Gastroesophageal reflux disease, colic and constipation in infants with food allergy

PURPOSE OF REVIEW: This review assesses the role of food allergy in the pathophysiology of gastroesophageal reflux disease, colic and constipation in infancy. RECENT FINDINGS: Frequent regurgitation, persistent crying and constipation are common clinical problems in infancy. A subgroup of infants with these conditions may respond to hypoallergenic diets, but only few randomized clinical trials have been conducted. Skin prick testing and food-specific antibody levels are usually not elevated in these infants, whereas atopy patch testing may diagnostic. The mechanisms by which cow's milk and other food allergens induce gastrointestinal motility disorders are not understood. Apart from cell-mediated reactions, non-immunological effects of food constituents on gastrointestinal motility and gut microbiota may be involved in the pathogenesis. In the absence of reliable diagnostic tests, dietary elimination and re-challenge are usually required to confirm food allergy. A trial of amino acid-based formula or an oligoantigenic maternal elimination diet may be indicated in infants who have failed conventional medical treatment. SUMMARY: Food allergy may contribute to gastroesophageal reflux disease, colic or constipation in infancy. Infants with these conditions often respond to hypoallergenic formula or a maternal elimination diet. Further research is needed to define the mechanisms and clinical markers of gastrointestinal food allergy in infancy.     

Cow's milk allergy in infancy

Cow's milk allergy affects approximately 2% of infants under 2 years of age. This review summarizes the recent advances in understanding its pathophysiology and immunological mechanisms. Apart from IgE-mediated atopic manifestations, T cell-mediated reactions have been demonstrated in infants with cow's milk allergy. The clinical spectrum ranges from immediate-type reactions, presenting with urticaria and angioedema to intermediate and late-onset reactions, including atopic dermatitis, infantile colic, gastro-oesophageal reflux, oesophagitis, infantile proctocolitis, food-associated enterocolitis and constipation. The exact mechanisms of these disorders are still poorly understood. Double-blind, placebo controlled food challenge, the definitive diagnostic test for cow's milk allergy, is increasingly being replaced by the measurement of food-specific antibodies, in combination with skin-prick or atopy patch testing. The treatment of cow's milk allergy relies on allergen avoidance and hypoallergenic formulae, or maternal elimination diets in breast-fed infants.     

Clinical Spectrum of Food Allergies: a Comprehensive Review

Food allergy is defined as an adverse immune response towards food proteins or as a form of a food intolerance associated with a hypersensitive immune response. It should also be reproducible by a double-blind placebo-controlled food challenge. Many reported that food reactions are not allergic but are intolerances. Food allergy often presents to clinicians as a symptom complex. This review focuses on the clinical spectrum and manifestations of various forms of food allergies. According to clinical presentations and allergy testing, there are three types of food allergy: IgE mediated, mixed (IgE/Non-IgE), and non-IgE mediated (cellular, delayed type hypersensitivity). Recent advances in food allergy in early childhood have highlighted increasing recognition of a spectrum of delayed-onset non-IgE-mediated manifestation of food allergy. Common presentations of food allergy in infancy including atopic eczema, infantile colic, and gastroesophageal reflux. These clinical observations are frequently associated with food hypersensitivity and respond to dietary elimination. Non-IgE-mediated food allergy includes a wide range of diseases, from atopic dermatitis to food protein-induced enterocolitis and from eosinophilic esophagitis to celiac disease. The most common food allergies in children include milk, egg, soy, wheat, peanut, treenut, fish, and shellfish. Milk and egg allergies are usually outgrown, but peanut and treenut allergy tends to persist. The prevalence of food allergy in infancy is increasing and may affect up to 15–20 % of infants. The alarming rate of increase calls for a public health approach in the prevention and treatment of food allergy in children.     

Eosinophilic esophagitis is characterized by a non‐IgE‐mediated food hypersensitivity

Eosinophilic esophagitis (EoE) is a chronic disease characterized clinically by symptoms of esophageal dysfunction and histologically by eosinophil‐predominant inflammation. EoE is frequently associated with concomitant atopic diseases and immunoglobulin E (IgE) sensitization to food allergens in children as well as to aeroallergens and cross‐reactive plant allergen components in adults. Patients with EoE respond well to elemental and empirical food elimination diets. Recent research has, however, indicated that the pathogenesis of EoE is distinct from IgE‐mediated food allergy. In this review, we discuss the individual roles of epithelial barrier defects, dysregulated innate and adaptive immune responses, and of microbiota in the pathogenesis of EoE. Although food has been recognized as a trigger factor of EoE, the mechanism by which it initiates or facilitates eosinophilic inflammation appears to be largely independent of IgE and needs to be further investigated. Understanding the pathogenic role of food in EoE is a prerequisite for the development of specific diagnostic tools and targeted therapeutic procedures.     

Introducing chemists to food allergy

Adverse reactions to food may be toxic or non toxic, depending on the susceptibility to a certain food; non toxic reactions that involve immune mechanisms are termed allergy if they are IgE-mediated. If no immunological mechanism is responsible, it is termed intolerance . The following disorders are considered a consequence of food allergy: gastrointestinal reactions (oral allergy syndrome, vomiting, diarrhea, protein-induced enterocolitic syndrome, eosinophilic gastroenteritis); respiratory reactions (rhinitis, asthma, laryngeal edema); cutaneous reactions (urticaria-angioedema, atopic dermatitis); anaphylaxis. There is much recent evidence to consider celiac disease an immunological disorder. Food allergy diagnosis is based on history, SPT, specific IgE, food challenges. DBPCFC is fundamental for diagnosing true food allergy; patients who have had anaphylaxis to food must not undergo DBPCFC. Rapidly progressive respiratory reactions and anaphylactic shock are life-threatening reactions that can be caused by food allergy. The doses of food inducing anaphylaxis can be very low, therefore commercial cross-contamination with an unsuspected food during food processing can be risky for the food allergic patient. The prevention of severe anaphylactic food reactions may lie in interdisciplinary collaboration among allergologists, chemists, food technologists, and experts in food industry research.     

The Changing Geoepidemiology of Food Allergies

The science of food allergy has been rapidly evolving before our eyes in the past half century. Like other allergic disorders, the prevalence of food allergies has dramatically increased, and coupled with the increased public awareness of anaphylaxis due to food allergy, this has driven an explosion in basic and clinical research in this extremely broad subject. Treatment of food allergies has evolved and practices such as food challenges have become an integral part of an allergy practice. The impact of the increase of food allergy has driven package labeling laws, legislation on emergency treatment availability in schools and other public places, and school policy. But to this day, our knowledge of the pathogenesis of food allergy is still incomplete. There are the most obvious IgE-mediated immediate hypersensitivity reactions, but then multiple previously unidentified conditions such as eosinophilic esophagitis, food protein-induced enterocolitis syndrome, milk protein allergy, food-induced atopic dermatitis, oral allergy syndrome, and others have complicated the diagnosis and management of many of our patients who are unable to tolerate certain foods. Many of these conditions are not IgE-mediated, but may be T cell-driven diseases. The role of T regulatory cells and immune tolerance and the newly discovered immunological role of vitamin D have shed light on the variable clinical presentation of food allergy and the development of new methods of immunotherapy in an example of bench-to-bedside research. Component-resolved diagnostic techniques have already begun to allow us to more precisely define the epitopes that are targeted in food allergic patients. The development of biological modulators, research on genomics and proteomics, and epigenetic techniques all offer promising avenues for new modes of therapy of food allergy in the twenty-first century.     

Improving in-vitro tests for the diagnosis of food hypersensitivity

Food hypersensitivity reactions affect up to 8% of children under 3 years of age and approximately 2.5% of the general United States population. Food allergic disorders may be subdivided into either IgE-mediated or cell-mediated reactions. The diagnostic 'gold standard' of 'symptomatic' food allergies remains the blinded oral food challenge because of the poor specificity of patient histories, skin testing and standard radioallergosorbent tests, and the outcomes of elimination diets. Little progress has been made in the development of in-vitro tests for the diagnosis of cell-mediated food hypersensitivities. However, new developments in in-vitro technologies have improved the capabilities of these tests to diagnose IgE-mediated reactivity and perhaps predict the development of future 'tolerance', i.e. 'outgrowing' the allergy.     

Food allergy – accurately identifying clinical reactivity

Up to 25% of adults believe that they or their children are afflicted with a food allergy. However, the actual prevalence of food allergy is much lower: approximately 6–8% of children suffer from food allergy during their first 3 years of life, and many children then develop clinical tolerance. Food allergy encompasses a whole spectrum of disorders, with symptoms that may be cutaneous, gastrointestinal or respiratory in nature. Food disorders also differ according to the extent that they are immunoglobulin E (IgE)-mediated. Skin-prick testing is often used to identify food sensitization, although double-blind, placebo-controlled food challenge (DBPCFC) tests remain the gold standard for diagnosis. Recent evidence suggests that quantitative IgE measurements can predict the outcome of DBPCFC tests and can replace about half of all oral food challenges. When an extensive medical history is obtained in combination with IgE quantification, even fewer patients may require formal food challenges. It has also become possible to map the IgE-binding regions of many major food allergens. This may help to identify children with persistent food allergy, as opposed to those who may develop clinical tolerance. In future, microarray technology may enable physicians to screen patients for a large number of food proteins and epitopes, using just a few drops of blood.     

Human milk-specific mucosal lymphocytes of the gastrointestinal tract display a TH2 cytokine profile

BACKGROUND: A number of gastrointestinal disorders, including allergic eosinophilic gastroenteritis and food protein-induced enteropathy, have been associated with milk hypersensitivity. The immunologic reactions appear to involve T cells that are activated by specific food proteins. OBJECTIVE: The present study was performed to examine the cytokine profiles of milk-specific lymphocytes from the duodenal lamina propria from children with milk-induced gastrointestinal diseases. METHODS: Duodenal biopsy specimens obtained from 10 patients with allergic eosinophilic gastroenteritis, food protein-induced enteropathy, or both and 12 control subjects were mechanically minced and cultured with either mitogens (i.e., polyclonal T-cell expansion) or milk proteins (i.e., milkspecific T-cell expansion). By using flow cytometry, expanded T cells were phenotyped with anti-CD4, anti-CD8, anti-IL-4, anti-IL-5, and anti-IFN-gamma mAbs. The milk specificity of the lines was evaluated by means of the lymphocyte proliferation assay. In addition, the release of T(H)1, T(H)2, and T(H)3 cytokines was determined after restimulation. RESULTS: In patients and control subjects polyclonal expansion of mucosal lymphocytes resulted in predominantly T(H)1 cells. Milk-specific mucosal T-cell lines could be established in 60% of the patients but in none of the control subjects. In contrast to the polyclonal expansion of T cells, the milk-specific expansion of mucosal T cells showed a clear T(H)2 cytokine profile. On restimulation with milk protein, these cells showed a high proliferative response. They released T(H)2 cytokines, predominately IL-13, but failed to release T(H)3 cytokines important in the development of oral tolerance. CONCLUSION: The release of T(H)2 cytokines after stimulation of milk-specific mucosal T cells may play a pathogenic role in the inflammatory changes seen in milk-induced gastrointestinal disorders.     

Diagnostic oral food challenges: procedures and biomarkers

Oral food challenge (OFC) is the gold standard for the diagnosis of food allergy. They are conducted to confirm whether an allergy to food exists (initial challenge) or to monitor for resolution of a food allergy. The history of an immediate allergic reaction, when supported by positive tests for specific IgE antibodies to the suspect food, is often sufficient to establish a diagnosis without OFC. Additionally, higher concentrations of food-specific IgE or larger allergy prick skin test wheal sizes correlate with an increased likelihood of a reaction upon ingestion. Although these food-specific IgE tests are helpful biomarkers of allergy, their limited sensitivity and specificity often necessitates the use of OFC to establish reactivity. Furthermore, the pathogenesis of non-IgE-mediated food allergy, such as food protein-induced enterocolitis (FPIES) or proctocolitis and food allergy due to mixed IgE and non-IgE mediated processes, such as atopic dermatitis or eosinophilic gastroenteropathies may not be assessable with specific IgE tests, also warranting OFCs. This review provides an overview on the technique and interpretation of OFCs, use of food-specific testing to predict whether OFC is warranted and to predict OFC outcomes. Additionally, biomarkers that correlate with OFC outcomes will be discussed, as well as future diagnostic tests promising better predictive value.     

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.     

Food allergy diagnostics: scientific and unproven procedures

PURPOSE OF REVIEW: The accurate diagnosis of food allergy is crucial not only for the right treatment but also for the avoidance of unnecessary diets. The diagnostic work-up of suspected food allergy includes the measurement of food-specific IgE antibodies using serologic assays, the skin prick test, elimination diets and oral provocation tests. In addition, some approaches are either under further rigorous investigation (the atopy patch test) or are already in widespread use, particularly by practitioners of alternative or complementary medicine, but are considered unproven. These diagnostic methods include specific IgG to foods, provocation/neutralization testing, kinesiology, cytotoxic tests and electrodermal testing. This review covers some of the most common scientifically validated and unproven approaches used in the diagnosis of food allergy. RECENT FINDINGS: For specific serum IgE and the SPT, decision points have been established for some foods, allowing prediction of clinical relevance. The APT may be helpful, especially when considered in combination with defined levels of specific IgE. In regard to other approaches, most scientific studies do refute the usefulness of these approaches. SUMMARY: In most patients, controlled oral food challenges remain the gold standard in the diagnostic work-up of suspected food allergy. The skin prick test and measurement of specific IgE antibodies to food extracts, individual allergens or allergenic peptides are helpful in the diagnostic approach. Food-specific IgG continues to be an unproven or experimental test. The other alternative and complementary techniques have no proven benefit and may endanger patients via misdiagnosis.     

Unproven diagnostic procedures in IgE-mediated allergic diseases

A considerable body of literature on therapeutic aspects of complementary and alternative medicine has been published in recent years, but little is known on diagnostic procedures. This short review lists complementary and alternative diagnostic procedures for the diagnosis of allergic diseases and presents an assessment of their usefulness for the daily practice. The review of the literature revealed that neither the determination of specific immunoglobulin G-antibodies in serum, the hair-analysis, the cytotoxic test, kinesiology, iridology, or electrodermal testing represent useful tests for the daily practice. To date, no complementary or alternative diagnostic procedure can be recommended as a meaningful element in the diagnostic work-up of allergic diseases. This is especially true for food allergy: properly performed oral food challenges still represent the gold standard for implementing specific diets in food allergic individuals. Ineffective diagnostic approaches may be costly for the consumer and delay appropriate therapy.     

Oesophagitis in children: reflux or allergy?

The prevalence of eosinophilic oesophagitis appears to be increasing in many countries, sometimes rapidly, although this may be partly due to increased disease recognition. Histological methods of assessment and diagnostic criteria vary considerably between major clinical centres. Oesophagitis with over 20 intraepithelial eosinophils per high power field is more likely to be due to allergy than gastro-oesophageal reflux induced acid-peptic mucosal injury. Typical eosinophilic oesophagitis shows involvement of the entire oesophagus, with basal cell proliferation occupying more than 50% of the thickness of the surface epithelium, and high numbers of intraepithelial eosinophils, sometimes concentrated on the surface or as contiguous clusters. Ulceration and prominent neutrophils are atypical and should suggest an alternative or co-existent disease. On endoscopy, the oesophagus may display the typical 'corrugated' mucosal appearance. Clinically, dysphagia or food impaction are the most characteristic symptoms. There is a strong association with other atopic diseases, especially asthma and eczema. To date no evidence has emerged of an increased malignancy risk. Patients with eosinophilic oesophagitis typically fail to respond to acid suppressive medications but respond well to either elemental/elimination diets or aerosolised swallowed corticosteroids. Long-term uncontrolled oesophageal eosinophilic inflammation may lead to progressive subepithelial fibrosis, potentially resulting in strictures or oesophageal narrowing.     

Food allergen avoidance in primary prevention of food allergy

Approximately 5–10% of children suffer from allergy to one or more foods. Primary prevention through a hypoallergenic diet may reduce the prevalence of food allergy and associated co-morbidity, such as eczema and urticaria. Breastfeeding has many advantages and should be recommended for all children. Those with a history of atopy in the immediate family are at a higher risk and maternal diet during lactation, avoiding highly allergenic foods, may enhance the benefit. Cow's milk should be strictly avoided, and supplements, if required, should be with a hypoallergenic formula. Delayed introduction of egg, nuts, wheat and fish has also been suggested. Dietary restriction may have nutritional consequences for the mother and child and supervision by a dietician is essential. Maternal diet during pregnancy is not advisable as the benefit is minimal and there may be adverse effects on the foetal nutrition. In high risk infants, a combined approach, where breastfeeding with maternal avoidance of highly allergenic foods, supplemented by extensively hydrolysed formula during the first 6 months of life, in addition to the delayed introduction of solid foods, has been shown to reduce the development of food allergy in infants.     

IgE and non-IgE-mediated food allergy: treatment in 2007

PURPOSE OF REVIEW: Our understanding of the mechanism of food allergy has substantially increased over the past decade. Food allergies can be classified into those that are IgE mediated and those that are non-IgE mediated. RECENT FINDINGS: Various advances have been made in treating IgE-mediated food allergies. A phase II clinical trial of a second anti-IgE antibody, omalizumab, was recently initiated in subjects with peanut allergy, but was stopped as a result of safety concerns after severe reactions occurred during initial oral challenges. Oral immunotherapy is showing promise in various studies on patients with IgE-mediated food allergies. Gastrointestinal food allergic disorders involving non-IgE-mediated food allergies have recently received attention, particularly eosinophilic esophagitis. Although amino acid-based formula therapy remains the most successful in controlling inflammation and symptoms in these disorders, other therapeutic options including various dietary elimination protocols and swallowed fluticasone are showing success. Anti-IL-5 therapy may prove to be a promising future therapeutic option for refractory patients. SUMMARY: Although there are no specific therapeutic recommendations for many IgE-mediated and non-IgE-mediated food allergic disorders besides allergen avoidance, various novel approaches are currently being investigated and may influence treatment approaches in the future.     

Food hypersensitivity in children

Food hypersensitivity affects children and adults with an increasing prevalence, and is therefore an important public health problem in the majority of developed countries. Moreover, self-reported reactions to food are of several times higher prevalence, compared to hypersensitivity diagnosed following well established evidence-based diagnostic guidelines. In children, allergic food reactions are more common compared to non-allergic food hypersensitivity reactions, and 90% of them are caused with only 8 food allergens: cow's milk, soya, egg, fish, shellfish, peanut, tree-nuts and gluten. Diagnosis should be based on challenge tests with the potentially offending food allergens. Concerning other, more conservative diagnostic procedures, negative serology and negative skin-prick tests can exclude IgE-mediated food allergy, but positive tests, due to high rate of false positive reactions are not sufficient for diagnosis. Strict dietary avoidance of incriminated allergens is the only well established management strategy. However, this should be applied only if food allergy is well documented - following the exposition tests. Introducing elimination diet in a paediatric population, particularly with the elimination of multiple foods, could cause inappropriate growth and disturb organ maturation. Concerning allergy prevention, avoidance of allergens is not efficacious either during pregnancy and lactation or weaning period, and is therefore, not recommended neither as a population preventive measure, nor in children at risk.     

Prevalence of food allergies in young adults and their relationship to asthma, nasal allergies, and eczema.

BACKGROUND: The true prevalence of food allergy in adults is generally thought to be uncommon. It is unknown whether there are any relationships between food allergy and atopic diseases. OBJECTIVE: To determine the prevalence of probable immunoglobulin (Ig)E-mediated food allergy to peanut, shrimp, cow's milk, wheat, and egg as defined by a positive skin prick test result and relevant clinical history to the same food, and to explore the relationship with atopic diseases. METHODS: Cross-sectional epidemiologic study. One thousand one hundred forty-one randomly selected young adults (aged 20 to 45 years) underwent skin prick testing to five common food allergens (cow's milk, peanut, egg white, shrimp, and wheat), completed a detailed questionnaire, including validated items on respiratory symptoms, history of asthma and other allergic conditions, as well as undergoing lung function testing. RESULTS: Just over one percent (1.3%, n = 15) had probable IgE-mediated food allergy. The prevalence of probable IgE food allergy was: <0.27% for wheat, 0.09% (95% confidence interval = 0.0 to 0.49%) each for cow's milk and egg, 0.53% (0.21 to 1.09%) for shrimp, and 0.61% (0.25 to 1.26%) for peanut. Those with probable IgE peanut and shrimp allergy were significantly more likely to have current asthma and doctor-diagnosed asthma. Wheeze and history of eczema were also associated with peanut allergy, whereas nasal allergies were associated with shrimp allergy. CONCLUSIONS: The prevalence of probable IgE-mediated food reactions is rare in young adults. Some positive associations between probable IgE-mediated food allergy and allergic diseases were found, but larger study numbers are required to confirm these results.     

Primary prevention of food allergy in infants who are at risk

PURPOSE OF REVIEW: Allergic diseases represent a major burden of health problems in industrialized countries. Though several studies have focused on possible preventive measure and strategies much controversy still exists on this topic. The aim of this review is to discuss the recent literature on primary prevention of food allergy. RECENT FINDINGS: In prospective observational controlled studies of high quality of birth cohorts, exclusive breastfeeding for at least 4 months combined with introduction of solid foods after 4 months of age is associated with a reduced risk of food allergy and atopic dermatitis, particularly in high-risk infants. When breastfeeding for 4-6 months is not possible or insufficient, randomized controlled trials have shown a significant reduction in food allergy and atopic dermatitis in high-risk infants fed a documented hypoallergenic hydrolysed formula. SUMMARY: Breastfeeding should be encouraged for 4-6 months. In high-risk infants a documented hypoallergenic hydrolysed formula is recommended if exclusively breastfeeding is not possible for the first 4 months. As regards primary prevention of food allergy there is no evidence for preventive dietary intervention during neither pregnancy nor lactation. Likewise, preventive dietary restrictions after the age of 4-6 months are not scientifically documented.     

The atopy patch test (APT)-- a useful tool for the diagnosis of food allergy in children with atopic dermatitis

BACKGROUND: While immediate-type clinical reactions to food can quite easily be identified by history or measurement of specific IgE in combination with positive oral food challenges, the evaluation of food allergy in the absence of immediate clinical reactions still presents diagnostic difficulties--particularly in children with atopic dermatitis. The objective of this study was to evaluate the diagnostic value of the atopy patch test (APT) with regard to late-phase reactions observed in double-blind, placebo-controlled food challenges with cow's milk, hen's egg, wheat, and soybean. METHODS: We investigated 75 children (median age 2.1 years) with suspected food allergy by double-blind, placebo-controlled food challenges, specific IgE in serum, skin prick test, and APT. Of the subjects, 69/75 suffered from atopic dermatitis. RESULTS: Of 209 oral challenges, 133 were performed with allergen and 76 with placebo. We assessed 77/133 allergen and 2/76 placebo challenges as positive. In 66 of 77 (86%) positive oral challenges, specific IgE in serum to the corresponding allergen was positive; in 64/77 (83%) the skin prick test, and in 42/77 (55%) the APT was positive. While immediate-type reactions were associated with positive skin prick test and proof of specific IgE in serum, late-phase clinical reactions were associated with a positive APT (sensitivity 76%, specificity 95%). CONCLUSIONS: The APT seems to be a valuable additional tool in the diagnostic work-up of food allergy in children with atopic dermatitis - especially with regard to late-phase clinical reactions. The APT may help to prevent unnecessary restrictive diets which may be the consequence of misjudging late reactions by clinical assessment alone.