCATED NEEDLE® AND SMARTPRACTICE® PRICK LANCET

There is reportedly a difference in the diameter of the skin reaction induced by different types of skin prick test (SPT) devices. We compared the SPT diagnostic accuracy and wheal size between a Bifurcated Needle® (BN) and SmartPractice® Prick Lancet (PL), which are commercially available in Japan. An SPT was performed on 15 adults with and 10 without subjective symptoms of cedar pollinosis who wished to be examined for Japanese cedar pollen (JCP) sensitization. The SPT was performed blindly with a BN or PL with 10mg/ml of histamine dihydrochloride, 50% glycerosaline control, and JCP extract solution (TORII PHARMACEUTICAL CO., LTD., Tokyo, Japan). The wheal sizes induced by the BN and PL were then compared. The JCP-specific IgE antibody titer was measured to compare the sensitivity and specificity of the SPT. Histamine wheal diameters were 6.0 (5.5-6.5) mm by BN and 6.0 (5.5-6.5) mm by PL (p=0.67), and none of the negative control solutions induced wheal. The respective sensitivity and specificity for cedar sensitization were 100% and 86% for BN, 100% and 79% for PL, and the areas under the ROC curve were 0.72 and 0.69 (p=0.32). The diagnostic accuracy of cedar pollen extract based on specific IgE-JCP sensitization and the diameter of the wheal produced by a BN and PL were considered equivalent.

The role of diagnostic tests and oral food challenge results to predict sesame allergy

BackgroundThe presence of sesame allergy and its importance are increasing. ObjectiveTo determine the results of sesame and tahini oral food challenges (OFCs) and whether sesame-specific immunoglobulin E and skin prick tests (SPTs) accurately predicted sesame allergy in children. MethodsPatients with suspected sesame allergy between June 1, 2018, and June 1, 2020, were examined. ResultsOf 92 patients (n = 65, 70.7% of the patients were boys) with a median age of 2 years (interquartile range, 1.2-3.8 years), 64 were reactive to tahini. Of 64 patients, 41 had a positive OFC result and 23 had a consistent history. Of 54 sesame OFCs, 10 patients had a positive outcome. Of 44 with a negative outcome of sesame OFC, 4 experienced allergic reactions with tahini at home and 22 patients had a positive result for tahini OFC. In multivariate logistic regression analysis, clinical reactivity of sesame (either a consistent history or a positive OFC) was positively associated with sesame SPT (odds ratio, 2.120; 95% confidence interval, 1.136-3.957; P = .01) and tahini SPT (odds ratio, 1.661; 95% confidence interval, 1.143-2.413; P = .008). Nevertheless, sesame-specific immunoglobulin E did not predict clinical reactivity. Tahini OFC outcomes were well predicted for both sesame and tahini SPTs (area under the curves of 0.937 and 0.896, respectively, P < .001 for both). A sesame SPT wheal size of 5.25 mm had 90.6% sensitivity, 82.1% specificity, and 5.1 positive likelihood ratio. For tahini SPT, the 6-mm threshold had 100% sensitivity, 82.1% specificity, and 5.6 positive likelihood ratio. ConclusionIn the OFC, tahini emerged as a more optimal diagnostic tool to avoid false negatives. Furthermore, both high sesame and tahini SPT levels individually can help predict the diagnosis of sesame allergy.

Which skin prick test wheal size detects true allergy to Salsola kali?

Background. Sensitization to Salsola kali (Sk) weed pollen allergen is the most common cause of seasonal allergic rhinitis (SAR) in Middle East countries. Aim. To identify Salsola kali skin prick test (SkSPT) wheal size cut-off, able to determine true allergy among adult patients with moderate to severe SAR, who are in need of Salsola kali allergen specific immunotherapy (SkAIT). Methods. In 151 adults with moderate to severe SAR, mean age 32.79 ± 10.79 years, of both gender (females: 43.05%), with a positive SkSPT, (i.e., cut off wheal longest diameter of 3 mm) and one or more other local weed pollens, Salsola kali nasal provocation test (SkNPT) was carried out. Response was assessed both subjectively, with scores, and objectively, by measuring peak nasal inspiratory flow (PNIF). Safety profile of SkNPT was assessed using peak expiratory flow rate (PEF) measurements. Results. SkNPT positive response was found in 125 patients (82.78%). Mean skin prick test (SPT) wheal size to Sk was bigger in the nasal provocatin test (NPT) positive group (9 mm) compared to the NPT negative patients (5 mm), p less than 0.0001. ROC analysis showed that a SPT wheal size to Sk at the threshold of > 7.5 mm enabled identification of SkNPT positivity with a sensitivity of 73.6% and specificity of 100.0% (area under the curve 0.9498, standard error 0.01808; 95% confidence interval (CI): 0.9144 to 0.9853; p less than 0.0001). Conclusions. SPT wheal size of 3 mm might overestimate the presence of real allergy to Sk in a desert environment. A SPT wheal size > 7.5 mm for Sk appears to distinguish individuals who develop disease from those who does not. Physicians should select the proper SPT wheal size value as an appropriate criterion according to the allergen than using a uniform cut off value in patients eligible for SkAIT.

Tolerance development in cow’s milk–allergic infants receiving amino acid–based formula: A randomized controlled trial

Tolerance development is an important clinical outcome for infants with cow's milk allergy. This multicenter, prospective, randomized, double-blind, controlled clinical study (NTR3725) evaluated tolerance development to cow's milk (CM) and safety of an amino acid-based formula (AAF) including synbiotics (AAF-S) comprising prebiotic oligosaccharides (oligofructose, inulin) and probiotic Bifidobacterium breve M-16V in infants with confirmed IgE-mediated CM allergy. Subjects aged ≤13 months with IgE-mediated CM allergy were randomized to receive AAF-S (n= 80) or AAF (n= 89) for 12 months. Stratification was based on CM skin prick test wheal size and study site. After 12 and 24 months, CM tolerance was evaluated by double-blind, placebo-controlled food challenge. Alogistic regression model used the all-subjects randomized data set. At baseline, mean± SD age was 9.36± 2.53 months. At 12 and 24 months, respectively, 49% and 62% of subjects were CM tolerant (AAF-S 45% and 64%; AAF 52% and 59%), and not differ significantly between groups. During the 12-month intervention, the number of subjects reporting at least 1 adverse event did not significantly differ between groups; however, fewer subjects required hospitalization due to serious adverse events categorized as infections in the AAF-S versus AAF group (9% vs 20%; P= .036). After 12 and 24 months, CM tolerance was not different between groups and was in line with natural outgrowth. Results suggest that during the intervention, fewer subjects receiving AAF-S required hospitalization due to infections.

Estimating the Risk of Severe Peanut Allergy Using Clinical Background and IgE Sensitization Profiles.

Background: It is not well-understood why symptom severity varies between patients with peanut allergy (PA).Objective: To gain insight into the clinical profile of subjects with mild-to-moderate and severe PA, and investigate individual and collective predictive accuracy of clinical background and IgE to peanut extract and components for PA severity.Methods: Data on demographics, patient history and sensitization at extract and component level of 393 patients with probable PA (symptoms ≤ 2 h + IgE sensitization) from 12 EuroPrevall centers were analyzed. Univariable and penalized multivariable regression analyses were used to evaluate risk factors and biomarkers for severity.Results: Female sex, age at onset of PA, symptoms elicited by skin contact with peanut, family atopy, atopic dermatitis, house dust mite and latex allergy were independently associated with severe PA; birch pollen allergy with mild-to-moderate PA. The cross-validated AUC of all clinical background determinants combined (0.74) was significantly larger than the AUC of tests for sensitization to extract (0.63) or peanut components (0.54–0.64). Although larger skin prick test wheal size, and higher IgE to peanut extract, Ara h 1 and Ara h 2/6, were associated with severe PA, and higher IgE to Ara h 8 with mild-to-moderate PA, addition of these measurements of sensitization to the clinical background model did not significantly improve the AUC.Conclusions: Models combining clinical characteristics and IgE sensitization patterns can help establish the risk of severe reactions for peanut allergic patients, but clinical background determinants are most valuable for predicting severity of probable PA in an individual patient.

Mechanisms of oral immunotherapy.

Food allergy presents a significant global health concern with up to 10% of the population affected in developed nations and a steadily increasing prevalence. In many cases, particularly with peanut, tree nut and shellfish, food allergy is a lifelong and potentially life-threatening diagnosis. While no 'cure' for IgE-mediated food allergy exists, oral immunotherapy (OIT) is a promising treatment modality with the peanut OIT drug Palforzia (Aimmune Therapeutics) the only treatment for food allergy that is currently approved by the United States Food and Drug Administration. OIT primarily induces a state of desensitization with only a minority of subjects achieving sustained unresponsiveness, a state of limited clinical remission that appears to be immunologically distinct from natural tolerance. Early humoural changes during OIT include an initial increase in allergen-specific IgE, which eventually decreases to below baseline levels as OIT progresses, and a gradual increase in allergen-specific IgA and IgG4 that continues throughout the course of OIT. Basophil hyporesponsiveness and decreased skin prick test wheal size are observed within the first year of OIT, and persistence after completion of therapy has been associated with sustained unresponsiveness. In the T-cell compartment, there is an initial expansion followed by a decline in the number and activity of T helper 2 (TH 2) cells, the latter of which may be dependent on an expansion of IL-10-producing cells, including regulatory T-cells. Our understanding of the immunomodulatory effects of OIT continues to evolve, with new technologies such as single-cell transcriptional profiling and antibody epitope analysis allowing for more detailed study of T-cell and B-cell responses to OIT. In this review, we present evidence to illustrate what is currently known about the immunologic changes induced by OIT, explore potential mechanisms and emphasize knowledge gaps where future research is needed.

Age and eczema severity, but not family history, are major risk factors for peanut allergy in infancy

Whether to screen high-risk groups before early peanut introduction is controversial. We sought to determine the risk of peanut allergy (PA) before peanut introduction for infants with (1) moderate-severe eczema, (2) another food allergy (FA), and/or (3) a first-degree relative with peanut allergy (FH). Infants aged 4 to 11 months with no history of peanut ingestion, testing, or reaction and at least 1 of the above risk factors received peanut skin prick test and, depending on skin prick test wheal size, oral food challenge or observed feeding. A total of 321 subjects completed the enrollment visit (median age, 7.2 months; 58% males); 78 had eczema only, 11 FA only, 107 FH only, and 125 had multiple risk factors. Overall, 18% of 195 with eczema, 19% of 59 with FA, and 4% of 201 with FH had PA. Only 1% of 115 with FH and no eczema had PA. Among those with eczema, older age (odds ratio [OR], 1.3; 95% CI, 1.04-1.68 per month), higher SCORing Atopic Dermatitis score (OR, 1.19; 95% CI, 1.06-1.34 per 5 points), black (OR, 5.79; 95% CI, 1.92-17.4 compared with white), or Asian race (OR, 6.98; 95% CI, 1.92-25.44) and suspected or diagnosed other FA (OR, 3.98; 95% CI, 1.62-9.80) were associated with PA. PA is common in infants with moderate-severe eczema, whereas FH without eczema is not a major risk factor, suggesting screening only in those with significant eczema. Even within the first year of life, introduction at later ages is associated with a higher risk of PA among those with eczema, supporting introduction of peanut as early as possible.