Oral challenge tests for soybean allergies in Japan: A summary of 142 cases.

BACKGROUND: Soybeans are one of causative foods for infantile onset allergies in Japan. This study aimed to analyze the results of soybean challenge tests that were conducted over approximately 7 years at our institution. Using the test data, we sought to identify the responses and clinical profiles of patients with soybean allergies, and to investigate the relationship between the responses and soybean sensitization status. METHODS: Between July 2004 and May 2010, 142 cases (125 patients) underwent food challenge tests (100 g of silken tofu) for the diagnosis of soybean allergy or confirmation of their tolerance. The patients' characteristics, soybean sensitization status, and responses to the challenge tests were retrospectively evaluated. RESULTS: Among the subjects who underwent the soybean challenge test, the male/female ratio was 1.6 (87/55), and the mean age at the test was 2.8 ± 1.7 years. The positive rate for the challenge test was 38.7%. Induced symptoms were observed in the skin (81.8%), respiratory system (50.9%), and gastrointestinal system/mucosal membrane/anaphylaxis (12.7%). Intramuscular epinephrine was administered to all 7 patients who experienced an anaphylactic reaction. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic efficiency of soybean-specific IgE titers were low for predicting the responses to the challenge test. CONCLUSIONS: Soybean allergies were diagnosed in only 18% of the subjects with positive sensitization to soybeans. Therefore, soybean-specific IgE titers are not an effective predictor of a positive response to the challenge test.

The skin prick test is not useful in the diagnosis of the immediate type food allergy tolerance acquisition.

BACKGROUND: Some studies have been reported about positioning of SPT in the diagnosis of food allergy. On the other hand, it is not yet clear about the positioning of SPT in the diagnosis of tolerance acquisition of the immediate type food allergy. METHODS: The retrospective study had been conducted for 236 egg allergic children (51.3 months in mean), 127 milk allergic children (53.4 months), and 96 wheat allergic children (42.6 months). The retrospective analysis of serum nonspecific and antigen-specific IgE levels, SPT, and OFC had been conducted for each allergic patient. All OFC had been conducted to verify the acquisition of tolerance against eliminated food. RESULTS: The OFC was positive in 61 (25.8%) hen's egg allergies, 34 (26.8%) milk allergies and 33 (34.4%) wheat allergies. The greatest AUC for each allergen is as following; hen's egg for egg white specific IgE at 0.745, milk/histamine (wheal) index at 0.718, and wheat for wheal size at 0.597. For the predictive decision points, the highest accuracy rate was at 25.8% for an egg white wheal of 9.5mm, at 26.8% for a milk wheal of 9.5mm, and at 34.4% for a wheal of 6.5mm. CONCLUSIONS: As a result of this analysis, the diagnostic accuracy of SPT had not been satisfactory to judge the acquisition of tolerance in allergic children for eggs, milk and wheat. Therefore, this is not a strong evidence to testify the tolerance of the immediate type food allergy.

Measurement of Ara h 1-, 2-, and 3-specific IgE antibodies is useful in diagnosis of peanut allergy in Japanese children.

BACKGROUND: Food challenges are time-consuming, expensive, and not always possible to perform. Therefore, new tools to diagnose food allergy are desired. The aim was to evaluate IgE antibodies to peanut allergens in the diagnosis of peanut allergy in Japanese children using ImmunoCAP(®) and IgE immunoblotting. METHODS: The study included 2-13-yr-old consecutive patients (n = 57) referred to our specialist clinic for investigation of current peanut allergy using food challenge. All children had a previous doctor's diagnosis of peanut allergy and were on elimination diet. Serum samples were analyzed for IgE reactivity to peanut, recombinant (r) Ara h 1, 2, 3, 5, 8, and 9. IgE immunoblotting (n = 23) was performed using extracts from raw and roasted peanut. RESULTS: Twenty-six of the children failed (allergic group), and 31 passed the peanut challenge (tolerant group). The rAra h 2 ImmunoCAP test was superior in its ability to differentiate between children in the allergic and tolerant groups with a sensitivity and specificity of 88% and 84%, respectively (cutoff, 0.35 kU(A)/l). The combination of rAra h 1, 2, and 3 resulted in a higher specificity (94%) when IgE to all of them was the criteria for positivity. ImmunoCAP generally showed a good agreement with immunoblotting using both raw and roasted peanut for IgE reactivity to Ara h 1, 2, and 3. CONCLUSIONS: Measurement of IgE antibodies to rAra h 1, 2, and 3 is useful in the diagnosis of peanut allergy and in the investigation of reactions to raw and roasted peanut.

Utility of the peripheral blood basophil histamine release test in the diagnosis of hen's egg, cow's milk, and wheat allergy in children.

BACKGROUND: The diagnosis of food allergy (FA) is made by oral food challenge tests (OFCs) that occasionally produce serious symptoms in patients; therefore, whether to perform OFCs should be carefully considered. The utility of the histamine release test (HRT) in the diagnosis of childhood FA has not been fully examined. METHODS: Sixty-four subjects with suspected hen's egg allergy, cow's milk allergy (CMA), and wheat allergy (WA) were enrolled. The diagnosis of FA was made based on the outcomes of OFCs or a convincing history of symptoms after food ingestion within 6 months before or after sample collection. HRT was performed using an HRT Shionogi kit. The threshold of histamine release (HRT threshold), which was defined as the minimum concentration of food antigen to induce a 10% net histamine release, was analyzed in association with FA diagnosis. RESULTS: Receiver operating characteristic analysis showed that the HRT threshold was useful in the diagnosis of heated egg allergy (HEA), raw egg allergy (REA), CMA, and WA. We were able to determine the cutoff value for the HRT threshold in relation to outcomes of OFCs. The cutoff value was 6 ng/ml of egg white antigen in HEA and REA (p < 0.01), 40 ng/ml of milk antigen in CMA (p < 0.01), and 500 ng/ml of wheat antigen in WA (p < 0.05). The efficiency was 70.3% for HEA, 78.0% for REA, 77.6% for CMA, and 70.7% for WA. CONCLUSIONS: We conclude that the HRT threshold measurement for egg white, milk, and wheat antigen is related to outcomes of OFCs and is useful in determining when OFCs should be performed.

Basophil activation marker CD203c is useful in the diagnosis of hen's egg and cow's milk allergies in children.

BACKGROUND: The diagnosis of food allergy (FA) is usually based on oral food challenge tests (OFC). However, OFCs occasionally induce severe adverse reactions. CD203c expression on basophils is emerging as a potential diagnostic index. We evaluated whether CD203c expression on basophils would be a useful marker of OFC-associated symptoms in hen's egg and cow's milk allergies in children. METHODS: Seventy-one patients who had been diagnosed with FA based on OFCs or a convincing history of FA symptoms in the Department of Pediatrics, Sagamihara National Hospital, were recruited. CD203c expression was assessed after stimulation with antigens (egg white, ovomucoid, milk or casein) using allergenicity kits. The CD203c stimulation index (SI = the allergen-induced CD203c expression level divided by the baseline expression level) and the threshold of CD203c expression (the minimum concentration of antigen to induce CD203c SI >or=2) were analyzed in association with tolerance acquisition. RESULTS: For the CD203c SI, the areas under the receiver-operating characteristic curve were 0.72 for egg white, 0.82 for ovomucoid, 0.84 for milk and 0.67 for casein. The positive predictive value for the threshold of CD203c expression was 94.7% for egg white, 100% for ovomucoid, 85.7% for milk and 75.0% for casein. CONCLUSIONS: Assessment of food antigen-induced CD203c expression on basophils is useful to determine if children will outgrow FA as well as in decision making regarding whether or not to perform OFCs.

Associations of functional NLRP3 polymorphisms with susceptibility to food-induced anaphylaxis and aspirin-induced asthma.

BACKGROUND: NLR family, pyrin domain containing 3 (NLRP3), controls the activity of inflammatory caspase-1 by forming inflammasomes, which leads to cleavage of the procytokines IL-1beta and IL-18. Recent studies have shown associations of human NLRP3 polymorphisms with susceptibility to various inflammatory diseases; however, the association with allergic diseases remains unclear. OBJECTIVE: We sought to examine whether NLRP3 polymorphisms are associated with susceptibility to food allergy, food-induced anaphylaxis, and aspirin-induced asthma (AIA). METHODS: We selected 15 tag single nucleotide polymorphisms (SNPs) of NLRP3 and conducted association analyses of NLRP3 using 574 and 1279 samples for food allergy and AIA, respectively. We further performed functional analyses of the susceptible SNPs. RESULTS: Two NLRP3 SNPs (rs4612666 and rs10754558) were significantly associated with susceptibility to food-induced anaphylaxis (P = .00086 and P = .00068, respectively). The NLRP3 haplotype of the 2 SNPs also showed a significant association (P = .000098). We could confirm the association with susceptibility to another hypersensitivity phenotype, AIA (rs4612666, P = .0096). Functional analysis revealed that the risk alleles of rs4612666 and rs10754558 increased the enhancer activity of NLRP3 expression and NLRP3 mRNA stability, respectively. CONCLUSION: Our results indicate that the NLRP3 SNPs might play an important role in the development of food-induced anaphylaxis and AIA in a gain-of-function manner. Further research on the NLRP3 inflammasome will contribute to the development of novel diagnostic and therapeutic methods for food-induced anaphylaxis and AIA.

Usefulness of wheat and soybean specific IgE antibody titers for the diagnosis of food allergy.

BACKGROUND: Since the first suggestion of threshold values for food specific IgE antibody levels in relation to clinical reactivity, several authors have proposed different threshold values for different allergens. We investigated the relationship between wheat/soybean specific IgE antibody levels and the outcome of wheat/soybean allergy diagnosis in children of different ages. METHODS: A retrospective study was conducted in 536 children admitted consecutively to our clinic with the suspicion of wheat and/or soybean allergy. The children underwent an oral food challenge and blood samples for specific IgE measurement were obtained. RESULTS: The children who reacted to the oral food challenge had higher specific IgE titers to the specific allergen compared to the non-reacting group. The risk for reaction increased 2.33-fold (95% CI 1.90-2.87) for wheat and 2.08-fold (95% CI 1.65-2.61) for soybean, with increasing levels of specific IgE. A significant difference between the ages of subjects pertained only to wheat. CONCLUSIONS: We found a relationship between the probability of failed challenge and the concentration of IgE antibodies to both wheat and soybean. Age influences the relationship of allergen specific IgE levels to wheat and oral food challenge outcome. Younger children are more likely to react to low levels of specific IgE antibody concentration to wheat than older children.

[Single blind food challenge using dried food powder --2nd Report. milk].

AIM: We analyzed data obtained from cow's milk challenge with single-blind manner in our department. SUBJECTS AND METHODS: We have performed 83 cow's milk challenges in the hospital from 1995 to 2005, and patient profiles and results of the challenges were analyzed. RESULTS: Positive rate of cow's milk challenges were 44.6% (37/83), and evoked symptoms by cow's milk challenges were most frequently seen in skin, followed by respiratory tract, and gastrointestinal system. Cases of anaphylaxis were seen in 8.1%. Seventy six percentages of symptoms started within one hour after the challenge, and 56.8% among positive cases were medicated. Adrenaline was injected in 9 cases out of 37 positive challenge cases. And all anaphylaxis patients recovered. We performed 19 open challenges with heated-cow's milk among 37 positive cases, and only one negative case existed. When we compared profiles of negative cow's milk challenges and positive ones, significant higher rate on positive skin prick tests (SPT) against cow's milk and complication of bronchial asthma were recognized in positive group. Sensitivity of SPT was 97.3% and specificity was 17.4%. Sensitivity of IgE CAP-RAST was 100% and specificity was 15.2%. CONCLUSIONS: Single-blinded challenge tests were safe. And they were useful in judgment of the acquisition of oral tolerance in cow's milk allergy. It was only one case that effect of the heating un-matched in food provocation test results. Although we experienced fairly high prevalence of respiratory symptoms during cow's milk challenge tests, appropriate medication especially adrenaline introduction made our test safe enough.

[Single blind food challenge using dried food powder--1st report. Raw whole egg and egg yolk].

AIM: We have analyzed data of raw whole egg and egg yolk challenges performed in single-blinded manner. SUBJECTS AND METHODS: We have performed 92 whole egg challenges and 109 egg yolk challenges in admission from 1995 to 2005. RESULTS: The positive rate of whole egg challenges was 76.1%, and the most frequent symptoms seen during challenges involved gastrointestinal (GI) system, followed by skin, and respiratory system. The rate of anaphylaxis was 4.3%. Among 70 raw-egg positive cases, 62 heated-egg challenges were performed in open manner, which resulted in 18 negative cases (29%) against it. When we compared IgE CAP RAST against egg white between challenge positive cases and negative ones, IgE CAP RAST against egg white was significantly higher in positive group. With regards to yolk egg challenges, positive rate was 23.9%, and evoked symptoms were most frequently seen in skin, followed by GI system, and respiratory system. No case of anaphylaxis was observed. CONCLUSIONS: Single-blinded challenge tests against whole egg and egg yolk were useful for the diagnosis of pediatric egg allergy. IgE CAP RAST against egg white was useful when we considered timing of egg challenge tests. Among raw egg allergies, around 30% of patients could eat heated-whole egg. In order to improve egg allergy patients' quality of life, it is important to first introduce egg yolk challenges followed by heated-whole egg challenges, and finally raw-egg challenges, if it is necessary, in blinded manner.

[Prolonged type of food allergy].

OBJECT: Prevalence of food allergy is the most frequent during infancy, and it is gradually decreasing with age. We can not distinguish patients developing tolerance from those with persistent food allergy, therefore we are unable to advice patients accelerating the development of tolerance. To clarify the factors developing tolerance or intolerance, we conducted the following study. METHOD: Patients who were diagnosed as food allergy to hen's egg, or cow's milk or wheat in infancy by the definitive history of positive food allergic reactions or food provocation tests were recruited to this study. Patients were divided into two groups; one (prolonged group, n=27) is those who needed to eliminate some of the main offending foods even at the age of 6 years old and the other (tolerized group, n=37) is those who had released all main offending foods by the age of 6 years old. RESULT: The factors which distinguished the prolonged group from the tolerized group were the positive clinical history of the atopic dermatitis and its prolonged clinical course, past history of anaphylactic shock, and maximum number of offending foods in the past clinical history. The specific IgE against main antigens such as egg white, cow's milk and wheat in the tolerized group was lower compared to that in the prolonged group, whereas no significant difference was found in non specific IgE value, peripheral eosinophil counts, and specific IgE against other antigens. CONCLUSION: We could find the clinical factors discriminating food allergy patients against three major food allergen among children developing tolerance by the age of 6 years old form those without tolerance.