Food allergy and food sensitization in early childhood: results from the DARC cohort

Background: The prevalence of food hypersensitivity (FHS) and the relationship with atopic dermatitis (AD) is controversial. The aim of this study was to determine the development of FHS and to correlate this with AD in relation to sensitization and symptoms. Methods: This study combines new data from birth to 18 months of age with previous published results from 3 and 6 years. The Danish Allergy Research Centre cohort, including 562 children, is a unique, population‐based, prospective birth cohort, with clinical examinations at all follow‐ups. All children were examined for the development of AD using Hanifin‐Rajka criteria and for FHS using interviews, skin prick test (SPT), specific immunoglobulin E (IgE), and food challenge according to EAACI guidelines. Results: Twenty children were confirmed with FHS to milk, egg, and peanut. FHS peaked at 18 months (3.6%) and then decreased to 1.2% at 72 months of age. No new cases were found after 3 years. Self‐reporting could only be confirmed in 31% of cases. Among the 122 children with AD, 18 had FHS (14.8%). FHS was IgE‐mediated in 95% of the cases but 16 of 20 children were additionally sensitized to other foods which they tolerated. Children with AD were neither more IgE‐sensitized nor had higher levels of IgE when compared with healthy children but they were more persistently sensitized. Conclusions: Sensitization to foods in young children without food allergy seems to be a normal phenomenon. The discrepancy between sensitization, self‐reported food‐related symptoms and confirmed FHS illustrates the need to perform standardized oral challenges in order to confirm the diagnosis of FHS.     

Familial aggregation of food allergy and sensitization to food allergens: a family-based study

Background The increasing prevalence of food allergy (FA) is a growing clinical and public health problem. The contribution of genetic factors to FA remains largely unknown. Objective This study examined the pattern of familial aggregation and the degree to which genetic factors contribute to FA and sensitization to food allergens. Methods This study included 581 nuclear families (2,004 subjects) as part of an ongoing FA study in Chicago, IL, USA. FA was defined by a set of criteria including timing, clinical symptoms obtained via standardized questionnaire interview and corroborative specific IgE cut‐offs for 95% positive predictive value (PPV) for food allergens measured by Phadia ImmunoCAP. Familial aggregation of FA as well as sensitization to food allergens was examined using generalized estimating equation (GEE) models, with adjustment for important covariates including age, gender, ethnicity and birth order. Heritability was estimated for food‐specific IgE measurements. Results FA in the index child was a significant and independent predictor of FA in other siblings (OR=2.6, 95% CI: 1.2–5.6, P=0.01). There were significant and positive associations among family members (father–offspring, mother–offspring, index–other siblings) for total IgE and specific IgE to all the nine major food allergens tested in this sample (sesame, peanut, wheat, milk, egg white, soy, walnut, shrimp and cod fish). The estimated heritability of food‐specific IgE ranged from 0.15 to 0.35 and was statistically significant for all the nine tested food allergens. Conclusion This family‐based study demonstrates strong familial aggregation of FA and sensitization to food allergens, especially, among siblings. The heritability estimates indicate that food‐specific IgE is likely influenced by both genetic and environmental factors. Together, this study provides strong evidence that both host genetic susceptibility and environmental factors determine the complex trait of IgE‐mediated FA.     

Confirmation of the association between high levels of immunoglobulin E food sensitization and eczema in infancy: an international study

Background Studies of Australian infants have reported that more than 80% of those with moderate atopic eczema (AE) have high levels of IgE food sensitization (IgE‐FS) that are commonly associated with IgE food allergy. Objectives To explore the relationship between high levels of IgE‐FS and AE in a large cohort of young children with eczema participating in a multi‐centre, international study. Methods Two thousand one hundred and eighty‐four subjects (mean age 17.6 months, range 11.8–25.4; 1246 males) with active eczema from atopic families from 94 centres in 12 countries were studied. Clinical history, Scoring Atopic Dermatitis index as a measure of eczema severity and CAP‐FEIA measurements for total IgE and IgE antibody levels to cow milk, egg and peanut were entered into a database. If CAP‐FEIA levels exceeded previously reported age‐specific cut‐off levels for 95% positive predictive values (PPVs) for food allergy, subjects were defined as having high‐risk IgE‐FS (HR‐IgE‐FS). Results Serum was available from 2048 patients; 55.5% were atopic. The frequency of HR‐IgE‐FS to milk, egg and/or peanut was the greatest in patients whose eczema developed in the first 3 months of life and the least in those whose eczema developed after 12 months (P<0.0001). In a regression analysis to allow for potential confounding factors, children with HR‐IgE‐FS had the most severe eczema and the youngest age of onset (P<0.001); 64% of infants with severe eczema of onset‐age <3 months had HR‐IgE‐FS. Conclusion Early‐onset severe eczema in infancy was associated with HR‐IgE‐FS. Clinical implications Food allergies should be routinely assessed in infants with moderate or severe eczema. Capsule summary In eczematous infants, the earlier the age of onset, and the greater the severity of eczema, the greater the frequency of associated high levels of IgE‐FS.     

IgE in stools as indicator of food sensitization

The fragment of the Fc segment of IgE resistant to proteolytic enzymes was determined by a radioimmunologic method in fecal extracts from several groups of patients. IgEs remained undetectable in the 95 healthy subjects studied. IgEs were detected in 16/27 carriers of intestinal parasites (60%), with a mean of 92.4 IU/g dry weight. IgEs were also detected in 236/312 food-sensitization patients, with the sensitizing foodstuffs being identified by searching for the specific IgEs in circulation (75%), with a mean of 63.9 IU/g dry weight. The simultaneous determination of alpha- 1-antitrypsin in fecal extracts arid in sera from 21 control subjects and 21 food-sensitization carriers demonstrated that extravasation of plasma proteins into the gut lumen cannot be responsible for the presence of IgE in stools. Testing for IgE in stools therefore appears to be a simple and economical means of identifying patients without parasites who present with food sensitization.     

Prospective study of laboratory-animal allergy: factors predisposing to sensitization and development of allergic symptoms

In a prospective study of laboratory technicians, selected indicators of allergy and atopy were studied in an attempt to determine predictors of laboratory-animal allergy (LAA). Laboratory technicians underwent spirometry, methacholine provocation tests, and blood sampling, and responded to a questionnaire during training and after 2 years' work. Among 38 laboratory-animal-exposed subjects, total IgE before exposure gave the best correlation ( P < 0.01; Mann-Whitney U-test) to reported symptoms caused by laboratory animals ( n = 8) at follow-up. The prevalence of atopy and allergic symptoms had increased in exposed technicians at follow-up, but this was also found among unexposed matched referents ( n = 36 pairs). One subject in the exposed group reported asthma before exposure, compared with seven at follow-up ( P < 0.05; Fisher's exact test). However, the prevalence of asthma had increased from two to six (not significant) also among unexposed technicians. There were no significant differences between the groups in any measured variable at follow-up. Among 43 subjects who later worked with laboratory animals, 21%, had a positive skin prick test for common allergens, as compared with 37% among 112 without animal exposure P = 0.06; x² test), suggesting selection for laboratory animal work.     

Sensitization to inhalant allergens between 4 and 8 years of age is a dynamic process: results from the BAMSE birth cohort

Background There is limited knowledge of the development of IgE-antibody levels over time in childhood, with respect to persistency and co-sensitization to specific inhalant allergens.
Methods Data from 2033 children participating in the BAMSE birth cohort was used. Background factors and clinical parameters were obtained and IgE antibody (ab) levels to eight common airborne allergens were measured (0.35 kU_A/L) when the children were 4 and 8 years of age.
Results Between 4 and 8 years the proportion of children sensitized to any of the inhalant allergens tested increased from 15% to 25%. At 4 years IgE-ab to birch and cat dominated, whereas at the age of 8, there was a considerable increase in the proportion of sensitization to timothy and dog. Except for mites and moulds, IgE-ab levels to all aeroallergens increased significantly between 4 and 8 years among those already sensitized at 4. Transient sensitization to inhalant allergen was uncommon. Furthermore, sensitization to birch pollen at 4 years increased the risk for becoming sensitized to timothy, cat and dog later in life. Such an association was not observed among those sensitized primarily to animal dander.
Conclusions There is a prominent process of sensitization at pre-school age to inhalant allergens, and in Northern Europe sensitization to birch pollen early in life seems to be important for this process. Such a process has a probable impact on the development of allergic disease in the growing child.     

Diagnostic pitfalls in food allergy in children

Currently, the diagnostic work-up of suspected food allergy includes skin prick tests, the measurement of food specific immunoglobulin E (IgE), and the atopy patch test, and double-blind, placebo-controlled food challenges. However, all of these methods, even double-blind, placebo-controlled food challenges (DBPCFC), may sometimes be misleading. This overview describes several pitfalls for standard diagnostic methods such as problems with irritative skin reactions mimicking IgE-mediated symptoms, the problem of non-IgE-mediated reactions, pitfalls arising from the way foods are prepared or processed, effects of the route of exposure, the role of augmentation factors lowering the threshold value for clinical reactions, the noncomparability of specific IgE decision points, the influence of the timing of diagnostic measures. In addition, the problem of alternative diagnostic measures is discussed. In conclusion, there are several pitfalls in the diagnostic work-up of food allergy, which may be misleading for the physician. Properly performed controlled oral food challenges still represent the gold standard for implementing specific diets in food allergic individuals in order to avoid both unjustified diets, which may lead to severe impairments in growth and development, and to avoid unnecessary symptoms if an underlying food allergy is not correctly identified as a cause for the symptoms of the patient.     

Comparative evaluation between two immunoenzymatic techniques (FAST and Phadezym) and the Phadebas RAST in food allergy

The diagnosis of food IgE-dependent hypersensitivity is based on the demonstration of specific IgE, completed by provocation tests. Two immunoenzymatic techniques, the Phadezym and the FAST, are compared with the Phadebas RAST, in 86 sera (23 controls, 28 from patients with a reported food allergy and 35 with a positive RAST to a food allergen). The within-run variation coefficient of class 0-2 sera was 9% for the Phadebas RAST, and higher than 20% for the Phadezym and the FAST. It was in order of 8.7%, 9.4% and of 17.6% respectively for Phadebas RAST, Phadezym and FAST when estimated with class 3-4 sera. The specificity was higher than 95% for the three techniques. The sensitivity was 75% for Phadebas and 43% for Phadezym and FAST. The FAST test is much less sensitive with allergens of vegetal origin than those of animal origin (P less than 0.01). This work indicates the high percentage of false negative results of immunoenzymatic techniques when food extracts are tested. This could be explained either by an enzyme-substrate reaction or by a non-specific inhibition of the enzyme linked to the anti-IgE IgG.     

Interpreting IgE sensitization tests in food allergy

Food allergies are increasing in prevalence, and with it, IgE testing to foods is becoming more commonplace. Food-specific IgE tests, including serum assays and prick skin tests, are sensitive for detecting the presence of food-specific IgE (sensitization), but specificity for predicting clinical allergy is limited. Therefore, positive tests are generally not, in isolation, diagnostic of clinical disease. However, rationale test selection and interpretation, based on clinical history and understanding of food allergy epidemiology and pathophysiology, makes these tests invaluable. Additionally, there exist highly predictive test cutoff values for common allergens in atopic children. Newer testing methodologies, such as component resolved diagnostics, are promising for increasing the utility of testing. This review highlights the use of IgE serum tests in the diagnosis of food allergy.     

Specific oral tolerance induction in food allergy in children: efficacy and clinical patterns of reaction

BACKGROUND: Specific oral tolerance induction (SOTI) seems to be a promising treatment of food allergy. Specific oral tolerance induction and elimination diet were compared with respect to efficacy rate and patterns of clinical reaction. METHODS: Children with challenge proven immunoglobulin E (IgE)-mediated cow's milk (CM) allergy or hen's egg (HE) allergy were randomly assigned to SOTI or elimination diet as a control group. Specific oral tolerance induction treatment was performed at home on a daily basis according to a study protocol with fresh CM or lyophilized HE protein. Re-evaluation of clinically relevant food allergy was performed by food challenge after a median of 21 months. Children in the SOTI group received a secondary elimination diet for 2 months prior to follow-up challenge to evaluate persistence of induced oral tolerance. RESULTS: At follow-up challenge, nine of 25 children (36%) showed permanent tolerance in the SOTI group, three of 25 (12%) were tolerant with regular intake and four of 25 (16%) were partial responders. In the control group, seven of 20 children (35%) were tolerant. Allergen-specific immunoglobulin E decreased significantly both in children who developed natural tolerance during the elimination diet (P < 0.05) and in those with SOTI (P < 0.001). CONCLUSIONS: Specific oral tolerance induction seems a valid treatment option for patients with persistent food allergy. Indications may be given if avoidance cannot be guaranteed or for those who are eager to eat the food in question. Advantages of SOTI are the increased threshold dose for allergic reactions and the substantially reduced risk of severe allergic reactions after inadvertent ingestion of the allergen. However, careful monitoring during SOTI is mandatory.     

Temporal trends of aeroallergen sensitization over twenty-five years

BACKGROUND: Little is known about time trends of allergic respiratory disease in adults, in particular in older adults. Furthermore, few trend studies have used objective measurements of IgE sensitization against inhalant allergens. OBJECTIVES: To investigate time trends of aeroallergen sensitization in adults over a 25-year period. METHODS: The study includes a total of 7820 persons, aged 30, 40, 50, and 60 years, who participated in three repeated cross-sectional studies of the general population of Copenhagen, Denmark, in 1976-1977, 1982-1984, and 1999-2001, respectively. Respiratory allergy was assessed by determination of specific IgE aeroallergen sensitization in stored serum samples. RESULTS: Over this 25-year period, a marked and statistically significant increase in the prevalence of aeroallergen sensitization had occurred. This increase was seen in all age-groups challenging the notion that the allergy epidemic only affects generations born 1960 onwards. For example, in 40-year-olds the prevalence (with 95% confidence intervals) of aeroallergen sensitization was 14.9% (12.7-17.1), 19.7% (17.1-22.3), and 27.6% (25.1-30.1) in 1976-1977, 1982-1984, and 1999-2001, respectively. CONCLUSIONS: Our results support that the allergy epidemic has spread to older adults resulting in a continuing increase in the overall prevalence of aeroallergen sensitization and an increase in the mean age of allergic patients.