Positive Double-blind Placebo-controlled Food Challenge Research Articles

Predictive value of the sulfidoleukotriene release assay in oral allergy syndrome to celery, hazelnut, and carrot.

Patients sensitized to birch pollen frequently suffer from a food allergy to plant foods such as celery, carrots, or hazelnut. One of the main manifestations of birch pollen-related food allergy is the oral allergy syndrome. Skin tests and allergen-specific immunoglobulin (Ig) E determinations are poor predictors of such reactions when assessed by double-blind placebo-controlled food challenge (DBPCFC). To investigate whether a cellular test based on leukotriene release from basophils, the cellular antigen stimulation test in combination with enzyme-linked immunosorbent assay (CAST-ELISA), is predictive of pollen-related food allergy. Birch pollen-sensitized patients with positive DBPCFC to celery (n=21), hazelnut (n=15), and carrot (n=7) underwent skin tests along with determination of specific IgE and CAST-ELISA for the respective allergens. The results were compared with those of 24 birch pollen-sensitized patients with negative open food challenge to celery, hazelnut, and carrot. While skin prick tests had a sensitivity of 85%, 80%, and 29% for commercial extracts of celery, hazelnut, and carrot, respectively, prick testing with self-prepared extracts yielded sensitivities of 100%, 80%, and 100%, respectively. For specific IgE determinations, sensitivities were 71%, 73%, and 57%, respectively, and the respective specificities were 67%, 73%, and 60%. For CAST-ELISA with various sources and doses of allergens, the sensitivity varied from 71% to 95% for celery, 73% to 80% for hazelnut, and 43% to 86% for carrot. The respective specificities were 67% to 92%, 75% to 88%, and 77% to 91%. Analysis of the predictive value of CAST-ELISA with receiver operating characteristic curves showed that the results of the tests were more predictive of pollen-related food allergy than quantitative allergen-specific IgE determinations. CAST-ELISA is more specific than routine diagnostic tests for the diagnosis of pollen-related food allergy to celery, hazelnut, and carrot.

Determination of no-observed-adverse-effect levels and eliciting doses in a representative group of peanut-sensitized children

Current labeling practices for allergenic foods like peanut can be inadequate. For future regulatory and industry guidelines, information on no-observed-adverse-effect levels (NOAELs) and eliciting doses (EDs) for allergenic foods is necessary. To determine NOAEL and ED in a representative group of peanut-sensitized children, relate these data to history and sensitization, and evaluate the outcome of dietary management. From an overall eligible group of 96 peanut-sensitized children, a representative group of 27 was evaluated by questionnaires, skin prick test, determination of specific IgE, and double-blind placebo-controlled food challenge (DBPCFC) with peanut according to the international consensus protocol, with 9 doses ranging from 10 microg to 3 g peanut flour. Dietary management was evaluated over a 12-month period. Twenty-two children (81%) had a positive DBPCFC. The NOAEL in this group was 1 mg peanut flour, corresponding to 2 mg whole peanut. The ED for subjective symptoms (10 mg to 3 g) was significantly lower than for objective symptoms (100 mg to 3 g; P = .002). Severe reactions occurred only at high doses. EDs were not correlated to previous reactions by history, skin prick test, or specific IgE levels. All patients with a positive DBPCFC were advised to follow a strict diet. During the follow-up period, 10 patients had a less strict diet likely containing traces of peanut. In 3 cases, a mild reaction occurred with food products labeled "may contain peanut." The NOAEL in a representative group of children with peanut allergy was 2 mg. Dietary compliance in half of this group was inadequate.

Screening the allergenic repertoires of wheat and maize with sera from double‐blind, placebo‐controlled food challenge positive patients

Food allergy to wheat and maize is an increasing factor of deterioration of life quality, especially childhood and can, in rare cases, even induce anaphylaxis. Although omega-5 gliadin from wheat and maize lipid transfer protein have been characterized as major cereal allergens on the molecular level, the list of food allergens is far to be complete. To identify the IgE-binding repertoires of wheat and maize we screened respective cDNA libraries displayed on phage surface with sera from patients with a confirmed food allergy. The study included six patients with a positive double-blind, placebo-controlled food challenge (DBPCFC) to wheat, nine patients with a positive DBPCFC to maize, and six patients with anaphylactic reactions after ingestion of wheat. The enriched sequences encoding IgE-binding proteins showed heterogeneous repertoires for both, wheat and maize. The selected wheat repertoire yielded 12, the maize repertoire 11 open reading frames. Among these we identified allergens belonging to already characterized allergens families, such as gliadin, profilin and beta-expansin. Besides, we found novel proteins with high cross-reactive potential, such as thioredoxins, as well as sequences that had so far not been related to cereal allergy at all. The IgE-binding capacity of some selected proteins was evaluated in vitro and cross-reactivity was demonstrated by competition ELISA. With regard to the heterogeneity of the characterized sequences as well as to the biochemical nature of the new allergens detected we conclude that wheat and maize-related food allergy is more complex than so far anticipated.

Comparison of the allergenicity of Actinidia deliciosa (kiwi fruit) and Actinidia chinensis (gold kiwi)

Actinidia chinensis (gold kiwi) is a newly available fruit which has been shown to have in vitro immunoglobulin E (IgE) cross-reactivity with green kiwi. This is the first study to investigate clinical reactivity of gold kiwi. Five patients clinically allergic to green kiwi were investigated by skin test and double-blind placebo controlled food challenge (DBPCFC) with gold kiwi fruit. IgE-binding patterns of individual sera from the five challenged patients and a pool of sera from a further nine patients with kiwi allergy were compared in the two fruits by Western blotting. Cross reactivity of proteins in the two fruits was assessed by inhibition of immunoblots and by IgE enzyme-linked immunosorbent assay (ELISA) inhibition. Four of the five patients had a positive DBPCFC to gold kiwi. Western blotting showed marked differences in the allergen patterns of green and gold kiwi. However, inhibition of the immunoblots and ELISA assay reveals extensive inhibition of IgE binding to proteins in each fruit by the alternative species. Gold kiwi fruit is allergenic and patients allergic to green kiwi are at risk of reacting to the gold kiwi fruit. Despite having different protein profiles and IgE-binding patterns, the two species have proteins that extensively cross-inhibit the binding to IgE.

Response to intestinal provocation monitored by transabdominal ultrasound in patients with food hypersensitivity

ObjectiveOwing to lack of objective measures, the diagnosis of food hypersensitivity may be difficult. The aim of this study was to investigate whether the intestinal response to direct provocation in patients with food hypersensitivity could be recognized by ultrasound. Material and methodsThirty-two patients with chronic abdominal complaints, self-attributed to food hypersensitivity/allergy were included in the study. Via a nasoduodenal tube, the duodenal mucosa was challenged with the suspected food item dissolved in 10 ml water or saline. Using external ultrasound, the sonographic features (wall thickness and diameter of the duodenal bulb and jejunum, peristalsis activity and luminal fluid) were recorded before and during one hour after challenge. ResultsSonographic changes were observed after challenge in 14 (44%) of the 32 patients. A positive sonographic response (increased wall thickness, diameter, peristalsis and/or luminal fluid) was significantly related to a positive skin prick test (p=0.008) and a positive double-blind placebo-controlled food challenge (p=0.03). A significant correlation was found between provocation-induced symptoms and wall thickness of the duodenal bulb (r=0.50, p=0.004) or the jejunum (r=0.42, p=0.02). Intra- and interobserver variation of the tracing procedure showed low values. ConclusionsResponses of the proximal small intestines to direct provocation (swelling of the wall and exudation of fluid into the lumen) could be visualized by transabdominal ultrasound. This new provocation test could be helpful in the evaluation of patients with food hypersensitivity.

Patients with Subjective Food Hypersensitivity: The Value of Analyzing Intestinal Permeability and Inflammation Markers in Gut Lavage Fluid

Background/Aim: Subjective food hypersensitivity is prevalent in the general population. The aim of this study was to seek objective evidence of food hypersensitivity by analyzing intestinal permeability and inflammation markers in gut lavage fluid. Methods: Fifty-two patients with abdominal complaints self-attributed to food hypersensitivity were examined by skin prick test, serum IgE analysis, double-blind, placebo-controlled food challenge (DBPCFC), and intestinal lavage. The results were compared with those of 44 patients without food hypersensitivity. Neither the patients nor the controls had organic diseases that could explain their symptoms. Intestinal lavage was performed by administering 2 liters of isotonic polyethylene glycol (molecular weight 3,350 daltons) solution containing 50 µCi of [⁵¹Cr]EDTA through a nasoduodenal tube. The first clear fluid passed per rectum was collected and analyzed for histamine, eosinophilic cationic protein (ECP), tryptase, and calprotectin. The intestinal permeability was assessed by determining the 5-hour urinary excretion of [⁵¹Cr]EDTA. Calprotectin was also analyzed in native faecal samples. Results: The ECP concentration in gut lavage fluid was significantly higher in the patients than in the controls (p = 0.007), but the overlap between groups was large. Food hypersensitivity was confirmed by positive DBPCFC in only 4 patients. On average, histamine and ECP concentrations were high in these patients. Tryptase, intestinal permeability, and faecal and lavage calprotectin levels were normal. Conclusions: Very few patients had objective evidence of food hypersensitivity. Analyzing intestinal permeability and inflammation markers in gut lavage fluid did not contribute to the diagnosis, but further studies on histamine and ECP are warranted.

P0013 PP ABNORMALITIES IN CD8 FUNCTION IN NON-IGE FOOD ALLERGY: A NEW RELATIONSHIP?

Introduction: Non-IgE mechanism may also be involved in food allergy(FA)and we have been studying its immunopathogenesis and have demonstrated Th1/Th2 cytokines alterations associated with clinical entities afecting the gastrointestinal(GALT), bronquial(BALT)and skin(SALT)associated lymphoid tissue systems.(1,2,3)The objective of the present study is to describe a new immunologic alteration observed in patients with non-IgE mediated FA with GALT, BALT and SALT sistems manifestation related to very low CD8 lymphocytes. Methods: We investigated 8 patients (4 children and 4 adults) for FA with chronic symptoms of anorexia, diarrhea, abdominal pain, asthma, universal edema, urticaria and weight loss.The diagnosis of FA was made by double-blind placebo-controlled food challenge(DBPCFC).Immunologic studies of lymphocytes in peripheral blood was done and amino-acid based formula was introduced in the diet after the diagnosis. Results: The diagnosis of non-IgE FA was stablished by positive DBPCFC,negative IgE RAST test,normal IgE and eosinophyls in blood.Cytokines lineages shown normal intracellular Th1 pattern(IFN–y 8+/−2;IL-2 10+/−3) and normal Th2 pattern(IL-4 5,1+/−1;IL-5 0.8 +/− 0.6).All 8 patients shown abnormal CD8 in peripheral blood(CD8 absolute number mean 160 +/− 48) with normal CD4( mean 1568 +/− 344 ).Abnormal CD4/CD8 ratio over 6 was observed in all patients.After the diet all patients did well with normalization of the clinical picture. Challenge with common offending foods (milk, soy, meat, wheat and egg protein) reveal multiple allergies to all foods tested. After two years of follow-up the patients remain allergic to several foods and still in aminoacid based formula.Very low CD8 remain the unique immunologycal alternation in the lab tests in all the patients. Conclusion: These studies suggest that abnormality in CD8 function may play a role in non-IgE mediated FA as the unique immunological disturbance and more studies are necessary to clearly understend the basic immunologic mechhanisms.

A kinetic study in adults with food hypersensitivity assessed as eosinophil activation in fecal samples.

Immune-mediated food hypersensitivity affecting the gut is difficult to evaluate, and objective tools to diagnose local gastrointestinal (GI) inflammatory reactions are lacking. To determine whether allergic manifestations in adults with a history of food-related GI symptoms could be assessed in feces during symptomatic and non-symptomatic periods, using the surrogate markers, eosinophil cationic protein (ECP), eosinophil protein X (EPX) and myeloperoxidase (MPO). Thirteen subjects with food hypersensitivity-related GI symptoms, confirmed by a positive double-blind placebo-controlled food challenge (DBPCFC), were subjected to an open kinetic food challenge design for 6 weeks. Symptoms were recorded and scored during the 3-week study period and stool samples were obtained every day. The surrogate markers ECP, EPX and MPO were measured in the supernatants from feces samples. A significant increase in abdominal pain, distension and flatulence was observed during challenge, with a gradual decrease during elimination diet. Both between days and subjects, EPX levels were more frequently increased compared to ECP and MPO. Individuals with a history of a short duration of symptoms had significantly higher mean levels of EPX and MPO than those with a longer duration of symptoms. An overall increase in levels of eosinophil markers, in particular EPX, was observed in feces from patients with food-related GI symptoms. However, rather than being a tool to differentiate symptomatic from non-symptomatic periods, EPX might be used for detecting an ongoing clinical or subclinical chronic inflammation, that may have an impact on the patient's clinical course of GI symptoms.

Asthme et allergies alimentaires : à propos de 163 observations pédiatriques

The prevalence of food as a cause for asthma is not well known. The aim of this study was to define with standardized tests the incidence of food-induced asthma, the distribution of foods allergens in asthmatic children with food allergy. The study was carried on 163 asthmatic children with food allergy followed during average of 5.5 years. Asthma has been identified with pulmonary function tests (reversibility of FEV1 to bronchodilators) and food allergy has been documented by double-blind placebo-controlled food challenge (DBPCFC). Familial atopic disease was found in 148 children (90.7%). Inhalant sensitization was documented in 132 children (81%). Positive DBPCFC were observed in 250 of 385 challenges (65%) carried on these 163 children. The most frequent offending foods were, sometimes in association, peanut (30.6%), egg (23.1%), cow's milk (9.3%), mustard (6.9%), codfish (6%), shrimp (4.5%), kiwi fruit (3.6%), hazelnut (2.7%), cashew nut (2.1%), almond (1.5%), garlic (1.2%). Symptoms occurring during DBPCFC were cutaneous (143 cases, 59%), respiratory symptoms (58 cases, 23.9%), gastrointestinal symptoms (28 cases, 11.5%) and 15 anaphylactic shock (6.1%). Respiratory symptoms were oral allergy syndrome in 13 cases (5.3%), rhinoconjunctivitis in 15 cases (6.1%), asthma in 23 cases (9.5%). Only seven of these children had asthma only (2.8% of cases). The prevalence of asthma induced by food allergy is low. In our study, asthma induced by food allergy concerned 9.5% of cases and asthma alone was identified in only 2.8% of cases. We observed new food allergens associated with respiratory symptoms such as kiwi fruit, tree-nuts (hazelnut, cashew) and spices. Diagnosis relied upon data obtained from history, skin prick-tests and specific IgE. Oral food challenge is the corner stone of the diagnosis. Asthma induced by food allergens is potentially severe leading to prescribe to these patients a first aid kit with bronchodilators and epinephrine auto-injectors.

Identification of hazelnut major allergens in sensitive patients with positive double-blind, placebo-controlled food challenge results

Background: The hazelnut major allergens identified to date are an 18-kd protein homologous to Bet v 1 and a 14-kd allergen homologous to Bet v 2. No studies have reported hazelnut allergens recognized in patients with positive double-blind, placebo-controlled food challenge (DBPCFC) results or in patients allergic to hazelnut but not to birch. Objective: We characterized the hazelnut allergens by studying the IgE reactivity of 65 patients with positive DBPCFC results and 7 patients with severe anaphylaxis to hazelnut. Methods: Hazelnut allergens were identified by means of SDS-PAGE and IgE immunoblotting. Further characterization was done with amino acid sequencing, evaluation of the IgE-binding properties of raw and roasted hazelnut with enzyme allergosorbent test inhibition, assessment of cross-reactivity with different allergens by means of immunoblotting inhibition, and purification by means of HPLC. Results: All the sera from the patients with positive DBPCFC results recognized an 18- and a 47-kd allergen; other major allergens were at molecular weights of 32 and 35 kd. Binding to the 18-kd band was inhibited by birch extract, indicating its homology with the birch major allergen, and abolished in roasted hazelnut. The 47-kd allergen is a sucrose-binding protein, the 35-kd allergen is a legumin, and the 32-kd allergen is a 2S albumin. Patients with severe anaphylactic reactions to hazelnut showed specific IgE reactivity to a 9-kd allergen, totally inhibited by purified peach lipid-transfer protein (LTP), which was heat stable and, when purified, corresponded to an LTP. Conclusions: The major allergen of hazelnut is an 18-kd protein homologous to Bet v 1, and the 9-kd allergen is presumably an LTP. Other major allergens have molecular weights of 47, 32, and 35 kd. (J Allergy Clin Immunol 2002;109:563-70.)

Predictors of positive food challenge outcome in non–IgE-mediated reactions to food in children with atopic dermatitis

Background: Atopic dermatitis is frequently associated with food allergy. In general, clinically manifested food allergy is regarded as IgE mediated. However, there are some children with food allergy for whom IgE hypersensitivity cannot be proven. Objective: The aim was to evaluate the percentage of children with positive double-blind, placebo-controlled food challenge (DBPCFC) results but without any proof of IgE sensitization and to characterize this subgroup of children. Methods: Two hundred eight DBPCFCs were performed in 139 children (median age, 13 months) with atopic dermatitis and suspected food-related clinical symptoms. All children were subjected to skin prick tests (SPTs), determination of specific IgE, and atopy patch tests. Results: One hundred eleven (53%) of 208 oral food challenge results were assessed as positive. Positive challenge results were separated into 2 groups according to IgE positivity: negative SPT and negative specific IgE results in serum (group A, n = 12) and positive SPT, specific IgE, or both results in serum (group B, n = 99). The atopy patch test results; the distribution of early, late, or both clinical reactions; the age of the children; and the total IgE levels all showed no significant differences between the 2 groups. However, wheat challenge results were more often positive among the apparently non–IgE-sensitized children, and hen's egg challenge results were more often positive in the sensitized group (P < .05). Conclusion: Around 10% of positive DBPCFC results are not IgE mediated. Therefore not the proof of specific IgE but the suspicion of food-related symptoms should be the indication to perform oral food challenges, especially in the case of wheat. Otherwise, some children will not receive diagnoses for food allergy and be denied the benefits of a specific diet. (J Allergy Clin Immunol 2001;108:1053-8.)

Allergy caused by ingestion of persimmon (Diospyros kaki) : Detection of specific IgE and cross-reactivity to profilin and carbohydrate determinants

Background: Allergy to persimmon (Diospyros kaki) is very rare and not yet confirmed by means of double-blind, placebo-controlled, food-challenge (DBPCFC). Thus far, specific IgE to this fruit and cross-reactivity to pollen and other foods has not been determined. Objective: The objective was to confirm allergy to persimmon in 3 patients with an according personal history and to characterize allergens and cross-reactivity of specific IgE antibodies to pollen and food allergens. One patient reacted with pruritus, penis edema, urticaria, and asthma; the second reacted with nausea and vomitus; and the third reacted with rhinoconjunctivitis, asthma, and stomachache after ingestion of persimmon. Methods: Patients underwent skin prick testing with routine allergens, latex, persimmon, and other foods. Allergy to persimmon was confirmed by means of a DBPCFC. Specific serum IgE levels were measured with CAP-FEIA and the enzyme allergosorbent test (EAST) method. EAST and immunoblot inhibitions were carried out with persimmon; birch, grass, and ragweed pollen; latex; and N-glycans as inhibitors. Results: All patients had positive skin test responses, DBPCFC and specific IgE assays to persimmon. Blot and EAST inhibition assays revealed IgE to cross-reactive profilin in one patient and IgE to cross-reacting carbohydrate determinants in all patients. Conclusions: This is the first report on 3 cases of allergy to persimmon verified by means of DBPCFC and detection of specific IgE. The sensitization is due to cross-reactive profilin and carbohydrate determinants. (J Allergy Clin Immunol 2001;107:718-23.)

Celery allergens in patients with positive double-blind placebo-controlled food challenge

Background: Recently, for the first time, allergy to celery was confirmed by double-blind placebo-controlled food challenge (DBPCFC). Api g 1, Api g 4, cross-reactive carbohydrate determinants (CCD), and a 60 kDa allergen have been described as celery allergens. Objective: To get insights in IgE responses of patients with a positive DBPCFC to celery tuber (celeriac) compared with patients with a negative challenge test. Methods: Specific IgE to native and heated celery tuber and to recombinant Api g 1, the major celery allergen, were determined by enzyme allergosorbent test and immunoblotting. IgE binding to Api g 1, Api g 4, and CCD was confirmed by inhibition experiments that used recombinant Api g 1, recombinant Api g 4, pure N-glycans, and extracts of celeriac, lychee fruit, and pollens of birch, mugwort, and timothy grass as inhibitors. Results: Immunoblotting with sera from 22 patients with a positive DBPCFC to celeriac confirmed the presence of known allergenic structures: The major allergen Api g 1 (16 kDa) was recognized by IgE from 13 of 22 patients (59%). Another major allergen was CCD, determined by IgE reactivity in 12 of 22 patients (55%). Celery profilin, Api g 4, was recognized by IgE from 5 of 22 patients (23%). Conclusion: Our DBPCFC-positive patients exclusively presented IgE to known celery allergens, although the prevalences were slightly different than were previously reported. No obvious differences were found in patients with positive IgE antibody but negative challenge test. IgE binding to all 3 structures in celeriac extract was inhibited by birch pollen extract, whereas mugwort pollen extract could only inhibit IgE reactivity to Api g 4 and CCD. Inhibition experiments with a purified carbohydrate moiety clearly showed that the IgE epitope mannose-xylose-fucose-glycan (Manα1-6[Xylβ1-2]Manβ1-4GlcNAcβ1-4[Fucα1-3]GlcNAc) or a closely related structure is present in celeriac extract and is important in patients with clinical allergy to celery. (J Allergy Clin Immunol 2000;106:390-9.)

Hazelnut allergy: A double-blind, placebo-controlled food challenge multicenter study

Background: Tree nuts are a common cause of food allergy in Europe. However, few studies deal with real food allergy to hazelnuts in subjects believed to be allergic to this food. Objective: We sought to select subjects with a history of allergic reactions on ingestion of hazelnut and determine how many of these have true allergy by means of the double-blind, placebo-controlled food challenge (DBPCFC). Methods: Eighty-six subjects with a history of symptoms after hazelnut ingestion were recruited from 3 allergy centers (Milan, Zurich, and Copenhagen). All subjects underwent skin prick tests (SPTs) with aeroallergens and hazelnut, as well as having their specific hazelnut IgE levels determined. Diagnosis of clinical relevant food allergy was made on the basis of the DBPCFC. Results: Sixty-seven (77.9%) of 86 subjects had a positive DBPCFC result; 8 were placebo responders, and 11 were nonresponders. Of the 11 nonresponders, 4 had positive open-challenge test results. Of the DBPCFC-positive subjects, 87% also had positive skin test responses to birch pollen extract. Specific IgE determination for hazelnut (positive CAP response ≥0.7 kU/L [ie, class 2]) showed a sensitivity of 0.75, a positive predictive value (PPV) of 0.92, a specificity of 0.16, and a negative predictive value (NPV) of 0.05. Skin tests with commercial hazelnut extract produced a sensitivity of 0.89, a PPV of 0.92, a specificity of 0.05, and an NPV of 0.05. Skin tests with natural food produced a sensitivity of 0.88, a PPV of 0.94, a specificity of 0.27, and an NPV of 0.15. Conclusion: This study shows that hazelnut is an allergenic source that can cause real food allergy, as confirmed by DBPCFC. Skin and IgE tests demonstrated reasonable sensitivity and PPV but a very low specificity and NPV, thus implying that these should not be used to validate the diagnosis of food allergy to hazelnut. (J Allergy Clin Immunol 2000;105:577-81.)

Nivalenol and iwman kidney disease?

Current labeling practices for allergenic foods like peanut can be inadequate. For future regulatory and industry guidelines, information on no-observed-adverse-effect levels (NOAELs) and eliciting doses (EDs) for allergenic foods is necessary.To determine NOAEL and ED in a representative group of peanut-sensitized children, relate these data to history and sensitization, and evaluate the outcome of dietary management.From an overall eligible group of 96 peanut-sensitized children, a representative group of 27 was evaluated by questionnaires, skin prick test, determination of specific IgE, and double-blind placebo-controlled food challenge (DBPCFC) with peanut according to the international consensus protocol, with 9 doses ranging from 10 μg to 3 g peanut flour. Dietary management was evaluated over a 12-month period.Twenty-two children (81%) had a positive DBPCFC. The NOAEL in this group was 1 mg peanut flour, corresponding to 2 mg whole peanut. The ED for subjective symptoms (10 mg to 3 g) was significantly lower than for objective symptoms (100 mg to 3 g; P = .002). Severe reactions occurred only at high doses. EDs were not correlated to previous reactions by history, skin prick test, or specific IgE levels. All patients with a positive DBPCFC were advised to follow a strict diet. During the follow-up period, 10 patients had a less strict diet likely containing traces of peanut. In 3 cases, a mild reaction occurred with food products labeled “may contain peanut.”The NOAEL in a representative group of children with peanut allergy was 2 mg. Dietary compliance in half of this group was inadequate.

Food allergy in human immunodeficiency virus (HIV) infection.

Gastrointestinal complaints and pruritic skin conditions are common in patients infected with human immunodeficiency virus (HIV). Because atopic disorders such as drug allergy, asthma, and allergic rhinitis are apparently increased, we hypothesized that food allergy may also be more common in patients with HIV. The purpose of this study was to estimate the prevalence of food allergy in patients infected with HIV. Consecutive patients visiting our outpatient adult HIV clinic were screened for possible food allergy by use of a questionnaire. One hundred seventy-six patients responded. Sixty-two of these patients reported symptoms compatible with a possible food allergy. Followup of the 62 subjects was possible in 40. Thirty-one patients were skin tested for foods thought to produce reactions. Three patients (1.7%) described previous anaphylactic responses to specific foods and were therefore not skin tested or challenged orally. Six patients (3.4%) described very strong histories of food allergy but either refused or were too ill for testing. Twenty-nine of the 31 patients had negative skin tests. One of the two patients with a positive skin test to a suspected food also had a positive double-blind, placebo-controlled food challenge (DBPCFC). There was no correlation between CD4 cell count and likelihood of food allergy. Based on a strong history alone, the maximal estimated prevalence of food allergy in this group was 5.7% (10 of 176). By using the more strict criterion of positive DBPCFC, the prevalence of food allergy in this patient population was 0.57% (1 of 176). These results suggest that food allergy is an uncommon disease in patients with HIV infection with an estimated prevalence similar to that found in the general adult population. Our data do not suggest an obvious direct correlation between HIV infection and food allergy.

Distinct patterns of cow's milk allergy in infancy defined by prolonged, two‐stage double‐blind, placebo‐controlled food challenges

The clinical manifestations of cow's milk allergy (CMA) are highly variable, and challenges usually identify only immediate, IgE mediated reactions. To clearly identify CMA of immediate and delayed types using a two-stage, double-blind, placebo-controlled food challenge (DBPCFC), and to prospectively compare the clinical history and analyses of specific IgE antibodies to milk in predicting outcome of DBPCFC. A total of 69 patients (33 girls, 36 boys) were recruited for study based on a history highly suggestive of CMA and resolution of symptoms on a bovine protein-free diet. After skin-prick tests (SPTs) and search for allergen-specific serum IgE antibodies by enzyme allergosorbent test (EAST), a two-stage DBPCFC was performed over several days. Of 16 patients (mean age 36.9 months) classified as probable immediate reactors based on the history, 10 (62.5%) had a positive DBPCFC with similar patterns to historical adverse reactions (< or = 2 h after milk exposure). The other 53 (77%) patients (17.3 months) had a history of probable delayed type CMA presenting with predominantly gastrointestimal symptoms from 2 h and up to 6 days after milk exposure. Of these, 15 (28.8%) had a positive DBPCFC, again with a symptom pattern similar to the history. Sensitivity/specificity of SPT was similar to that of EAST for both immediate (70/83% and 62/83% respectively, NS) or delayed (0/97% and 0/97%) CMA confirmed by DBPCFC. Using our two-stage, prolonged DBPCFC, we clearly identified two groups of children with CMA, reflecting different pathogenesis of either immediate-type IgE-dependent, or delayed-type IgE-independent allergy. Although useful in immediate reactors, IgE antibody determination cannot predict the outcome of DBPCFC in delayed reactors. A thorough clinical history was the most helpful tool to predict the type of response in challenge positive patients.

614 Food allergy in human immunodeficiency virus (HIV) infection

Background: Gastrointestinal complaints and pruritic skin conditions are common in patients infected with human immunodeficiency virus (HIV). Because atopic disorders such as drug allergy, asthma, and allergic rhinitis are apparently increased, we hypothesized that food allergy may also be more common in patients with HIV. Objective: The purpose of this study was to estimate the prevalence of food allergy in patients infected with HIV. Methods: Consecutive patients visiting our outpatient adult HIV clinic were screened for possible food allergy by use of a questionnaire. One hundred seventysix patients responded. Sixty-two of these patients reported symptoms compatible with a possible food allergy. Followup of the 62 subjects was possible in 40. Thirty-one patients were skin tested for foods thought to produce reactions. Results: Three patients (1.7%) described previous anaphylactic responses to specific foods and were therefore not skin tested or challenged orally. Six patients (3.4%) described very strong histories of food allergy but either refused or were too ill for testing. Twenty-nine of the 31 patients had negative skin tests. One of the two patients with a positive skin test to a suspected food also had a positive double-blind, placebo-controlled food challenge (DBPCFC). There was no correlation between CD4 cell count and likelihood of food allergy. Based on a strong history alone, the maximal estimated prevalence of food allergy in this group was 5.7% (10 of 176). By using the more strict criterion of positive DBPCFC, the prevalence of food allergy in this patient population was 0.57% (1 of 176). Conclusion: These results suggest that food allergy is an uncommon disease in patients with HIV infection with an estimated prevalence similar to that found in the general adult population. Our data do not suggest an obvious direct correlation between HIV infection and food allergy. Ann Allergy Asthma Immunol 1997;78:209–12.

Identification of peanut agglutinin and soybean trypsin inhibitor as minor legume allergens.

Peanuts and soybeans are frequent causes of food hypersensitivity reactions in children. Sera from 12 patients with atopic dermatitis and a positive double-blind placebo-controlled food challenge to peanut and sera from 5 patients with atopic dermatitis and a positive double-blind placebo-controlled food challenge to soybean were used to identify and characterize specific legume allergens. Identification of a minor allergen from peanut and a minor allergen from soybean was accomplished using various physicochemical techniques. The peanut fraction, peanut agglutinin, isolated by anion-exchange chromatography and electrolution and confirmed by amino acid sequencing, bound IgE in only 50% of the peanut challenge positive patients. The soybean fraction, soybean trypsin inhibitor, identified by gel filtration and electroelution and confirmed by amino acid sequencing, bound IgE in only 20% of the soy challenge positive patients. The identification of these two known legume proteins as minor allergens should allow further immunologic and structural investigations to compare the major and minor legume allergens.

Egg Hypersensitivity and Measles-Mumps-Rubella Vaccine Administration

Because reports have described egg-sensitive individuals in whom anaphylaxis developed after measles vaccination, current recommendations include delaying administration of egg-derived vaccines until skin testing can be performed. Specifically, the 1988 Red Book recommends skin testing via scratch, prick, or puncture with 1:10 dilution of the vaccine and, if the result is negative, intradermal testing is suggested. The purpose of this study was to evaluate the likelihood of reaction to measles-mumps-rubella (MMR) vaccine in patients with documented egg sensitivity and to delineate the efficacy of skin-prick testing (SPT) to MMR as a predictor of hypersensitivity to the vaccine. Egg sensitivity was documented by initial SPT to egg and then, if possible, double-blind placebo-controlled food challenge (DBPCFC). Patients with a positive DBPCFC to egg or a history of anaphylactic egg sensitivity had a SPT with the MMR vaccine and then were given the MMR vaccine. Additionally, children with atopic dermatitis who had been previously proven egg sensitive via DBPCFCs were evaluated retrospectively for sensitivity to the MMR vaccine. Sixteen children with a history of egg sensitivity underwent SPT to egg, with a positive result 3 mm greater than the negative control found in 12 patients. Eight of these children had a positive DBPCFC to egg. The SPT to MMR vaccine was negative in all 16 children; vaccine administration followed with no resultant systemic problems. Three children had a local reaction at the site of injection. Twelve additional children with atopic dermatitis and egg sensitivity were reviewed. Each child had a positive SPT and DBPCFC to egg.(ABSTRACT TRUNCATED AT 250 WORDS)