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.     

Comparison of high resolution chromosome banding and fluorescence in situ hybridization (FISH) for the laboratory evaluation of Prader-Willi syndrome and angelman syndrome

The development of probes containing segments of DNA from chromosome region 15q11-q13 provides the opportunity to confirm the diagnosis of Prader-Willi syndrome (PWS) and Angelman syndrome (AS) by fluorescence in situ hybridization (FISH). We have evaluated FISH studies and high resolution chromosome banding studies in 14 patients referred to confirm or rule out PWS and five patients referred to confirm or rule out AS. In four patients (three from the PWS category and 1 from the AS group) chromosome analysis suggested that a deletion was present but FISH failed to confirm the finding. In one AS group patient, FISH identified a deletion not detectable by high resolution banding. Review of the clinical findings in the discrepant cases suggested that the FISH results were correct and high resolution findings were erroneous. Studies with a chromosome 15 alpha satellite probe (D15Z) on both normal and abnormal individuals suggested that incorrect interpretation of chromosome banding may occasionally be attributable to alpha satellite polymorphism but other variation of 15q11-q13 chromosome bands also contributes to misinterpretation. We conclude that patients who have been reported to have a cytogenetic deletion of 15q11-q13 and who have clinical findings inconsistent with PWS and AS should be reevaluated by molecular genetic techniques. © 1994 Wiley-Liss, Inc.     

Bronchial challenges with aerosolized food in asthmatic,food-allergic children

BACKGROUND: Allergic asthma is usually considered to be provoked by aeroallergens. However, we have recently recognized a group of children with food allergies who also develop asthma when exposed to the aerosolized form of the food. METHODS: Between 1997 and 1999 we prospectively identified children with an immunoglobulin (Ig)E-mediated food allergy who develop asthma on inhalational exposure to the relevant food allergen while it is being cooked. Subjects were exposed for 20 min to the aerosolized form of the allergen and the symptoms and the lung function were monitored. Aerosolization was achieved by cooking the food in a small room. Where possible challenges were double-blinded. RESULTS: We identified 12 children with an IgE-mediated food allergy who developed asthma on inhalational exposure to food. The implicated foods were fish, chickpea, milk, egg or buckwheat. Nine out of the 12 children consented to undergo a bronchial food challenge. Five challenges were positive with objective clinical features of asthma. Additionally, two children developed late-phase symptoms with a decrease in lung function. Positive reactions were seen with fish, chickpea and buckwheat. There were no reactions to the seven placebo challenges. CONCLUSIONS: We have presented a prospective series of children with food allergy who developed symptoms of asthma with exposure to aerosolized food allergens. Our data demonstrates that, as in the case of other aeroallergens, inhaled food allergens can produce both early- and late-phase asthmatic responses. This highlights the importance of considering foods as aeroallergens in children with coexistent food allergy and allergic asthma. For these children, dietary avoidance alone may not be sufficient and further environmental measures may be required to limit exposure to aerosolized food.     

Severe food allergies by skin contact.

BACKGROUND: Ingestion is the principal route for food allergens, yet some highly sensitive patients may develop severe symptoms upon skin contact. CASE REPORT: We describe five cases of severe food allergic reactions through skin contact, including inhalation in one. METHODS: The cases were referred to a university allergy clinic, and evaluation comprised detailed medical history, physical examination, skin testing, serum total and specific IgE, and selected challenges. RESULTS: These cases were found to have a strong family history of allergy, early age of onset, very high total serum IgE level, and strong reactivity to foods by skin prick testing or RAST. Interestingly, reactions occurred while all five children were being breast-fed (exclusively in four and mixed in one). CONCLUSIONS: Severe food allergic reactions can occur from exposure to minute quantities of allergen by skin contact or inhalation. Food allergy by a noningestant route should be considered in patients with the above characteristics.     

The influence of perennial allergic rhinitis on facial type and a pilot study of the effect of allergy management on facial growth patterns

Perennial rhinitis with an allergic component (PRAC) in association with chronic mouthbreathing has been thought to cause skeletal open-bite facial type and narrow transverse facial dimensions. The object of this study was to supply data for this theory and to determine if allergy management would alter the course of facial growth. When a group of children, aged 5 to 10 years, with PRAC was compared with a matched control sample, a significantly larger palatomandibular angle and lower anterior facial height were found for the PRAC group. Transverse cephalometric measurements showed significantly narrower bilateral orbital breadth, bizygomatic, and binasal dimensions (narrower face) of the PRAC patients compared with the control sample. A pilot study of twelve PRAC patients who received 2 1/2 years of allergy management revealed no significant dento-facial dimensional change. This study suggests that PRAC with chronic mouthbreathing can alter the development of the midface. Whether allergy therapy can prevent or change this is as yet uncertain.     

Primary dietary prevention of food allergy.

OBJECTIVE: To present research and clinical evidence on the use of primary dietary prevention in food allergy management. DATA SOURCES: We conducted MEDLINE searches for pertinent articles published between January 1986 and October 2001 with use of the following keywords or phrases: prevention and diet and allergy, food allergy and prevention, and dietary prevention and food allergy or allergens. Also included are information and commentary reflecting the authors' cumulative clinical experience in an allergy unit of a city hospital. RESULTS: We define as "proactive" those strategies centered on "success factors," such as the early postnatal environment, prolonged breast-feeding, and use of formula and probiotic supplementation, in contrast to earlier "prohibitionist" approaches to prevention of food allergy. These two approaches are not antagonistic and may even be synergistic. We introduce this distinction in light of epidemiologic evidence and out of concern about compliance and the quality of life for patients. CONCLUSIONS: Inasmuch as nutritional and immune maturation are implicated, the prohibitionist measures that are most effective in primary prevention of food allergy are exclusive breast-feeding for at least 6 months (for lifelong immunity and other benefits), delayed (after the sixth month) introduction of solid foods, and on-indication use of "hypoallergenic" formulas. Whether proactive strategies can be contemplated remains a debatable issue. Evidence for and against the scientific use of probiotics as well as microbiologic, epidemiologic, and clinical data are discussed. Review of published epidemiologic studies and randomized clinical trials is essential before planning dietary intervention or prevention.     

Utility of food-specific IgE concentrations in predicting symptomatic food allergy

BACKGROUND: The double-blind, placebo-controlled food challenge is considered the gold standard for diagnosing food allergy. However, in a retrospective analysis of children and adolescents with atopic dermatitis and food allergy, discrete food-specific IgE concentrations were established that could predict clinical reactivity to egg, milk, peanut, and fish with greater than 95% certainty. OBJECTIVE: The purpose of this investigation was to determine the utility of these 95% predictive decision points in a prospective evaluation of food allergy. METHODS: Sera from 100 consecutive children and adolescents referred for evaluation of food allergy were analyzed for specific IgE antibodies to egg, milk, peanut, soy, wheat, and fish by using the Pharmacia CAP System FEIA. Food-specific IgE values were compared with history and the results of skin prick tests and food challenges to determine the efficacy of previously established 95% predictive decision points in identifying patients with increased probability of reacting during a specific food challenge. RESULTS: One hundred children (62% male; median age, 3.8 years; range, 0.4-14.3 years) were evaluated for food allergy. The diagnosis of food allergy was established by means of history or oral food challenge. On the basis of the previously established 95% predictive decision points for egg, milk, peanut, and fish allergy, greater than 95% of food allergies diagnosed in this prospective study were correctly identified by quantifying serum food-specific IgE concentrations. CONCLUSION: In a prospective study of children and adolescents referred for evaluation of food allergy, previously established 95% predictive decision points of food-specific IgE antibody concentrations for 4 major food allergens were effective in predicting clinical reactivity. Quantification of food-specific IgE is a useful test for diagnosing symptomatic allergy to egg, milk, peanut, and fish in the pediatric population and could eliminate the need to perform double-blind, placebo-controlled food challenges in a significant number of children.     

What do asthmatics have to fear from food and additive allergy?

International studies report marked increases in the prevalence of food allergy, along with increases in hospital admissions and emergency presentations for severe allergic reactions due to foods. The prevalence of self‐reported food allergy is common, but generally exceeds that which can be verified from challenge studies, although nut allergies appear to be an important exception to this rule. Studies examining food allergy deaths suggest that those who die of food allergy usually have co‐existent asthma. Adolescents and young adults are at most risk, and adrenaline auto‐injectors are sub‐optimally used. Food chemical sensitivity is very commonly reported but not usually verified by challenge testing. However, the exception to this is sulphite sensitivity, which can elicit reproducible reactions in some. The increasing prevalence of severe food allergies and awareness of its risk in those with asthma demands an especially rigorous approach to the diagnosis and management of co‐existent food allergy and asthma, especially in young people who appear to be at most risk from death from severe food allergy. Cite this as: A. Gillman and Jo A. Douglass, Clinical & Experimental Allergy, 2010 (40) 1295–1302.     

Role and interpretation of total serum IgE measurements in the diagnosis of allergic airway disease in adults

BACKGROUND: While total IgE measurements are often used in clinical practice, it is unclear how they should be interpreted for the diagnosis of allergic disorders. We studied whether total IgE may be used to rule out or predict sensitization and whether there are age or gender differences. METHODS: ROC curves were assessed in subjects with asthma or allergy symptoms from a general population sample. We studied predictive values and likelihood ratios. At least one positive skin test (Phazet) or specific IgE measurement (CAP) served as reference. RESULTS: High negative predictive values, suitable to rule out sensitization, were not found. In younger subjects, high total IgE levels strongly increase the probability of sensitization. The relationship between monosensitization and total IgE was less strong, but meaningful positive likelihood ratios were found at higher levels of total IgE. The discriminating ability of total IgE was better in the age group 20-44 than 45-70 years and comparable in males and females. CONCLUSION: Total IgE is not useful to rule out sensitization to common inhalant allergens. High total IgE may indicate a high probability of sensitization and may be useful to decide whether further investigation is warranted in patients with negative specific allergy tests to a panel of common inhalant allergens.     

Hypogammaglobulinaemia secondary to cow-milk allergy in children under 2 years of age

Symptomatic hypogammaglobulinaemia in children younger than 2 years of age was studied to rule out a primary immunodeficiency. Thirty-four patients were referred to the Immunology Service to study the hypogammaglobulinaemia-associated clinical picture. Food allergy was documented in 10 patients by personal and familial history, presence of specific immunoglobulin E (IgE) and elevated total serum IgE levels. Coeliac disease and human immunodeficiency virus infection were also ruled out. Protein loss through stools was assessed by clearance of alpha1-antitrypsin (AAT). Serum immunoglobulin levels were determined by nephelometry and functional antibodies were studied by enzyme-linked immunosorbent assay. The cellular immune response was assessed by in vitro lymphocyte proliferation in response to mitogens and cell subsets were analysed by flow cytometry. In five patients of the 10 patients we suspected a protein loss through the mucosa. Four of these five patients showed an increased AAT and the other showed an extensive cutaneous lesion. Immunological studies revealed normal antibody function, in vitro lymphoproliferative responses and cell numbers in four of the 5 patients. One patient showed abnormally low numbers of CD4(+) T cells as well as a defective proliferative response to mitogens. After diagnosis of cow milk allergy, milk was replaced with infant milk formula containing hydrolysed proteins. Recovery of immunoglobulin values and clinical resolution were achieved. Hypogammaglobulinaemia during early childhood in some children may be secondary to cow milk allergy, and immunoglobulins and cells may leak through the inflamed mucosa. Resolution of symptoms as well as normalization of immunoglobulin values may be easily achieved by avoidance of the offending allergen.     

Genetic and environmental risk factors for the development of food allergy

PURPOSE OF REVIEW: To review recent clinical and experimental studies of genetic and environmental risk factors for the development of food allergy. RECENT FINDINGS: It may be true, although it is yet to be shown, that food allergies in early childhood are becoming more common and that the causes are the same as for later-developing respiratory allergies. The mother not only transfers 50% of her genes to her baby, but she is also the exclusive environment during gestation and continues to be a major environmental factor while breast-feeding her infant. Non-genetic maternal influences increasing the likelihood of food allergy include Caesarian section and high maternal age. Allergy to sesame seems to be increasing in children. This is possibly a consequence of increased use in processed foods. The search for dietary risk factors is not limited to allergenic foods, but may include other nutrients, for example excessive intake of vitamins. Two meta-analyses have seriously questioned the use of special infant formulas for allergy prevention. Novel prevention strategies, such as probiotic bacteria, have yet to be documented further. SUMMARY: The causes of food allergy are still unknown and no particular genes associated particularly with food allergy have been identified, although there is a strong association in general between genetic susceptibility to food allergy and that to IgE-mediated allergy. There are still no measures for general recommendation in order to prevent food allergy and no genes have been linked conclusively to disease. Further research concentrating on food allergy is obviously needed.     

Alcohol-induced rash caused by topical tacrolimus.

BACKGROUND: Topical treatment with tacrolimus may be complicated by ingestion-related flushing caused by consuming small amounts of alcohol, a reaction that can be mistaken for food allergy. OBJECTIVE: To increase awareness of a drug interaction with alcohol that can mimic food allergy. METHODS: We describe 3 patients who used topical tacrolimus, 2 with an atopic history and 1 without, who presented with a flushing reaction after ingesting alcohol. RESULTS: Cessation of topical tacrolimus use resolves the alcohol-related skin reaction. CONCLUSIONS: A careful history, including consideration of alcohol use, should be obtained in patients who use topical tacrolimus and present with new skin complaints, because these factors may be evidence of an avoidable drug interaction and not worsening of atopic disease or a food allergy.     

Reducing the need for food allergen challenges in young children: a comparison of in vitro with in vivo tests

BACKGROUND: Double-blind placebo-controlled food challenges (DBPCFC), the gold standard for the diagnosis of food hypersensitivity, are time-consuming and not without risk. We have recently reported skin prick test (SPT) weal diameters to cow's milk, egg and peanut above which infants and young children referred for investigation of suspected food allergy showed an adverse reaction on food challenge. We have termed these the "100% diagnostic SPT levels". In this study, we compare in vivo with in vitro measurement of IgE antibody levels to three common food allergens--cow's milk, egg and peanut--in infants and young children with suspected food allergy, in order to reduce the need for food challenges. METHODS: SPT and Enzyme Allergo-sorbent Test (EAST) (from 1992 to 1998) and CAP values (from 1999 to 2000) were performed in 820 children < 2 years of age with suspected allergy to cow's milk and/or egg and/or peanut. SPT levels previously shown to be diagnostic of challenge-proven allergy to cow's milk, egg and peanut were used as the "100% diagnostic SPT levels" and compared with EAST and CAP values associated with IgE food allergy according to the manufacturer's definition. RESULTS: McNemar's test showed a significant difference between the "100% diagnostic SPT levels" and positive EAST in identifying patients who did not require food challenge for cow's milk (P = 0.01), egg (P < 10-6) and peanut (P < 10-6), and a significant difference between the "100% diagnostic SPT levels" and positive CAP (P < 10-6) for egg and peanut but not cow's milk. Twenty-three per cent of food challenges which, based on the results of EAST and CAP, would have been necessary to confirm the diagnosis of food allergy were avoided by the use of the "100% diagnostic SPT levels" . CONCLUSION: The use of the "100% diagnostic SPT levels" compared with in vitro measurement of IgE antibody to cow's milk, egg and peanut reduces the need for food challenge in young children with suspected food allergy.     

Food antibodies in acute psychoses

Antibodies to a variety of foods, and in particular cereals, were measured in serum from 100 patients with acute psychoses and 100 elective surgical patients. For 13 out of 14 foods to which non-IgE antibodies were detected the schizophrenics had slightly more antibodies than the controls. There was an association between a possible secondary mania and the presence of IgE antibodies to wheat or rye. However, neither the schizophrenia nor the mania findings can be regarded as evidence for food allergy causing psychiatric disorder, since the immunological findings in both cases may represent consequences of the illnesses or their treatment, rather than causes of the illness.     

Component-resolved diagnostics in food allergy

PURPOSE OF REVIEW: The purpose of this paper is to review and discuss recent studies on component-resolved diagnostics in food allergy, involving panels of pure allergen molecules or arrays of peptides derived from allergen sequences, and to summarize the reporting of new food allergens during the past 2 years. RECENT FINDINGS: Several component-resolved diagnostic studies in food allergy suggest that the use of panels of allergen molecules may allow refined clinical information to be obtained on the likelihood or severity of an allergic food reaction and regarding diagnostic specificity. Further, in some studies the use of pure allergen molecules has led to a clearly higher sensitivity of the immunoglobulin E immunoassay compared with conventional allergen extracts. SUMMARY: While common diagnostic methods in allergy assess the presence or absence of allergen-specific sensitization, to date, no in-vitro or in-vivo test exists which exhibits full correlation with clinical food allergy. A multitude of recently reported findings and observations indicate that molecular analysis of allergen sensitization pattern may serve to enhance the clinical utility of immunoglobulin E antibody-based allergy diagnostics. Pure natural and recombinant allergen molecules as well as panels of synthetic peptides have been used for this purpose.     

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.     

Lupine-induced anaphylaxis in a child without known food allergy.

BACKGROUND: Lupine allergy is caused by ingestion of the flour of a plant called Lupinus albus, a member of the Leguminosae family. Lupine allergy has been described in adult patients previously known to have peanut allergy (cross-reactivity). OBJECTIVE: To describe the first case of an anaphylactic reaction caused by ingestion of lupine flour in a pediatric patient without a known peanut allergy. METHODS: Symptom assessment, nutritional history, and skin and blood tests. RESULTS: An otherwise healthy 8-year-old boy had nose and eye discharge followed by facial edema and difficulty breathing 30 minutes after eating an industrially prepared waffle containing eggs, sugar, and lupine flour. He had no history of food allergy and was eating a normal diet, including peanuts and other legumes. Results of skin prick tests using commercial extracts were positive to peanuts and negative to eggs, soy, and nuts; results of a prick-to-prick test using lupine flour were strongly positive (+ + + +). His total IgE level was 1,237 UI/mL. Specific IgE antibodies were positive to lupine seeds (20.8 kU/L) and peanuts (> 100 kU/L). CONCLUSIONS: To our knowledge, we describe the first case of an anaphylactic reaction after ingestion of lupine flour in a child without known allergy. In the case of peanut allergy or any anaphylactic reaction without evident cause, especially after industrially prepared food ingestion, lupine should be considered in the list of allergens tested. Lupine is increasingly used in industrially prepared food but is not regularly declared in the composition, leading to difficulties in allergen avoidance.     

Influence of a multidisciplinary paediatric allergy clinic on parental knowledge and rate of subsequent allergic reactions

BACKGROUND: Studies have demonstrated that families of children with food allergy have significant deficiencies in their knowledge of how to avoid allergen exposure and how to manage allergic reactions. This study aims to assess the impact of a multidisciplinary paediatric allergy clinic consultation on parental knowledge of food allergy and to determine the rate of subsequent allergic reactions. METHODS: Sixty-two subjects (<17 years) referred with food allergy were prospectively enrolled. Parental knowledge was assessed by questionnaire and EpiPen trainer. Families saw a paediatric allergist, clinical nurse specialist and dietician. Knowledge was reassessed after 3 months and rate of allergic reactions after 1 year. RESULTS: After one visit to the paediatric allergy clinic, there was a significant improvement in parental knowledge of allergen avoidance (26.9%, P < 0.001), managing allergic reactions (185.4%, P < 0.0001) and EpiPen usage (83.3%, P < 0.001). Additionally, there was a significant reduction in allergic reactions (P < 0.001). Children with egg, milk or multiple food allergies were more likely to suffer subsequent reactions. CONCLUSIONS: A single visit to a multidisciplinary allergy clinic considerably improves families' abilities to manage allergic reactions to foods with an accompanying reduction in allergic reactions. Young children with egg, milk or multiple food allergies were at greatest risk of further reactions.     

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.