OBJECTIVES: To determine rates of other atopic manifestations in people with peanut allergy and the prevalence of such allergy in their families. DESIGN: A survey of people with self reported peanut allergy and people referred by their general practitioner for suspected peanut allergy; survey and skin testing of 50 children with reported peanut allergy and their available first degree relatives. SUBJECTS: 622 adults and children with reported, suspected, or known peanut allergy. MAIN OUTCOME MEASURES: Prevalence of peanut allergy and other allergies in the families of people with peanut allergy. RESULTS: 622 valid completed questionnaires were returned out of the 833 questionnaires dispatched (74.7%). All forms of atopy were both more common in successive generations (P < 0.0001) and more common in maternal than paternal relatives (P < 0.0001). Peanut allergy was reported by 0.1% (3/2409) of grandparents, 0.6% (7/1213) of aunts and uncles, 1.6% (19/1218) of parents, and 6.9% (42/610) of siblings. Consumption of peanuts while pregnant or breast feeding was more common among mothers of probands aged < or = 5 years than mothers of probands aged > 5 years (P < 0.001). Age of onset correlated inversely with year of birth (r = -0.6, P < 0.001). Skin prick testing of 50 children with reported peanut allergy and their families: 7 probands (14%) had a negative result for peanut. Peanut allergy was refuted by food challenge in all those tested (5/7). No parent and 13% (5/39) of siblings had a positive result on skin prick testing for peanut. Two of these siblings had negative challenge with peanuts. The prevalence of peanut allergy in siblings is therefore 3/39 (7%). CONCLUSIONS: Peanut allergy is more common in siblings of people with peanut allergy than in the parents or the general population. Its apparently increasing prevalence may reflect a general increase of atopy, which is inherited more commonly from the mother. Peanut allergy is presenting earlier in life, possibly reflecting increased consumption of peanut by pregnant and nursing mothers.
Filaggrin (FLG) loss-of-function mutations lead to an impaired skin barrier associated with peanut allergy. Household peanut consumption is associated with peanut allergy, and peanut allergen in household dust correlates with household peanut consumption.
We sought to determine whether environmental peanut exposure increases the odds of peanut allergy and whether FLG mutations modulate these odds.
Exposure to peanut antigen in dust within the first year of life was measured in a population-based birth cohort. Peanut sensitization and peanut allergy (defined by using oral food challenges or component-resolved diagnostics [CRD]) were assessed at 8 and 11 years. Genotyping was performed for 6 FLG mutations.
After adjustment for infantile atopic dermatitis and preceding egg skin prick test (SPT) sensitization, we found a strong and significant interaction between natural log (ln [loge]) peanut dust levels and FLG mutations on peanut sensitization and peanut allergy. Among children with FLG mutations, for each ln unit increase in the house dust peanut protein level, there was a more than 6-fold increased odds of peanut SPT sensitization, CRD sensitization, or both in children at ages 8 years, 11 years, or both and a greater than 3-fold increased odds of peanut allergy compared with odds seen in children with wild-type FLG. There was no significant effect of exposure in children without FLG mutations. In children carrying an FLG mutation, the threshold level for peanut SPT sensitization was 0.92 μg of peanut protein per gram (95% CI, 0.70-1.22 μg/g), that for CRD sensitization was 1.03 μg/g (95% CI, 0.90-1.82 μg/g), and that for peanut allergy was 1.17 μg/g (95% CI, 0.01-163.83 μg/g).
Early-life environmental peanut exposure is associated with an increased risk of peanut sensitization and allergy in children who carry an FLG mutation. These data support the hypothesis that peanut allergy develops through transcutaneous sensitization in children with an impaired skin barrier.
FLG loss-of-function mutations; filaggrin; skin barrier; peanut sensitization; peanut allergy; environmental peanut exposure; dust; threshold; AD, Atopic dermatitis; CRD, Component-resolved diagnostics; FLG, Filaggrin; GEE, Penalized generalized estimating equations methodology; ISU, ISAC standardized unit; LLQ, Lower limit of quantitation; MAAS, Manchester Asthma and Allergy Study; OFC, Oral food challenge; OR, Odds ratio; sIgE, Allergen-specific IgE; SPT, Skin prick test
Most 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.
To assess the performance of basophil activation test (BAT) as a diagnostic marker for peanut allergy.
Peanut-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).
BAT 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.
BAT 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.
Anaphylaxis; basophil activation test; CD203c; CD63; diagnosis; flow cytometry; food allergy; peanut allergy; ROC curve; BAT, Basophil activation test; CRD, Component-resolved diagnosis; DBPCFC, Double-blind placebo-controlled food challenge; fMLP, Formyl-methionyl-leucyl-phenylalanine; NA, Non–peanut-sensitized nonallergic; OFC, Oral food challenge; PA, Peanut-allergic; PPV, Positive predictive value; PS, Peanut-sensitized but tolerant; P-sIgE, Peanut-specific IgE; ROC, Receiver-operating characteristic; sIgE, Specific IgE; SPT, Skin prick test
Small studies suggest peanut oral immunotherapy (OIT) might be effective in the treatment of peanut allergy. We aimed to establish the efficacy of OIT for the desensitisation of children with allergy to peanuts.
We did a randomised controlled crossover trial to compare the efficacy of active OIT (using characterised peanut flour; protein doses of 2–800 mg/day) with control (peanut avoidance, the present standard of care) at the NIHR/Wellcome Trust Cambridge Clinical Research Facility (Cambridge, UK). Randomisation (1:1) was by use of an audited online system; group allocation was not masked. Eligible participants were aged 7–16 years with an immediate hypersensitivity reaction after peanut ingestion, positive skin prick test to peanuts, and positive by double-blind placebo-controlled food challenge (DBPCFC). We excluded participants if they had a major chronic illness, if the care provider or a present household member had suspected or diagnosed allergy to peanuts, or if there was an unwillingness or inability to comply with study procedures. Our primary outcome was desensitisation, defined as negative peanut challenge (1400 mg protein in DBPCFC) at 6 months (first phase). Control participants underwent OIT during the second phase, with subsequent DBPCFC. Immunological parameters and disease-specific quality-of-life scores were measured. Analysis was by intention to treat. Fisher's exact test was used to compare the proportion of those with desensitisation to peanut after 6 months between the active and control group at the end of the first phase. This trial is registered with Current Controlled Trials, number ISRCTN62416244.
The primary outcome, desensitisation, was recorded for 62% (24 of 39 participants; 95% CI 45–78) in the active group and none of the control group after the first phase (0 of 46; 95% CI 0–9; p<0·001). 84% (95% CI 70–93) of the active group tolerated daily ingestion of 800 mg protein (equivalent to roughly five peanuts). Median increase in peanut threshold after OIT was 1345 mg (range 45–1400; p<0·001) or 25·5 times (range 1·82–280; p<0·001). After the second phase, 54% (95% CI 35–72) tolerated 1400 mg challenge (equivalent to roughly ten peanuts) and 91% (79–98) tolerated daily ingestion of 800 mg protein. Quality-of-life scores improved (decreased) after OIT (median change −1·61; p<0·001). Side-effects were mild in most participants. Gastrointestinal symptoms were, collectively, most common (31 participants with nausea, 31 with vomiting, and one with diarrhoea), then oral pruritus after 6·3% of doses (76 participants) and wheeze after 0·41% of doses (21 participants). Intramuscular adrenaline was used after 0·01% of doses (one participant).
OIT successfully induced desensitisation in most children within the study population with peanut allergy of any severity, with a clinically meaningful increase in peanut threshold. Quality of life improved after intervention and there was a good safety profile. Immunological changes corresponded with clinical desensitisation. Further studies in wider populations are recommended; peanut OIT should not be done in non-specialist settings, but it is effective and well tolerated in the studied age group.
The management of peanut allergy relies on allergen avoidance and epinephrine autoinjector for rescue treatment in patients at risk of anaphylaxis. Biomarkers of severity and threshold of allergic reactions to peanut could significantly improve the care for patients with peanut allergy.
We sought to assess the utility of the basophil activation test (BAT) to predict the severity and threshold of reactivity to peanut during oral food challenges (OFCs).
The severity of the allergic reaction and the threshold dose during OFCs to peanut were determined. Skin prick tests, measurements of specific IgE to peanut and its components, and BATs to peanut were performed on the day of the challenge.
Of the 124 children submitted to OFCs to peanut, 52 (median age, 5 years) reacted with clinical symptoms that ranged from mild oral symptoms to anaphylaxis. Severe reactions occurred in 41% of cases, and 57% reacted to 0.1 g or less of peanut protein. The ratio of the percentage of CD63+ basophils after stimulation with peanut and after stimulation with anti-IgE (CD63 peanut/anti-IgE) was independently associated with severity (P = .001), whereas the basophil allergen threshold sensitivity CD-sens (1/EC50 × 100, where EC50 is half maximal effective concentration) value was independently associated with the threshold (P = .020) of allergic reactions to peanut during OFCs. Patients with CD63 peanut/anti-IgE levels of 1.3 or greater had an increased risk of severe reactions (relative risk, 3.4; 95% CI, 1.8-6.2). Patients with a CD-sens value of 84 or greater had an increased risk of reacting to 0.1 g or less of peanut protein (relative risk, 1.9; 95% CI, 1.3-2.8).
Basophil reactivity is associated with severity and basophil sensitivity is associated with the threshold of allergic reactions to peanut. CD63 peanut/anti-IgE and CD-sens values can be used to estimate the severity and threshold of allergic reactions during OFCs.
Basophil activation test; peanut; peanut allergy; threshold; severity; sensitivity; CD63; CD203c; CD-sens; double-blind; placebo-controlled food challenge; CD63 peanut/anti-IgE, Ratio of the percentage of CD63+ basophils at 100 ng/mL of peanut extract to the percentage of CD63+ basophils after stimulation with anti-IgE; CD-sens, Basophil allergen threshold sensitivity; DBPCPC, Double-blind, placebo-controlled peanut challenge; EC50, Half maximal effective concentration; LEAP, Learning Early About Peanut Allergy; PA, Peanut allergy; PE, Peanut extract; SPT, Skin prick test
OBJECTIVE: To determine the prevalence of sensitisation to peanuts and tree nuts in all children born during one year in one geographical area. DESIGN: Birth cohort study with structured review at ages 1, 2, and 4 years. SETTING: All children born on the Isle of Wight between January 1989 and February 1990. SUBJECTS: Of 1456 children originally included, 1218 were reviewed at age 4 years. Of these, 1981 had skin prick tests. MAIN OUTCOME MEASURES: Positive skin test results, clinical atopic disease, and risk factors for the development of atopy. RESULTS: 15 of 1218 (1.2%) children were sensitised to peanuts or tree nuts (13 to peanuts). Six had had allergic reactions to peanuts (0.5% of the population), one to hazelnuts, and one to cashew nuts; three had had anaphylactic reactions. Seven children had positive skin test results or detectable IgE to peanuts without clinical symptoms. Two children who reacted to peanut in infancy had lost their sensitivity by 4 years. Family history of atopy, allergy to egg (odds ratio 9.9, 95% confidence interval 2.1 to 47.9, and eczema (7.3, 2.1 to 26.1) were important predictors for peanut allergy. CONCLUSIONS: IgE mediated allergy to peanuts is common in early childhood. In many the allergy persists but a minority may develop tolerance.
The usefulness of peanut specific IgE levels for diagnosing peanut allergy has not been studied in primary and secondary care where most cases of suspected peanut allergy are being evaluated. We aimed to determine the relationship between peanut-specific IgE levels and clinical peanut allergy in peanut-sensitized children and how this was influenced by eczema, asthma and clinical setting (primary or secondary care). We enrolled 280 children (0–18 years) who tested positive for peanut-specific IgE (> 0.35 kU/L) requested by primary and secondary physicians. We used predefined criteria to classify participants into three groups: peanut allergy, no peanut allergy, or possible peanut allergy, based on responses to a validated questionnaire, a detailed food history, and results of oral food challenges.
Fifty-two participants (18.6%) were classified as peanut allergy, 190 (67.9%) as no peanut allergy, and 38 (13.6%) as possible peanut allergy. The association between peanut-specific IgE levels and peanut allergy was significant but weak (OR 1.46 for a 10.0 kU/L increase in peanut-specific IgE, 95% CI 1.28-1.67). Eczema was the strongest risk factor for peanut allergy (aOR 3.33, 95% CI 1.07-10.35), adjusted for demographic and clinical characteristics. Asthma was not significantly related to peanut allergy (aOR 1.93, 95% CI 0.90-4.13). Peanut allergy was less likely in primary than in secondary care participants (OR 0.46, 95% CI 0.25-0.86), at all levels of peanut-specific IgE.
The relationship between peanut-specific IgE and peanut allergy in children is weak, is strongly dependent on eczema, and is weaker in primary compared to secondary care. This limits the usefulness of peanut-specific IgE levels in the diagnosis of peanut allergy in children.
Peanut allergy; Peanut-specific IgE; Peanut sensitization; Eczema; Asthma; Children; Teenagers
Open-label oral immunotherapy (OIT) protocols have been used to treat small numbers of patients with peanut allergy. Peanut OIT has not been evaluated in double-blind, placebo-controlled trials.
To investigate the safety and effectiveness of OIT for peanut allergy in a double blind, placebo-controlled study.
In this multicenter study, peanut-allergic children ages 1-16 years received OIT with peanut flour or placebo. Initial escalation, build-up, and maintenance phases were followed by an oral food challenge at approximately one year. Titrated skin prick tests (SPT) and laboratory studies were performed at regular intervals.
Twenty-eight subjects were enrolled in the study. Three peanut OIT subjects withdrew early in the study due to allergic side effects. During the double-blind, placebo-controlled food challenge, all remaining peanut OIT subjects (N=16) ingested the maximum cumulative dose of 5000 mg (approximately 20 peanuts), while placebo subjects (N=9) ingested a median cumulative dose of 280 mg (range, 0-1900 mg) [p<0.001]. In contrast to the placebo group, the peanut OIT group showed reductions in SPT size (p<0.001), IL-5 (p=0.01), and IL-13 (p=0.02) and increases in peanut-specific IgG4 (p<0.001). Peanut OIT subjects had initial increases in peanut-specific IgE (p<0.01) but did not show significant change from baseline by the time of OFC. The ratio of FoxP3 hi: FoxP3 intermediate CD4+CD25+ T cells increased at the time of OFC (p=0.04) in peanut OIT subjects.
These results conclusively demonstrate that peanut OIT induces desensitization and concurrent immune modulation. The present study continues and is evaluating the hypothesis that peanut OIT causes long-term immune tolerance.
peanut allergy; oral immunotherapy; desensitization; food allergy
History and severity of atopic dermatitis (AD) are risk factors for peanut allergy. Recent evidence suggests that children can become sensitized to food allergens through an impaired skin barrier. Household peanut consumption, which correlates strongly with peanut protein levels in household dust, is a risk factor for peanut allergy.
We sought to assess whether environmental peanut exposure (EPE) is a risk for peanut sensitization and allergy and whether markers of an impaired skin barrier modify this risk.
Peanut protein in household dust (in micrograms per gram) was assessed in highly atopic children (age, 3-15 months) recruited to the Consortium of Food Allergy Research Observational Study. History and severity of AD, peanut sensitization, and likely allergy (peanut-specific IgE, ≥5 kUA/mL) were assessed at recruitment into the Consortium of Food Allergy Research study.
There was an exposure-response relationship between peanut protein levels in household dust and peanut skin prick test (SPT) sensitization and likely allergy. In the final multivariate model an increase in 4 log2 EPE units increased the odds of peanut SPT sensitization (1.71-fold; 95% CI, 1.13- to 2.59-fold; P = .01) and likely peanut allergy (PA; 2.10-fold; 95% CI, 1.20- to 3.67-fold; P < .01). The effect of EPE on peanut SPT sensitization was augmented in children with a history of AD (OR, 1.97; 95% CI, 1.26-3.09; P < .01) and augmented even further in children with a history of severe AD (OR, 2.41; 95% CI, 1.30-4.47; P < .01); the effect of EPE on PA was also augmented in children with a history of AD (OR, 2.34; 95% CI, 1.31-4.18; P < .01).
Exposure to peanut antigen in dust through an impaired skin barrier in atopically inflamed skin is a plausible route for peanut SPT sensitization and PA.
Atopic dermatitis; peanut sensitization; peanut allergy; environmental peanut exposure; dust; AD, Atopic dermatitis; CoFAR, Consortium of Food Allergy Research; EPE, Environmental peanut exposure; FLG, Filaggrin; IQR, Interquartile range; LLQ, Lower limit of quantitation; LR, Logistic regression; OR, Odds ratio; PA, Peanut allergy; sIgE, Specific IgE; SPT, Skin prick test
IgE-mediated peanut allergy is a complex trait with strong heritability, but its genetic basis is currently unknown. Loss-of-function mutations within the filaggrin gene are associated with atopic dermatitis and other atopic diseases; therefore, filaggrin is a candidate gene in the etiology of peanut allergy.
To investigate the association between filaggrin loss-of-function mutations and peanut allergy.
Case-control study of 71 English, Dutch, and Irish oral food challenge–positive patients with peanut allergy and 1000 non peanut-sensitized English population controls. Replication was tested in 390 white Canadian patients with peanut allergy (defined by food challenge, or clinical history and skin prick test wheal to peanut ≥8 mm and/or peanut-specific IgE ≥15 kUL−1) and 891 white Canadian population controls. The most prevalent filaggrin loss-of-function mutations were assayed in each population: R501X and 2282del4 in the Europeans, and R501X, 2282del4, R2447X, and S3247X in the Canadians. The Fisher exact test and logistic regression were used to test for association; covariate analysis controlled for coexistent atopic dermatitis.
Filaggrin loss-of-function mutations showed a strong and significant association with peanut allergy in the food challenge–positive patients (P = 3.0 × 10−6; odds ratio, 5.3; 95% CI, 2.8-10.2), and this association was replicated in the Canadian study (P = 5.4 × 10−5; odds ratio, 1.9; 95% CI, 1.4-2.6). The association of filaggrin mutations with peanut allergy remains significant (P = .0008) after controlling for coexistent atopic dermatitis.
Filaggrin mutations represent a significant risk factor for IgE-mediated peanut allergy, indicating a role for epithelial barrier dysfunction in the pathogenesis of this disease.
Atopic dermatitis; filaggrin; IgE; peanut allergy; risk factor; AD, Atopic dermatitis; ALSPAC, Avon Longitudinal Study of Parents and Children; FLG, Filaggrin; OR, Odds ratio; SPT, Skin prick test; UK, United Kingdom
There are no published data on peanut sensitization in Egypt and the problem of peanut allergy seems underestimated. We sought to screen for peanut sensitization in a group of atopic Egyptian children in relation to their phenotypic manifestations.
We consecutively enrolled 100 allergic children; 2-10 years old (mean 6.5 yr). The study measurements included clinical evaluation for site of allergy, possible precipitating factors, consumption of peanuts (starting age and last consumption), duration of breast feeding, current treatment, and family history of allergy as well as skin prick testing with a commercial peanut extract, and serum peanut specific and total IgE estimation. Children who were found sensitized to peanuts were subjected to an open oral peanut challenge test taking all necessary precautions.
Seven subjects (7%) were sensitized and three out of six of them had positive oral challenge denoting allergy to peanuts. The sensitization rates did not vary significantly with gender, age, family history of allergy, breast feeding duration, clinical form of allergy, serum total IgE, or absolute eosinophil count. All peanut sensitive subjects had skin with or without respiratory allergy.
Peanut allergy does not seem to be rare in atopic children in Egypt. Skin prick and specific IgE testing are effective screening tools to determine candidates for peanut oral challenging. Wider scale multicenter population-based studies are needed to assess the prevalence of peanut allergy and its clinical correlates in our country.
There are no treatments currently available for peanut allergy. Sublingual immunotherapy is a novel approach to the treatment of peanut allergy.
To investigate the safety, clinical effectiveness and immunologic changes with sublingual immunotherapy in peanut-allergic children.
In this double-blind, placebo-controlled study, subjects underwent 6 months of dose escalation and 6 months of maintenance dosing followed by a double-blind, placebo-controlled food challenge.
Eighteen children ages 1 to 11 years completed 12 months of dosing and the food challenge. Dosing side effects were primarily oropharyngeal and uncommonly required treatment. During the double-blind, placebo-controlled food challenge, the treatment group safely ingested 20 times more peanut protein than the placebo group (median 1710 mg vs. 85 mg, p=0.011). Mechanistic studies demonstrated a decrease in prick skin test wheal size (p=0.020) and decreased basophil responsiveness after stimulation with 10−2 mcg/ml (p=0.009) and 10−3 mcg/ml (p=0.009) of peanut. Peanut-specific IgE increased over the initial 4 months (p=0.002) then steadily decreased over the remaining 8 months (p=0.003) while peanut-specific IgG4 increased during the 12 months (p=0.014). Lastly, IL-5 levels decreased after 12 months (p=0.015). No statistically significant changes were found in IL-13 levels, the percent of T regulatory cells, or IL-10 and IFN-gamma production.
Peanut sublingual immunotherapy is able to safely induce clinical desensitization in peanut allergic children with evidence of immunologic changes suggesting a significant change in the allergic response. Further study is required to determine if continued peanut sublingual immunotherapy is able to induce long-term immune tolerance.
peanut allergy; sublingual immunotherapy; desensitization; food allergy
OBJECTIVE--To investigate clinical features of acute allergic reactions to peanuts and other nuts. DESIGN--Analysis of data from consecutive patients seen by one doctor over one year in an allergy clinic at a regional referral centre. SUBJECTS--62 patients aged 11 months to 53 years seen between October 1993 and September 1994. MAIN OUTCOME MEASURES--Type and severity of allergic reactions, age at onset of symptoms, type of nut causing allergy, results of skin prick tests, and incidence of other allergic diseases and associated allergies. RESULTS--Peanuts were the commonest cause of allergy (47) followed by Brazil nut (18), almond (14), and hazelnut (13). Onset of allergic symptoms occurred by the age of 2 years in 33/60 and by the age of 7 in 55/60. Peanuts accounted for all allergies in children sensitised in the first year of life and for 82% (27/33) of allergies in children sensitised by the third year of life. Multiple allergies appeared progressively with age. The commonest symptom was facial angioedema, and the major feature accounting for life threatening reactions was laryngeal oedema. Hypotension was uncommon. Of 55 patients, 53 were atopic--that is, had positive skin results of tests to common inhaled allergens--and all 53 had other allergic disorders (asthma, rhinitis, eczema) due to several inhaled allergens and other foods. CONCLUSIONS--Sensitisation, mainly to peanuts, is occurring in very young children, and multiple peanut/nut allergies appear progressively. Peanut and nut allergy is becoming common and can cause life threatening reactions. The main danger is laryngeal oedema. Young atopic children should avoid peanuts and nuts to prevent the development of this allergy.
Allergy to lentils is infrequent in Latin America: this a first case report from Venezuela. A 5 year old female preschooler attended our allergology clinic with chief complaint of generalized giant urticaria inmediately after ingestion of cooked lentils; clinical history revealed frequent (>3) emergency visits, since the age of one year, with facial angioedema and generalized urticaria even from inhalation of vapors while cooking of lentils at home; moreover, also symptoms described ocurred while eating foods containing chick peas; lentils, as other beans (black, red, chick), belong to the leguminosa family along with peanuts and coconut.
Prick lancetter skin tests (H-S) to a panel of 25 inhalant and food allergens (Diater Labs, Argentina) were performed along with Prick to Prick tests to raw and cooked lentils, chickpeas, black beans, navy beans and coconut. A papule >3 mm and read at 10 minutes was considered positive.
All other allergens tested were negative, that is, epithelia, molds, cockroach, grasses, mosquito, milk, egg, wheat, fishmix, shrimp and other seafood, nuts, hazelnut, almond, coconut and blackbeans.
1. Prick to Prick testing confirms specific IgE presence to Lentils; our patient could tolerate peanuts and cocunut. Positive prick test to peanuts likely represent a cross reaction1; 2. Lupin flour (Lupinus Albus), from the Leguminosa family, is found increasingly used in industrially prepared foods and could elicit symptoms due to cross reactions, and advice to family was given accordingly2; 3. This is the first case report from Venezuela.
Immune features of infants with food allergy have not been delineated.
To explore basic mechanisms responsible for food allergy and identify biomarkers, e.g. prick skin tests (PST), food-specific IgE, and mononuclear cell responses in a cohort of infants with likely milk/egg allergy at increased risk of developing peanut allergy.
Infants aged 3–15 months were enrolled with a positive PST to milk or egg and either a corresponding convincing clinical history of allergy to milk or egg, or with moderate to severe atopic dermatitis (AD). Infants with known peanut allergy were excluded.
Overall, 512 infants (67% males) were studied with 308 (60%) having a history of a clinical reaction. Skin tests and/or detectable food-specific IgE revealed sensitization as follows: milk-78%, egg-89% and peanut-69%. PST and food-specific IgE levels were discrepant for peanut: 15% IgE ≥ 0.35 kUA/L/PST- versus 8% PST+/IgE < 0.35, p = 0.001. Mononuclear cell allergen stimulation screening for CD25, CISH, FOXP3, GATA3, IL-10, IL-4, IFN-gamma and TBET expression using casein, egg white and peanut revealed that only allergen-induced IL-4 expression was significantly increased in those with clinical allergy to milk (compared to non-allergic) and in those sensitized to peanut, despite the absence of an increase in GATA-3 mRNA expression.
Infants with likely milk/egg allergy are at considerably high risk of having elevated peanut-specific IgE (potential allergy). Peanut-specific serum IgE was a more sensitive indicator of sensitization than PST. Allergen-specific IL-4 expression may be a marker of allergic risk. Absence of an increase in GATA-3 mRNA expression suggests that allergen-specific IL-4 may not be of T cell origin.
food allergy; sensitization; atopy
Sesame and coconut are emerging food allergens in the US. We sought to examine whether children allergic to peanuts and tree nuts are at increased risk of having an allergy to sesame or coconut. We performed a retrospective chart review of children who underwent skin prick testing (SPT) to sesame and coconut and identified 191 children who underwent SPT to sesame and 40 to coconut. Sensitization to sesame was more likely in children with positive SPT to peanuts (odds ratio [OR] = 6.7, 95% confidence interval [CI] [2.7–16.8], P<0.001) and tree nuts (OR = 10.5, 95% CI [4.0–27.7], P<0.001). Children with histories of both peanut and tree nut reaction were more likely to have a history of sesame reaction (OR = 10.2, 95% CI [2.7–38.7], P<0.001). Children with sensitization or allergy to peanuts or tree nuts were not more likely to be sensitized or allergic to coconut. In conclusion, children with peanut or tree nut sensitization were more likely to be sensitized to sesame but not coconut. Children with clinical histories of both peanut and tree nut allergy were more likely to be allergic to sesame.
sesame; coconut; peanut; tree nut; skin prick test; food allergy
The botanical relation between grass and cereal grains may be relevant when diagnosing food allergy to cereals. The aim was to investigate the diagnostic specificity of skin prick test (SPT) and specific immunoglobulin E (sIgE) tests to cereals and peanut in grass pollen allergic subjects without history of, and clinically reactions to foods botanically related to grass.
70 subjects (41 females; mean age 32 years) and 20 healthy controls (13 females; mean age 24 years) were tested by open food challenge (OFC) with cereals and peanut. SPT and sIgE both with Immulite® (Siemens) and ImmunoCAP® (Phadia) to grass and birch pollen, cereals, peanut and bromelain were performed.
Of the 65 OFC-negative subjects 29-46% (SPT, depending on cut-off), 20% (Immulite) and 38% (ImmunoCAP) had positive results to one or more of the foods tested. Controls were negative in all tests. Cross-reactive carbohydrate determinants (CCD) as evidenced by reaction to bromelain could explain only a minority of the measured IgE-sensitizations.
Grass pollen allergic patients with documented food tolerance to cereals and peanut may express significant sensitization. False-positive cereal or peanut allergy diagnoses may be a quantitatively important problem both in routine clinical work and epidemiological studies.
Cereals; cross-reaction; diagnosis; food challenge; grass pollen allergy
It 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.
A 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.
A 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.
Sunflower seed; Allergy; Risk factors
Food-allergy is a substantial and evolving health issue. We evaluate the frequency of food sensitization by prick-to-prick and atopy patch test (APT) in allergic children in a tertiary pediatric care center.
Cross-sectional retrospective study of prick-to-prick and APT tests made in atopic children attending to the Pediatric Allergy and Clinical Immunology outpatient clinic aged 6 months to 19 years. Patients were stratified in 4 groups according to age (<1, 1–5, 6–10 and >11 years), and by atopy-related diagnosis (asthma, rhinitis, food allergy, atopic dermatitis and eosinophilic gastroenteropathy).
Total of 170 prick-to-prick with fresh foods were made, 135 were positive with the next distribution: milk 28.8%, (95% CI, 21.3-36.3%), egg white 20.1% (95% CI, 13.5-26.8%), banana 19.4% (95% CI, 12.8-26%). Sensitization to milk was most common in children aged 1 to 5 years old with 26.9% (95% CI, 17.1-36.8%) compared with corn, nuts and peanuts P < 0.05. Sensitization to milk was the most frequent in the food allergy diagnosis group with 27.1% (95% CI,15.8-38.5%) compared with wheat, corn and peanuts P < 0.05.
A total of 140 APT tests were made, 105 were positive with the next distribution: soybeans 53.3% (95% CI,43.8-62.8%), peanut and chocolate both with 50.5% (95% CI,40.9-60,.0). This finding was sustained in patients with atopic dermatitis with soybean 55.6% (95% CI,36.8-74.3) compared to egg yolk. Sensitization to soybeans was most common in children aged 1 to 5 years old with 52.1% (95% CI,40.6-63.6) compared to rice and egg yolk P < 0.05. A different distribution was found for the 6 to 10 years old aged group: peanut 41.9% (95% CI,27.1-56.6) compared with egg yolk P < 0.05.
Milk is the most common food-allergen found by prick-to-prick in children independent of age or allergic diagnosis, with statistical significant difference, when compared to other food-allergens, in the group of food-allergy diagnosis and in the 1 to 5 years old age-group. Soybean is the most common food-allergen found in atopy patch test in the groups <1, 1 to 5 and >11 years old, independent of atopy related diagnosis, with statistical significant difference, when compared to other food-allergens in the group of atopic dermatitis and in the 1 to 5 years old age-group. For the 6 to 10 years old group peanut was the most common food-allergen found by APT, independent of atopy related diagnosis
IgE-mediated food allergy is a transient condition for some children, however there are few indices to predict when and in whom food allergy will resolve. Skin prick test (SPT) and serum-specific IgE levels (sIgE) are usually monitored in the management of food allergy and are used to predict the development of tolerance or persistence of food allergy. The aim of this article is to review the published literature that investigated the predictive value of SPT and sIgE in development of tolerance in children with a previous diagnosis of peanut, egg and milk allergy. A systematic search identified twenty-six studies, of which most reported SPT or sIgE thresholds which predicted persistent or resolved allergy. However, results were inconsistent between studies. Previous research was hampered by several limitations including the absence of gold standard test to diagnose food allergy or tolerance, biased samples in retrospective audits and lack of systematic protocols for triggering re-challenges. There is a need for population-based, prospective studies that use the gold standard oral food challenge (OFC) to diagnose food allergy at baseline and follow-up to develop SPT and sIgE thresholds that predict the course of food allergy.
food allergy; natural history; tolerance; skin prick test; serum-specific immunoglobulin E; hen’s egg; peanut; cow’s milk
Children with food-specific IgE (FSIgE) ≤2 kUa/L to milk, egg, or peanut (or ≤5kUa/L to peanut without history of previous reaction) are appropriate candidates for oral food challenge (OFC) to investigate resolution of food allergy, because these FSIgE cutoffs are associated with ∼50% likelihood of negative OFC. This study was designed to identify characteristics of children undergoing OFC, based on these FSIgE levels, who are most likely to show negative OFC. We collected demographics, severity of previous reaction, history of atopic diseases, total IgE and FSIgE values, and skin tests results on children who underwent OFCs to milk, egg, or peanut, based on the recommended FSIgE cutoffs. We identified independent factors associated with negative OFCs. Four hundred forty-four OFCs met our inclusion criteria. The proportions of negative OFCs performed based on FSIgE cutoffs alone were 58, 42, and 63% to milk, egg, and peanuts, respectively. Regression models identified independent factors associated with negative OFCs: lower FSIgE levels (all three foods), higher total IgE (milk), consumption of baked egg products (egg), and non-Caucasian race (eggs and peanuts). Combinations of these factors identified subgroups of children with proportions of negative OFCs of 83, 75, and 75% for milk, eggs, and peanuts, respectively. Combinations of clinical and laboratory elements, together with FSIgE values, might identify more children who are likely to have negative OFCs compared with current recommendations using FSIgE values alone. Once validated in a different population, these factors might be used for selection of patients who are most likely to show negative OFCs.
Children; food allergy; food specific IgE; oral food challenge; regression models; skin test; total IgE
The objective of this study was to determine the risk of peanut allergy in siblings of peanut-allergic children. In 2005-2006, 560 households of children born in 1995 in the province of Manitoba, Canada, were surveyed. The index children (8-to 10-year-olds) were assessed by a pediatric allergist and had skin-prick testing and/or capRAST for peanut allergy. Surveys were completed by parents for siblings to determine the presence of peanut allergy. Of 560 surveys, 514 (92%) were completed. Twenty-nine (5.6%) index children were peanut allergic. Fifteen of 900 (1.7%) siblings had peanut allergy. Four of 47 (8.5%) were siblings of peanut-allergic children and 11 of 853 (1.3%) were siblings of non-peanut-allergic children. The risk of peanut allergy was markedly increased in siblings of a peanut-allergic child (odds ratio 6.72, 95% confidence interval 2.04-22.12). Siblings of peanut-allergic children are much more likely to be allergic to peanut. An allergy assessment by a qualified allergist should be routinely recommended before feeding peanut to these children.
allergy tests; cohort study; odds ratio; peanut allergy; siblings
Peanut allergy is relatively common, typically permanent, and often severe. Double-blind, placebo-controlled food challenge is considered the gold standard for the diagnosis of food allergy–related disorders. However, the complexity and potential of double-blind, placebo-controlled food challenge to cause life-threatening allergic reactions affects its clinical application. A laboratory test that could accurately diagnose symptomatic peanut allergy would greatly facilitate clinical practice.
We sought to develop an allergy diagnostic method that could correctly predict symptomatic peanut allergy by using peptide microarray immunoassays and bioinformatic methods.
Microarray immunoassays were performed by using the sera from 62 patients (31 with symptomatic peanut allergy and 31 who had outgrown their peanut allergy or were sensitized but were clinically tolerant to peanut). Specific IgE and IgG4 binding to 419 overlapping peptides (15 mers, 3 offset) covering the amino acid sequences of Ara h 1, Ara h 2, and Ara h 3 were measured by using a peptide microarray immunoassay. Bioinformatic methods were applied for data analysis.
Individuals with peanut allergy showed significantly greater IgE binding and broader epitope diversity than did peanut-tolerant individuals. No significant difference in IgG4 binding was found between groups. By using machine learning methods, 4 peptide biomarkers were identified and prediction models that can predict the outcome of double-blind, placebo-controlled food challenges with high accuracy were developed by using a combination of the biomarkers.
In this study, we developed a novel diagnostic approach that can predict peanut allergy with high accuracy by combining the results of a peptide microarray immunoassay and bioinformatic methods. Further studies are needed to validate the efficacy of this assay in clinical practice.
Epitope mapping; peptide microarray; peanut allergy; bioinformatics; machine learning; allergy diagnosis; epitope biomarker
Food-induced allergic reactions are responsible for a variety of symptoms and disorders involving the skin, gastrointestinal and respiratory tracts and can be attributed to IgE-mediated and non–IgE-mediated (cellular) mechanisms.
Food allergy frequency varies according to age, local diet, and many other factors. The diagnosis of food allergy is based on clinical history, skin prick test (SPT), food specific IgE and more recently atopy patch tests (APT). If needed the use of an oral food challenge to confirm allergy or tolerance.
Describes the case of a patient with multiple manifestations of food allergy after eating habit change.
Man 20 years with a history of food allergy to egg in childhood (at date in remission) asthma and rhinitis and urticaria in contact to cats. He presents an atopic dermatitis, recurrent abdominal pain and diarrhea 18 months after change in eating habits (he became vegetarian). He also presents oral syndrome with cow's milk. The patient had 4 episodes of anaphylaxis post prandial grade 3. In 3 of them the patient ate goat cheese and the other cow cheese. Also 2 of the episodes were associated with exercise. Skin prick tests with goat`s cheese: 13 mm, cow´s milk: 8 mm wheat: 3 mm, corn 3 mm, chicken 3.5 mm, egg yolk: 3.5 mm, avocado and rice 3 mm. Atopy patch test: (+ +) goat`s milk (+) peanuts and coffee. Total IgE 686 IU/mL.
Foods with positive results were excluded from the diet and a complete remission of atopic dermatitis, abdominal pain, diarrhea and anaphylaxis was observed. All foods were reintroduced successfully except milk of goats and cows milk. The patient is currently asymptomatic.
The literature describes different kinds of manifestations of food allergy: immediate hypersensitivity (IgE mediated), delayed hypersensitivity (T lymphocytes mediated) and mixed. Highlights in this case an adult patient with a history of atopy who makes changes in eating habits, developping a food allergy to goat´s and cow s milk, with immediate (anaphylaxis, oral syndrome) and delayed manifestations (atopic dermatitis and chronic diarrhea).
The prevalence of peanut allergy in Korea is lower than in America. Peanut extract allergens between the two countries have not been standardized. This study was performed to compare the allergenicity of raw Korean and American peanuts with that of roasted peanuts. We prepared the peanut extracts in Korean raw (KP) and roasted peanuts (KRP), and also in American raw (AP) and roasted (ARP) peanuts. We compared the peanut extract allergens of KP, KRP, AP and ARP in vitro with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by immunoblotting, T-cell proliferation assay and skin prick test with sera from peanut-allergic patients. SDS-PAGE and Western blotting demonstrated four allergenic extracts, numerous bands that displayed a high prevalence of IgE binding. IgE-binding bands were at 64, 36 and 17 kDa. Western blot inhibition revealed that either KP or AP could almost completely inhibit the reactivity of the other extract. There were no differences between T-cell proliferation assay and skin prick test. In conclusion, this investigation showed no different allergic components in both raw and roast extracts of Korean and American peanuts.