Faculty Bibliography

BACKGROUND:Food allergy is the most common cause of anaphylaxis outside the hospital setting. OBJECTIVE:We sought to determine the rate, circumstances, and risk factors for repeated doses of epinephrine in the treatment of food-induced anaphylaxis in children. METHODS:Anonymous questionnaires were distributed to families of children with food allergies during allergy outpatient visits to a food allergy referral center. Demographic information, allergy and reaction history, and details regarding the last 2 anaphylactic reactions requiring epinephrine were collected. RESULTS:A total of 413 questionnaires were analyzed. Seventy-eight children (median, 4.5 years of age; range, 0.5-17.5 years) reported 95 reactions for which epinephrine was administered. Two doses were administered in 12 (13%) and 3 doses in an additional 6 (6%) reactions treated with epinephrine. Peanut, tree nuts, and cow's milk were responsible for >75% of reactions requiring epinephrine. Patients receiving multiple doses of epinephrine more often had asthma (P = .027) than children receiving a single dose. The amount of food ingested or a delay in the initial administration of epinephrine were not risk factors for receiving multiple doses. The second dose of epinephrine was administered by a health care professional in 94% of reactions. CONCLUSION/CONCLUSIONS:In this referral population of children and adolescents with multiple food allergies, 19% of food-induced anaphylactic reactions were treated with more than 1 dose of epinephrine. Prospective studies are necessary to identify risk factors for severe anaphylaxis and to establish rational guidelines for prescribing multiple epinephrine autoinjectors for children with food allergy.

Food-induced anaphylaxis is a steadily increasing problem in westernized countries and now represents the leading cause of anaphylaxis in the outpatient setting, particularly in children. Much of our knowledge of the pathophysiology of food-induced anaphylaxis comes from animal studies. Food anaphylaxis in humans is thought to be entirely IgE mediated. Several features appear to be unique to these reactions; factors such as exercise can lower the "threshold" for anaphylaxis in certain susceptible individuals. Different methods of thermal processing can modify the allergenicity of food proteins. Alteration of stomach pH can allow for incomplete digestion of food proteins, leading to increased absorption of intact food allergens. Low serum platelet-activating factor acetylhydrolase may predispose to fatal food-induced anaphylaxis. With a greater understanding of the pathophysiology of food-induced anaphylaxis, novel approaches not only to identify those at risk, but to treat and ultimately prevent food-induced anaphylaxis, are on the horizon.

Cow's milk protein allergy is the most common food allergy in infants and young children. It is estimated that up to 50% of pediatric cow's milk allergy is non-IgE-mediated. Allergic proctocolitis is a benign disorder manifesting with blood-streaked stools in otherwise healthy-appearing infants who are breast- or formula-fed. Symptoms resolve within 48-72 h following elimination of dietary cow's milk protein. Most infants tolerate cow's milk by their first birthday. Food protein-induced enterocolitis syndrome presents in young formula-fed infants with chronic emesis, diarrhea, and failure to thrive. Reintroduction of cow's milk protein following a period of avoidance results in profuse, repetitive emesis within 2-3 h following ingestion; 20% of acute exposures may be associated with hypovolemic shock. Treatment of acute reactions is with vigorous hydration. Most children become tolerant with age; attempts of re-introduction of milk must be done under physician supervision and with secure i.v. access. Allergic eosinophilic gastroenteritis affects infants as well as older children and adolescents. Abdominal pain, emesis, diarrhea, failure to thrive, or weight loss are the most common symptoms. A subset of patients may develop protein-losing enteropathy. Fifty percent of affected children are atopic and have evidence of food-specific IgE antibody but skin prick tests and serum food-IgE levels correlate with response to elimination diet poorly. Elemental diet based on the amino-acid formula leads to resolutions of gastrointestinal eosinophilic inflammation typically within 6 wk.

Food allergy has emerged as an important target for research on curative treatment and prevention, with most efforts focusing on peanut, cow's milk, and egg allergy. This article reviews the recent developments in the potential treatments for IgE-mediated food allergy using native and engineered recombinant food proteins.

Food allergy is defined as an immune system-mediated adverse reaction to food proteins. Class 1 food allergens are represented by peanut, egg white, and cow's milk; they are heat- and acid-stable glycoproteins that induce allergic sensitization via gastrointestinal tract and cause systemic reactions. Class 2 food allergens are homologous to proteins in birch tree pollen and class 2 food allergy develops as a consequence of respiratory sensitization to the cross-reactive pollen. Class 2 food allergens are very heat-labile and tend to induce reactions limited to oral allergy symptoms. In contrast, plant nonspecific lipid transfer proteins are resistant to heating and tend to induce systemic reactions. Analysis of IgE-binding epitopes with SPOT membranes revealed that cow's milk-, egg- and peanut-allergic subjects without IgE antibodies against certain sequential epitopes of the major allergens were more likely to achieve tolerance than subjects whose IgE antibodies were directed against those epitopes. Subsequently, peptide microarray showed a correlation between reaction severity and the intensity of IgE binding and the number of epitopes recognized of patients' immune responses against peanut allergens. Taken together, these data suggest that the epitope recognition pattern and intensity of IgE binding are important determinants of severity and duration of food allergy.

BACKGROUND:Physicians who practice alternative medicine often prescribe bee pollen as a food supplement and a treatment for various ailments. OBJECTIVES/OBJECTIVE:To determine the qualitative and quantitative composition of bee pollen and to investigate the cutaneous reactivity of atopic patients to bee pollen extracts. METHODS:The absolute number of pollen grains per gram of bee pollen was calculated, and morphologic identification of the botanical family was performed. Five extracts of bee pollen were prepared for skin prick testing, according to standard methods. Two hundred two volunteers participated in the study; 145 were atopic patients with respiratory allergy. The remaining 57 were healthy volunteers or nonatopic patients and served as a control group. All participants underwent skin prick testing with a standard battery of 6 aeroallergens (olive, grasses mix, Parietaria, mugwort, Dermatophagoides pteronyssinus, and Dermatophagoides farinae) and with all homemade bee pollen extracts. RESULTS:All samples of bee pollen contained Oleaceae pollen in high concentrations. Small amounts of anemophilous pollen (Compositeae, Chenopodiaceae) were detected in various samples. A strong positive correlation was observed between cutaneous reactivity to bee pollen extracts and olive, grasses, and mugwort. CONCLUSIONS:Bee pollen contains a large amount of pollen, which belongs to various allergenic families of plants. Bee pollen retains its allergenic potential as demonstrated by strong cutaneous responses to bee pollen extracts observed in atopic patients in contrast to nonatopic subjects. Regarding pollen allergic individuals, further studies are needed to evaluate the safety of ingesting large amounts of bee pollen.

BACKGROUND & AIMS/OBJECTIVE:Secreted immunoglobulins play an integral role in host defense at mucosal surfaces, and recent evidence shows that IgG can participate in antigen sampling from the intestinal lumen. We examined whether IgE also could facilitate transepithelial antigen sampling. METHODS:Stool samples from food-allergic patients undergoing oral food challenge were analyzed for CD23 and food-specific IgE. CD23 isoform expression on primary human intestinal epithelial cells (IEC) was analyzed by polymerase chain reaction. The role of CD23 isoforms in transcytosis of antigen and IgE-antigen complexes was assessed using polarized human T84 cells retrovirally transfected with CD23a or CD23b. RESULTS:CD23 was expressed constitutively on IECs, and food-allergic patients had increased levels of soluble CD23 and food-specific IgE in the stool after challenge. CD23a, but not CD23b, was expressed by primary human IECs. We show in transcytosis assays that CD23a, but not CD23b, acts as a bidirectional transporter of IgE. In addition, specific IgE facilitated the uptake of antigen from the apical surface of an epithelial monolayer by diverting antigen from delivery to lysosomes. Finally, delivery of antigen-IgE complexes across the epithelial barrier could induce the degranulation of rat basophil leukemia cells transfected with the human high-affinity IgE receptor. CONCLUSIONS:These studies show that CD23a is expressed normally on human IECs, and in the presence of IgE can function as an antigen-sampling mechanism capable of activating subepithelial mast cells. IgE may serve as a secretory immunoglobulin that in concert with CD23 participates in food-induced pathophysiology of the gastrointestinal tract.

BACKGROUND:Levels of IgE antibody to egg white of greater than 7 kIU/L are highly predictive of clinical reactivity to egg, and lower levels often require evaluation with oral food challenge (OFC) to establish definitive diagnosis. OFCs have inherent risks, and diagnostic criteria indicating high likelihood of passing would be clinically useful. OBJECTIVE:We sought to determine whether the size of the skin prick test (SPT) to egg white adds diagnostic utility for children with low egg white-specific IgE antibody levels. METHODS:A retrospective analysis of clinical history, egg white-specific IgE antibody levels, SPT responses, and egg OFC outcomes was performed. RESULTS:Children who passed (n = 29) egg OFCs and those who failed (n = 45) did not differ significantly in age, clinical characteristics, or egg white-specific IgE levels. There were, however, significant differences between both egg white SPT wheal response size and egg/histamine SPT wheal index. Children who failed egg OFCs had a median wheal of 5.0 mm; those who passed had a median wheal of 3.0 mm (P = .003). Children who failed egg OFCs had a median egg/histamine index of 1.00; those who passed had a median index of 0.71 (P = .001). For egg white-specific IgE levels of less than 2.5 kIU/L, an SPT wheal of 3 mm or an egg/histamine index of 0.65 was associated with a 50% chance of passing. CONCLUSION/CONCLUSIONS:In children with low egg white-specific IgE levels, those with smaller SPT wheal responses to egg were more likely to pass an egg OFC than those with larger wheal responses. The size of the egg white SPT response might provide additional information to determine the timing of egg OFC. CLINICAL IMPLICATIONS/CONCLUSIONS:The size of the egg white SPT wheal response might provide the clinician with additional information to determine the timing of egg OFC in children with low egg white-specific IgE antibody levels.

Food allergy encompasses a variety of immune-mediated adverse reactions to foods. IgE-mediated, cell-mediated, and mixed-mechanism food allergy disorders are recognized. Over the past 2 decades, the prevalence of food allergy doubled and its phenotypic expression increased in Westernized societies. Major food allergens have been identified for many common foods. Laboratory diagnosis of food allergy relies heavily on the detection of food-specific IgE antibodies, but novel approaches include tests for T-cell-mediated disorders and tests for prediction of tolerance. OFC remains the diagnostic standard for food allergy. Management of food allergy focuses on avoidance of the offending foods, nutritional support, and prompt recognition and treatment of acute food allergic reactions. Anti-IgE monoclonal antibody is the first potential therapy for food allergy that is under-going testing in clinical trials.