Wheat allergy: diagnostic accuracy of skin prick and patch tests and specific IgE

BACKGROUND: Food allergy makes an important contribution to the pathogenesis of atopic eczema in infants. However, clinical data on cereal allergy are scanty. The objective was to study the relevance of patch testing, skin prick tests, and the concentration of wheat-specific IgE antibodies (CAP RAST) in correlation with oral wheat challenge in infants with suspected wheat allergy. In particular, we aimed to determine whether the patch test could increase the diagnostic accuracy in detecting wheat allergy. METHODS: The study material comprised 39 infants under the age of 2 years. Of these patients, 36 were suffering from atopic eczema and three had only gastrointestinal symptoms. The patients were subjected to a double-blind, placebo-controlled or open wheat challenge. Wheat-specific IgE was measured by CAP RAST, and skin prick and patch tests were performed. RESULTS: Of the total 39 wheat challenges, 22 (56%) were positive. Of the positive reactions, five involved immediate-type skin reactions over a period of 2 h from the commencement of the challenge. In 17 patients, delayed-onset reactions of eczematous or gastrointestinal type appeared. Of the infants with challenge-proven wheat allergy, 20% showed elevated IgE concentrations to wheat, 23% had a positive skin prick test, and 86% had a positive patch test for wheat. The specificities of CAP RAST, skin prick tests, and patch tests were 0.93, 1.00, and 0.35, respectively. CONCLUSIONS: Our study demonstrated that patch testing with cereals will significantly increase the probability of early detection of cereal allergy in infants with atopic eczema and is helpful in the planning of successful elimination diets before challenge. The specificity of the patch test was lower than that of other tests. Therefore, confirmation of the diagnosis with the elimination-challenge test is essential in patients with positive patch test results.     

Combined skin prick and patch testing enhances identification of peanut-allergic patients with atopic dermatitis

BACKGROUND: Food atopy patch tests (APTs) are considered a useful tool for the diagnosis of food allergy. Hypersensitivity to peanuts has not been investigated by means of APTs so far. METHODS: APTs and skin prick tests (SPTs) with peanuts were performed in 136 atopic dermatitis (AD) patients. Relevance of positive and negative responses to these tests was assessed by repeated open challenges with peanuts. RESULTS: Nine percent of our AD patients reacted to the challenge. Positive responses to APTs were recorded in 19% of the patients, whereas in 12% positive SPTs were observed. APTs were more frequently positive in subjects with eczematous responses after challenge with respect to those with urticarial reactions. SPT reactivity proved to be higher in patients above 12 years of age, whereas APT positivity was more frequent in children under 6 years. APT sensitivity proved significantly higher than SPT sensitivity, in particular in children under 12 years of age. On the contrary, SPT specificity and positive predictive value were significantly higher with respect to those of APT in the age group of subjects under 6 years of age. CONCLUSIONS: Our data suggest that APTs with peanuts may represent a useful integration to standard testing modalities employed for the diagnosis of peanut allergy in AD patients.     

Concurrent cereal allergy in children with cow''s milk allergy manifested with atopic dermatitis

BACKGROUND: There is increasing consensus about the significance of food allergens in the pathogenesis of atopic dermatitis (AD) in infancy and childhood, with cow's milk and egg accounting for most of the reactions. Previous studies have indicated that multiple food sensitization, such as cereals, is very common in patients with cow's milk allergy (CMA). Evidence is lacking, however, as to its clinical relevance. OBJECTIVE: The purpose of this study was to determine the concurrent occurrence of cereal allergy among children with challenge-proven CMA who have residual symptoms, such as AD and/or gastrointestinal symptoms, during cow's milk elimination diet. Further, we sought to evaluate the utility of patch testing in prescreening foods other than cow's milk behind allergic symptoms in children. METHODS: The study population comprised 90 children, aged from 2.5 to 36 months (mean 1.1 years), with challenge-proven CMA. As a result of residual symptoms during meticulous cow's milk elimination diet (AD: n=80, and gastrointestinal: n=10), the children were put on a cereal elimination diet (oats, wheat, rye, and barley) and skin prick tests (SPT) and patch testing with cereals were performed. Open cereal challenge was performed to confirm cereal allergy. RESULTS: Cereal challenge was positive in 66 (73%) of the children with CMA. Of them, 17% reacted with immediate reactions and delayed-onset reactions were seen in 83% of the children. SPT was positive in 23%, patch test in 67%, and either SPT or patch test was positive in 73% of the children with cereal allergy. SPT gave the best positive predictive value, whereas SPT together with patch test gave the best negative predictive value. CONCLUSIONS: Residual symptoms, such as eczema or gastrointestinal symptoms in CMA children may be a sign of undetected allergy to other food antigens. SPT with cereals aids in diagnosing cereal allergy in small children, especially when used together with patch testing.     

Atopic dermatitis and skin allergies – update and outlook

During the last few years, an impressive amount of experimental studies and clinical trials have dealt with a variety of distinct topics in allergic skin diseases – especially atopic dermatitis. In this update, we discuss selected recent data that provide relevant insights into clinical and pathophysiological aspects of allergic skin diseases or discuss promising targets and strategies for the future treatment of skin allergy. This includes aspects of barrier malfunction and inflammation as well as the interaction of the cutaneous immune system with the skin microbiome and diagnostic procedures for working up atopic dermatitis patients. Additionally, contact dermatitis, urticaria, and drug reactions are addressed in this review. This update summarizes novel evidence, highlighting current areas of uncertainties and debates that will stimulate scientific discussions and research activities in the field of atopic dermatitis and skin allergies in the future.     

Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects

This review highlights some of the research advances in anaphylaxis and hypersensitivity reactions to foods, drugs, and insects and in allergic skin disease that were reported primarily in the Journal in 2006. Advances in diagnosis include identification of food proteins to which IgE binding is associated with severe reactions; elucidation of diagnostic relationships of skin prick test wheal size with outcomes of egg, tree nut, and sesame allergy; evaluation of the diagnostic utility of atopy patch testing for food; and the observation that yellow jacket sting outcomes are influenced by species. Mechanistic observations include the following: heating of birch pollen-related foods disrupts IgE binding but not T-cell epitopes; a simple imbalance of T(H)1/T(H)2 response does not explain variations in clinical expression of peanut allergy; and elucidation of the role of dendritic cells in drug hypersensitivity. With regard to treatment, a rapidly disintegrating epinephrine tablet showed promise for sublingual treatment of anaphylaxis, RNA interference techniques showed promise in creating lower-allergenic foods, and anti-IL-5 showed promise for treatment of eosinophilic esophagitis. Progress in our understanding of the immunology and the etiology of skin barrier dysfunction in atopic dermatitis has also been made. These observations will likely contribute toward optimizing management of these common allergic disorders.     

Immediate hypersensitivity to Malassezia furfur and Candida albicans mannans in vivo and in vitro

BACKGROUND: Elevated and correlative Malassezia furfur (M. furfur) and Candida albicans (C. albicans) mannan-specific IgE have been demonstrated in atopic eczema dermatitis syndrome (AEDS) of the head, neck and shoulder (HNS) region of the skin. The significance of these antibodies in vivo has not been demonstrated. METHODS: Sixty-five AEDS patients with HNS distribution were included. Serum total IgE (S-IgE) and yeast antigen-specific (Cetavlon-purified mannan and whole extract antigens of M. furfur and C. albicans) IgE were measured and skin prick tests (SPT) were performed with the yeast antigens. RESULTS: Mannan-specific IgE and SPT were positive in 51 and 48% of patients with M. furfur and in 42 and 22% with C. albicans, respectively. Whole extract-specific IgE and SPT were positive in 85 and 95% of patients with M. furfur and in 91 and 57% with C. albicans, respectively. The highest correlation between specific IgE and SPT was seen with M. furfur mannan (r = 0.60; P < 0.0001). Both M. furfur mannan-specific IgE (r = 0.76; P < 0.0001) and SPT (r = 0.44; P = 0.0005) correlated with S-IgE. CONCLUSIONS: Mannan-induced immediate hypersensitivity in vivo was demonstrated in SPT. The significant correlation between M. furfur mannan-specific IgE and SPT suggests that mannan is an important allergen in yeast hypersensitive AEDS in vivo.     

Eczematous reactions to food in atopic eczema: position paper of the EAACI and GA2LEN

Food allergy and atopic eczema (AE) may occur in the same patient. Besides typical immediate types of allergic reactions (i.e. noneczematous reactions) which are observed in patients suffering from AE, it is clear that foods, such as cow's milk and hen's eggs, can directly provoke flares of AE, particularly in sensitized infants. In general, inhaled allergens and pollen-related foods are of greater importance in older children, adolescents and adults. Clinical studies have revealed that more than 50% of affected children with AE that can be exacerbated by certain foods will react with a worsening of skin eczema either alone or in addition to immediate symptoms. Adolescents and adults may also react to foods, but reactions to 'classical' food allergens, such as hen's eggs and cow's milk, are not as common as in childhood. Some patients with AE do react to pollen-associated foods. Food-induced eczema should not be neglected by the allergologist: On the one hand, food can be a relevant trigger factor of persistent moderate-to-severe AE; on the other hand, unnecessary diets which are not based on a proper diagnosis may lead to malnutrition and additional psychological stress on patients suffering from AE. Eczematous reactions to food can only be diagnosed by a thorough diagnostic procedure, taking into account the patient's history, the degree of sensitization and the clinical relevance of the sensitization. The latter has often to be proven by oral food challenges. Upon oral food challenge it is most important to evaluate the status of the skin with an established score (e.g. SCORAD, EASI) after 24 h and later because otherwise worsening of eczema will be missed.     

The temporal sequence of allergic sensitization and onset of infantile eczema

BACKGROUND: Eczema is commonly associated with sensitization in infants, but the causative role of sensitization in the development of eczema has been questioned. OBJECTIVE: To determine if allergic sensitization increases the risk of developing eczema, or alternatively, if eczema increases the risk of developing allergic sensitization. METHODS: We used data from the Melbourne Atopy Cohort Study, a prospective birth cohort of 552 infants with a family history of atopic disease. The main outcomes were risk of developing eczema from 6 months to 7 years of age in asymptomatic infants; and risk of developing sensitization, as measured by skin prick tests to milk, egg white, peanut, house dust mite, rye grass pollen and cat extracts, in previously unsensitized infants. RESULTS: Sensitization to food extracts at 6 months was associated with an increased risk of developing eczema [hazard ratio (HR) 1.63, 95% confidence interval 1.13-2.35] up to 7 years of age, after excluding infants with eczema in the first 6 months. However, eczema in the first 6 months was also associated with increased risk of new sensitization at both 1 year (HR 2.34, 1.38-3.98) and 2 years (HR 3.47, 1.65-7.32). CONCLUSION: In some infants, sensitization precedes and predicts the development of eczema, while in others eczema precedes and predicts the development of sensitization. This indicates that there are multiple pathways to atopic eczema.     

Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2011

This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin diseases that were reported in the Journal in 2011. Food allergy appears to be increasing in prevalence and carries a strong economic burden. Risk factors can include dietary ones, such as deficiency of vitamin D and timing of complementary foods, and genetic factors, such as filaggrin loss-of-function mutations. Novel mechanisms underlying food allergy include the role of invariant natural killer T cells and influences of dietary components, such as isoflavones. Among numerous preclinical and clinical treatment studies, promising observations include the efficacy of sublingual and oral immunotherapy, a Chinese herbal remedy showing promising in vitro results, the potential immunotherapeutic effects of having children ingest foods with baked-in milk if they tolerate it, and the use of anti-IgE with or without concomitant immunotherapy. Studies of allergic skin diseases, anaphylaxis, and hypersensitivity to drugs and insect venom are elucidating cellular mechanisms, improved diagnostics, and potential targets for future treatment. The role of skin barrier abnormalities, as well as the modulatory effects of the innate and adaptive immune responses, are major areas of investigation.     

EAACI/GA2LEN position paper: present status of the atopy patch test

A number of scientific reports have been published on patch tests with protein allergens performed on patients with atopic eczema (AE). Evaluation of eczematous skin lesions with an atopy patch test (APT) can be used as a diagnostic tool in characterizing patients with aeroallergen- and food-triggered AE. Indications for testing with APT, choice of allergens (aeroallergens and foods), test materials and technique, including present knowledge on sensitivity and specificity, are reviewed on the basis of available literature. This position paper also points out the need for future research on the clinical use of the APT.     

Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2007

This review highlights some of the research advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects that were reported primarily in the Journal in 2007. Advances in diagnosis include possible biomarkers for anaphylaxis, improved understanding of the relevance of food-specific serum IgE tests, identification of possibly discriminatory T-cell responses for drug allergy, and an elucidation of irritant responses for vaccine allergy diagnostic skin tests. Mechanistic studies are discerning T-cell and cytokine responses central to eosinophilic gastroenteropathies and food allergy, including the identification of multiple potential therapeutic targets. Regarding treatment, clinical studies of oral immunotherapy and allergen vaccination strategies show promise, whereas several clinical studies raise questions about whether oral allergen avoidance reduces atopic risks and whether probiotics can prevent or treat atopic disease. The importance of skin barrier dysfunction has been highlighted in the pathogenesis of atopic dermatitis (AD), particularly as it relates to allergen sensitization and eczema severity. Research has also continued to identify immunologic defects that contribute to the propensity of patients with AD to have viral and bacterial infections. New therapeutic approaches to AD, urticaria, and angioedema have been reported, including use of sublingual immunotherapy, anti-IgE, and a kallikrein inhibitor.     

Atopic dermatitis: a disease of altered skin barrier and immune dysregulation

Atopic dermatitis (AD) is an important chronic or relapsing inflammatory skin disease that often precedes asthma and allergic disorders. New insights into the genetics and pathophysiology of AD point to an important role of structural abnormalities in the epidermis as well as immune dysregulation not only for this skin disease but also for the development of asthma and allergies. Patients with AD have a unique predisposition to colonization or infection by microbial organisms, most notably Staphylococcus aureus and herpes simplex virus. Measures directed at healing and protecting the skin barrier and addressing the immune dysregulation are essential in the treatment of patients with AD, and early intervention may improve outcomes for both the skin disease as well as other target organs.     

Breast-feeding and atopic eczema dermatitis syndrome: protective or harmful?

Numerous studies have addressed the potential of breast-feeding to protect for the development of allergic diseases, and in particular of atopic eczema dermatitis syndrome (AEDS). Although the majority of studies, as well as several meta-analyses, are strongly in favour of breast-feeding, there are some conflicting results and open issues. Furthermore, breast-feeding might be detrimental in a subgroup of young infants with severe early manifestations of AEDS and immunoglobulin E sensitizations to common foods. The aim of this review is not to analyse systematically the current literature, but to suggest a scientifically and clinically based analysis of the benefits of breast-feeding in atopic infants.