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Background: Correct diagnosis of immunoglobulin E (IgE)-mediated disease is the prerequisite for secondary allergy prevention during early childhood.
Objective: To evaluate the diagnostic efficacy of a new blood test, Phadiatop® Infant, in detecting IgE sensitisation to food and inhalant allergens among children at 2 years of age.
Methods: Children (n = 239) were followed prospectively from birth to 2 years of age for the presence of IgE sensitisation and the development of atopic manifestations. Immunoglobulin E sensitisation was evaluated by skin prick test (SPT) and analysis of allergen-specific IgE antibodies in plasma to food and inhalant allergens. The children were classified into three groups: IgE-sensitised, non-IgE sensitised and inconclusive, depending on SPT and allergen-specific IgE results.
Results: Twenty-six (11%) of the children were classified as IgE-sensitised, 182 (76%) as non-IgE sensitised and 31 (13%) as inconclusive. Phadiatop Infant was positive in 50 (21%) of the children. Ten children (4%) with identified IgE antibodies against the selected food and inhalant allergens showed negative Phadiatop Infant. Three children showed positive Phadiatop Infant but were negative in the other tests performed. These results correspond to positive and negative predictive values for Phadiatop Infant of 89 and 99%, respectively. Children with clinical symptoms of atopic diseases had significantly increased levels for Phadiatop Infant (P < 0.01).
Conclusion: Phadiatop Infant appears to be a reliable alternative to SPT and the measurement of allergen-specific IgE antibodies in plasma for detecting clinically important IgE sensitisation among children at 2 years of age.
Allergic disease has become a common reason for paediatric consultations in Western industrialized countries as the prevalence of allergic disease have increased markedly in these countries over the last decades (1). The reasons for this increase are still largely unknown, but it is evident that the development and expression of allergic disease are due to a combination of genetic and environmental factors (2, 3). Although several studies have shown this change in the prevalence of immunoglobulin E (IgE)-mediated diseases, it has been argued that greater awareness and an improved ability to diagnose atopic disease may account, at least in part, for this increase (4).
In early childhood, allergic reactions are often mediated via the development of IgE antibodies. Atopic dermatitis, gastrointestinal symptoms and recurrent wheezing dominate as diseases of possible allergic nature. Immunoglobulin E antibodies to food allergens are most frequent during the first 2–3 years of life, while IgE antibodies to inhalant allergens predominate later in life (2, 5). Allergic reactions to foods, mainly cow's milk and hen's egg, are therefore most common during the first years of life, whereas allergy to inhalant allergens occurs later in life (5–7). Low levels of allergen-specific IgE antibodies to food allergens are a common phenomenon during early childhood and may have no clinical importance (5, 6). However, the presence of IgE antibodies against hen's egg during early infancy has been shown to predict respiratory allergy (7). Furthermore, the prognosis for children with wheezing and positive in vitro and/or in vivo test results for IgE is poorer than for wheezing children with negative test results (8).
Correct diagnosis is the prerequisite for a proper understanding of the allergic disease (9–13). Such diagnosis is of great importance for the child and the family, enabling individualized appropriate treatment and recommendations and avoiding unnecessary concern.
Phadiatop Infant is a new blood test for the detection of IgE antibodies against common food and inhalant allergens among small children (14). The aim of this study was to evaluate the result of the determination of Phadiatop Infant in children in relation to IgE sensitisation and the development of symptoms of atopic disease during the first 2 years of life.
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- Material and methods
Interest is increasing in testing children for allergies. The paediatric section of the European Academy of Allergology and Clinical Immunology (EAACI) has recently published a position paper aiming at stimulating allergy testing within paediatric allergology (9, 18). Recent studies have shown that the measurement of allergen-specific IgE antibodies can also be useful in early childhood (19, 20). Apart from measurements of IgE antibodies and allergen challenges there are no effective tools in the diagnosis of IgE-mediated allergic diseases (21). In this study we have evaluated the usefulness of Phadiatop Infant, a new blood test for the detection of IgE antibodies to food and inhalant allergens, among children at 2 years of age. The efficacy of Phadiatop Infant in differentiating children with and without IgE sensitisation was highly significant.
Quantitative measurements of IgE antibodies as a tool for more precise allergy testing are presently under investigation (19, 20). The present study gave a further opportunity to evaluate the quantitative capacity of Phadiatop Infant in young children. Thus, children with allergen-specific IgE antibodies in plasma and a positive SPT, as well as children with clinical manifestations of atopic disease, showed increased values for Phadiatop Infant compared to nonsensitised children and symptom-free children.
A logistic regression model was established associating the quantitative levels for Phadiatop Infant with the classification (IgE sensitisation) assessed in terms of individual allergens in plasma and SPT. It showed a probability of 90% for classification as IgE-sensitised if Phadiatop Infant had an IgE antibody concentration of at least 0.7 PAU/l. However, it should be emphasized that this analysis was performed on a selected and rather small group of children using IgE sensitisation as the decision criterion. Further studies are needed before our results can be generalized to the whole population.
Fifty-seven (24%) children in our study were sensitised against the selected allergens, but only 26 (46%) of these children showed both a positive SPT and the presence of allergen-specific IgE antibodies in plasma. As expected, IgE sensitisation to food allergens dominated over IgE sensitisation to inhalant allergens (22, 23). Phadiatop Infant detected all but ten of the cases of IgE sensitisation. In six of these ten cases Phadiatop Infant did not detect IgE sensitisation to cow's milk. This may indicate that Phadiatop Infant has a limited ability to detect low-grade IgE sensitisation to cow's milk. There were isolated cases of children with weak IgE sensitisation to other allergens but a negative Phadiatop Infant. Furthermore, it is known from several studies that IgE antibodies to food allergens frequently occur during infancy with no evident clinical importance, although some children may develop allergy subsequently (2, 5–7). An ongoing follow-up, when the children in our study are 5 years of age, will show whether these cases of low-grade IgE sensitisation at young ages are only temporary and without clinical importance, or whether they have any impact on the development of allergic phenotypes at older ages.
Eczema and probable bronchial asthma dominated, as expected, as isolated clinical symptoms of allergic diseases among the children studied. Clinical symptoms of allergic disease were more common among children with positive Phadiatop Infant than negative. The difference in the number of clinical symptoms of allergic diseases between children with positive Phadiatop Infant and negative was significant and most pronounced for eczema. Notably, all children with clinical symptoms of allergic diseases and classified as IgE-sensitised had a positive Phadiatop Infant. Conversely, all but one child with clinical symptoms of allergic disease but with negative in vivo and in vitro results for IgE sensitisation showed negative values for Phadiatop Infant. Our results indicate that in the clinical situation, with children that have symptoms of various allergic phenotypes, Phadiatop Infant appears to be a reliable alternative to SPT and the analysis of allergen-specific IgE antibodies to individual allergens in plasma when differentiating allergic children with and without IgE sensitisation. Besides, less serum is required for the analysis, which is not unimportant when testing children. Compared with SPT, Phadiatop Infant has a better reproducibility and is available for all care givers. A recent study points at the advantages of using specific IgE measurements in primary care (24).
This study was performed on children with maternal, biparental or no heredity of allergic diseases and the presence of atopic disease among the parents were carefully characterized. Furthermore, the children were followed prospectively; the presence of IgE sensitisation was evaluated objectively by both SPT and the analysis of IgE antibodies in plasma, and the children were classified without knowing the results for Phadiatop Infant. However, it should be emphasized that the clinical classification of allergic bronchial asthma at this young age is not easy, because wheezing at this age is mostly correlated with bronchial hyper-reactivity in combination with upper respiratory infections and not to IgE sensitisation (8). Another limitation of the study is that the presence of food allergy was based only on case history and SPT and not on food challenge.
In summary, our results indicate that the diagnostic capacity of Phadiatop Infant to detect IgE sensitisation among young children are promising, and equal to the results in previous studies with Phadiatop combined or not with the analysis of allergen-specific IgE antibodies to food allergens (25, 26). Furthermore, among children with clinical symptoms of various allergic phenotypes, e.g. eczema, Phadiatop Infant appears to adequately separate individuals with and without an atopic component of the disease.