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A 14-year-old girl presented to our hospital with food-dependent exercise-induced anaphylaxis (FDEIA), possibly caused by rice. Despite experiencing four previous episodes of suspected FDEIA, she did not seek medical attention at her own discretion. On the fifth occurrence of symptoms, the general practitioner suspected FDEIA and referred the patient to our hospital. The only common factor in all five episodes was the consumption of rice, leading to the examination of the patient under suspicion of FDEIA caused by rice. Skin prick test results were positive for bran and polished rice, and exercise after consumption of polished rice resulted in anaphylaxis. Therefore, we diagnosed FDEIA caused by polished rice. Immunoblotting confirmed the presence of immunoglobulin E reacting with 14-16kDa rice bran protein in the patient's serum. The immunoblot inhibition test suggested that the rice bran protein to which the patient's serum reacted was also present in polished rice and no wash rice. As the patient may experience FDEIA after ingestion of no wash rice or rice flour, she was advised to eliminate these from her diet, treating them similarly to brown rice or polished rice.

Background: The purpose of this study was to compare the antigenicity of Bonlact ® i (BL) with that of defatted soy protein (SP) and soy protein isolate (SPI), which is the original source of BL, using sera from patients with soybean allergy., Methods: Proteins were extracted from SP, SPI, and BL using PBS. Proteins in each sample were analyzed for antigenicity using inhibition ELISA with SP-specific IgE (sIgE), SDS-PAGE, and immunoblotting. Sere from patients with soybean allergy confirmed by an oral food challenge (OFC) (n=6, OFC + Pt), and from patients who were positive for soy-sIgE without symptoms ( n = 7, sIgE + Pt) were used for these assays. The cross-antigenicity of SP and BL with cow's milk (CM) proteins was also analyzed in the sera from patients with CM allergy using inhibition ELISA., Results: SDS-PAGE showed that the proteins in BL produced a smear-like band in the low-molecular-weight region compared with that in SP and SPI. Inhibition ELISA against SP-sIgE showed that BL had a significantly lower inhibition rate than that of SP in both OFC + Pt and sIgE + Pt. Immunoblotting analysis showed that the bands of BL were thinner than those of SP and SPI. Additionally, SP and BL showed no cross-antigenicity with CM proteins., Conclusion: The proteins in BL was partially digested, and its antigenicity was lower than that of SP and SPI.

Background: There is reportedly a difference in the diameter of the skin reaction induced by different types of skin prick test (SPT) devices. We compared the SPT diagnostic accuracy and wheal size between a Bifurcated Needle ® (BN) and SmartPractice ® Prick Lancet (PL), which are commercially available in Japan., Methods: An SPT was performed on 15 adults with and 10 without subjective symptoms of cedar pollinosis who wished to be examined for Japanese cedar pollen (JCP) sensitization. The SPT was performed blindly with a BN or PL with 10mg/ml of histamine dihydrochloride, 50% glycerosaline control, and JCP extract solution (TORII PHARMACEUTICAL CO., LTD., Tokyo, Japan). The wheal sizes induced by the BN and PL were then compared. The JCP-specific IgE antibody titer was measured to compare the sensitivity and specificity of the SPT., Results: Histamine wheal diameters were 6.0 (5.5-6.5) mm by BN and 6.0 (5.5-6.5) mm by PL (p=0.67), and none of the negative control solutions induced wheal. The respective sensitivity and specificity for cedar sensitization were 100% and 86% for BN, 100% and 79% for PL, and the areas under the ROC curve were 0.72 and 0.69 (p=0.32)., Conclusion: The diagnostic accuracy of cedar pollen extract based on specific IgE-JCP sensitization and the diameter of the wheal produced by a BN and PL were considered equivalent.

Background: No nationwide epidemiological survey of anaphylaxis in Japan has been conducted. The aim of this study was to elucidate the triggers and treatment of anaphylaxis in Japan., Methods: We prospectively collected clinical information on the triggers and treatment of patients who developed anaphylaxis or were admitted to the emergency room with anaphylaxis in the training and teaching facilities of the Japanese Society of Allergology between February 2015 and October 2017., Results: Seventy-nine of 451 facilities (18%) participated in the study, and a total of 767 patients (under 18 years, 73%; in-hospital, 7%) were enrolled. The most common triggers were food (68%), drugs (12%), food-dependent exercise-induced anaphylaxis (5%), insects (4%), and oral immunotherapy (3%), with drugs being the most common in-hospital trigger and food being the most common out-of-hospital trigger. The intramuscular injection of adrenaline in medical institutions accounted for 38% of cases, 10% of which required multiple doses. The rate of use of adrenaline self-injections in out-of-hospital cases was 12%., Conclusion: The present study revealed the most common triggers and treatment for anaphylaxis in Japan. Self-management at the onset of anaphylaxis and adrenaline administration as the initial treatment may be insufficient. Therefore, it is necessary to thoroughly instruct patients and educate physicians regarding anaphylaxis.

A 12-year-old girl experienced anaphylactic shock and respiratory failure immediately after eating 4 pieces of takoyaki made at home. We suspected pancake syndrome because of the three reasons: First, the patient had a history of bronchial asthma and allergic rhinitis without any history of food allergies; Second, takoyaki flour that had been stored at room temperature for one month after opening the package had been used; and Third, both the specific IgE (ImmunoCAP ® method) of Dermatophagoides farinae and Dermatophagoides pteronyssinus were found to be above the detection limit. Since the suspected flour had been discarded, a specimen of tako yaki was examined microscopically and 430 mites/g were identified. Although only 21.1ng/g of Der f 1 was detected by an ELISA, this amount was less than expected, based on the number of mites that had been observed. The decrease in the antigenicity of mite allergens due to heating and reducing agents, and the insolubilization of mite allergens due to disulfide bonds between the mite allergens and gluten were thought have made it difficult to identify mite antigens by ELISA.When pancake syndrome is suspected, and the flour that is thought to have caused the condition is difficult to obtain, microscopic identification of mites in cooked food should be considered.

Background and Purpose: The principal aim of this study was to clarify the clinical profile of pediatric patients with fruit allergies., Subjects and Methods: We assigned 265 pediatric patients with fruit allergies who were receiving outpatient treatment at Aichi Children's Health and Medical Center and 32 who underwent kiwi or banana oral food chal- lenge (OFC) test to an oral symptom group or a systemic symptom group and retrospectively examined their clinical profiles and prognosis from their medical records., Results: The most common cause of fruit allergy was kiwi (139 patients, 21% of all patients). Watermelon had the highest oral symptom induction rate (97%), whereas banana had the highest systemic reaction induction rate (46%). In the oral symptom group, the prevalence of hay fever was 54% and 66% of patients showed aller- gic reaction to multiple fruits. In contrast, in the systemic symptom group, the prevalence of pollen allergies was 24% and 77% of patients showed allergic reaction to a single fruit only. The results revealed that 65% of patients allergic to bananas had infant-onset allergy and seven among 20 patients were confirmed acquisition of tolerability by the OFC test., Conclusion: Our data suggest that there is a difference in the clinical profile and disease type between patients with oral symptoms and those with primarily systemic symptoms. It is important to differentiate between these patients for accurate diet guidance, safety management, and prognosis estimation.

Background: This study aimed to evaluate the clinical accuracy of specific IgE (sIgE) to Ara h 2 in the diagnosis of peanut allergy (PA). We also investigated the prevalence of complications with other nut allergies in PA patients., Methods: The Ara h 2-sIgE titer was examined in patients with positive results for sIgE to peanut from April 2014 to March 2015. The presence or absence of PA was diagnosed based on an oral food challenge or a convincing clinical history. The characteristics of 217 patients (including 90 PA patients) were retrospectively evaluated., Results: At ≥0.35U A /mL, Ara h 2 showed 85.6% sensitivity in the diagnosis of PA. At the clinically-designated positive cut-off value (≥4.0U A /mL), the positive predictive value was 93.1% and the specificity was 96.9%. However, the Ara h 2-sIgE levels were not correlated with the threshold dose or the severity of the symptoms that were provoked in the peanut challenge (n=42). Nine (10%) of the PA patients also had allergies to other tree nuts., Conclusion: The re-evaluation of the clinically-designated positive Ara h 2-sIgE cut-off value revealed that the cut-off value was appropriate. The differential diagnosis of tree nut allergies was suggested to be important in PA patients.

Background: Food processing causes decomposition, denaturation or polymerization of protein, which may alter an allergic reaction. This study aimed to investigate the insolubility and alteration of wheat allergens in processed foods and the reactivity to patient sera., Methods: We extracted proteins from wheat flour, udon and bread using different extracts and conducted SDS-polyacrylamide gel electrophoresis. IgE-immunoblotting was also conducted using sera from children with wheat allergy., Results: Soluble protein was extracted from wheat flour, and gluten fractions were also extracted by adding SDS. However, no proteins were able to be extracted from udon or bread witout severing the disulfide bonds under reducing condition. Only trace amounts of protein were detected in the water after boiling udon noodles. The reactivity of IgE antibody to the extracted protein did not differ among the different processed food types., Conclusions: Wheat allergens became strongly insolubilized after gluten formation and heating. However, the reactivity of IgE antibody to each allergen was not affected by food processing. Further studies are needed for the effects on clinical symptoms.

Background: We evaluated the clinical significance of the spontaneous histamine release ratio (SHR/T) and low responders in the automated basophil histamine release test (AllerportⓇ HRT)., Methods: This study analyzed the outcomes of 101 oral food challenges (OFC) with egg, milk or wheat (challenge-positive: n=79) in relation to the SHR/T. The traditional HRT low responders (n=27) were separated into two groups:"LOW"responders (n=10), who showed a ≥10% concentration-dependent maximum histamine release in response to the anti-human IgE stimulation, and"NON"responders who did not fulfill the criteria (n=17)., Results: Among the 34 patients with ≥20% SHR/T, 32 patients (94%) had a positive OFC with a low threshold dose which provoked severe symptoms. Among the"LOW"responders, four cases showed ≥10% allergen-specific maximum histamine release. On the other hand, concentration-dependent histamine release was not seen in the"NON"responders, suggesting the basophil function was not detected in this subgroup., Conclusion: The present study suggested that SHR/T could be an indicator of basophil activation and hypersensitivity in vivo. We also suggested that significant basophil functions might be detected among the "LOW"responders, but not among the"NON"responders.

Wheat-dependent exercise-induced anaphylaxis (WDEIA) is often reported in adults for whom the specific IgE to ω-5 gliadin can be a useful diagnostic test. However, few cases of WDEIA in children have been reported. We herein report six cases (aged 7-16 years) of children with WDEIA, who had no clinical history of immediate-type wheat allergy but who were diagnosed by a wheat ingestion + exercise provocation test. The specific IgE to wheat ranged <0.35-3.49 (median 1.64) UA/ml. Skin prick tests using wheat extract were performed on 3 patients who showed either a negative or low specific IgE titer to wheat, and all of them resulted in negative findings. The specific IgE to ω-5 gliadin was below the detection limit in all cases. Aspirin-supplemented provocation tests were performed to 4 cases who had negative results in the wheat + exercise test. All of these resulted in a positive reaction, and two of them provoked the occurrence of anaphylactic shock, which was relieved by the intramuscular injection of adrenaline. WDEIA in children cannot be ruled out by serological tests alone. On the other hand, severe symptoms might be provoked by the provocation test. Therefore, a safe procedure is warranted for the diagnosis of WDEIA in children.

Purpose This study aimed to evaluate the utility of the Allerport® HRT in the diagnosis of hen's egg allergy. Method We enrolled 51 subjects who underwent the Allerport® HRT before an oral food challenge (OFC) consisting of heated egg. Blood samples were collected within three months prior to OFC to measure histamine release (HR) and specific IgE antibody titers. We examined whether the Allerport® HRT was useful as a means of diagnosing hen's egg allergy and predicting severity of induced symptoms. Of 51 subjects, three whose OFC results were not valid**1** and 13 who were classified as "low responders" to the Allerport® HRT (%HR due to anti-IgE below 20%) were excluded. Of the remaining 35 subjects (average age: 4 years), 23 showed positive reactions to the OFC. Quantities of histamine released in spontaneous HR and egg white (EW)- and ovomucoid (OVM)-induced HR were significantly higher in patients with positive reactions. In our receiver operating characteristic analysis, the area under the curve for %HR against 6 ng/ml of EW was 0.9601 and that against 3 ng/ml of OVM was 0.9022. The cutoff value was 15.0% for EW and 3.7% for OVM. The sensitivity was 95.7% for EW and 91.3% for OVM, and the specificity was 83.3% for EW and 58.3% for OVM. %HR correlated well with the severity of induced symptoms in the OFC. Conclusion Allerport® HRT is useful for the diagnosis of hen's egg allergy, and may also aid in predicting the severity of induced symptoms.

Background: An original symptom score sheet named "Anaphylaxis Scoring Aichi (ASCA)" was created to quantitatively determine the severity of allergic symptoms provoked in an oral food challenge., Methods: ASCA lists and sorts subjective and objective symptoms into five organs (respiratory, skin-mucosal, gastrointestinal, psycho-neurological and cardiovascular). The organ scores were given (0 to 60 points) in accordance with the severity of each symptom. The total score was defined as the sum of the highest 5 organ scores (maximum 240 points) observed throughout the course of an OFC. This study evaluated the ASCA score in 253 cases of a positive food challenge (age 1-16 years, mean 5.3±3.2 years) conducted from April to August 2011 in our institute. The results were compared to the modified anaphylaxis grading presented in the Japanese Pediatric Guideline for Oral Food Challenge Test in Food Allergy 2009. At the same time, we evaluated the indications of symptomatic treatment using ASCA score., Results: The total score closely correlated with the anaphylaxis grading, but there was a wide range of overlap between grade 2 and grade 3. All cases with a total score≥60 points were equivalent to grade 4 or 5, and that were consisted of three or more organ symptoms. These severe cases contained respiratory or skin/mucosal symptoms, and despite the early induction of initial therapy, the symptoms became worse., Conclusion: ASCA is therefore considered to be a useful tool for use in an oral food challenge test.

Objective: To reveal the clinical utility of an IgE test specific to ω-5 gliadin in the diagnosis of immediate-type wheat allergy., Methods: We detected ω-5 gliadin-specific IgE in sera from all patients examined for wheat-specific IgE in our allergy clinic between January and October, 2008. The diagnostic value of the test was analyzed against the true diagnosis of wheat allergy based on oral wheat challenge or convincing clinical history. Subjects comprised 233 patients (median age, 3.6 years), 59 patients were diagnosed with wheat allergy, and 174 were judged to have no wheat allergy., Results: The prevalence of being diagnosed as wheat allergy was 68% in the patients with CAP score 2 to ω-5 gliadin IgE (n=31), and 87% in those with CAP score 3 (n=15). All of the 3 patients with CAP score 4 or more were wheat allergic. However, 24% of patients with wheat allergy showed negative results (<0.35 UA/ml). According to the data, we proposed the probability curve of ω-5 gliadin-specific IgE., Conclusions: IgE testing specific to ω-5 gliadin can offer a useful clinical marker for the diagnosis of immediate-type wheat allergy. But the data should always be evaluated with wheat-specific IgE titers, because of the low clinical sensitivity to detect the patients with wheat allergy.

Background: We have evaluated the prognosis of milk allergy and the related factors., Methods: Patients with milk allergy (n=60) who had initially visited our hospital before 2 years old were recruited for the chart review. The ability of milk intake (> 30 ml) at the age of 5 years and the related clinical factors were evaluated., Results: There were 33 patients (55%) who remained allergic to milk (allergic group) and 27 patients (45%) who could consume at least 30 ml of milk (small amount of milk intake group) by the age of 5 years. The small amount of milk intake group had a history of isolated skin symptoms after ingestion of milk more frequently than the allergic group. On the other hands, the allergic group experienced significantly higher rate of respiratory and gastrointestinal symptoms. Milk-specific IgE antibodies were examined repeatedly in each patient, and the IgE titers were significantly decreased by age in the small amount of milk intake group. In the allergic group, however, the maximum milk-specific IgE titers in each patient were significantly higher than those in the small amount of milk intake group, and after significant increase from the age of 0 to 1 years, the IgE titers did not decrease until the age of 3 years., Conclusions: Respiratory and gastrointestinal symptoms followed by milk intake and persistent high milk-specific IgE titers were associated with persistent milk allergy.

Background: We have been conducting a two-day in-hospital parental education program -"Skin Care School"- on childhood atopic dermatitis since April 2007. The program comprises three lecture- and- practical session courses on skin care, the correct skin-cleaning procedure, and the application of ointments based on the "Finger Tip Unit." The program addresses caregivers of patients less than six years old suffering from moderate to severe atopic dermatitis., Methods: To evaluate the effectiveness of this program, questionnaires were administered to 56 participants before, immediately after, one month after, and six months after completion of the program., Results: Although the participants had received doctors' instructions on the amount of the ointments to be applied, most of them recognized on completing the program that they had been applying less amounts than prescribed. They added that the symptoms of the skin conditions, such as pruritus and sleeplessness, improved in one month after proper application and stabilized for six months. Moreover, the amounts of topical corticosteroid ointments required decreased following one month of treatment and reduced further in six months., Conclusion: This educational program was effective in imparting a sound understanding of skin care to the caregivers during their wards' short hospitalization. Appropriate skin care comprises cleaning the skin properly and applying adequate amounts of corticosteroid ointment and skin moisturizer, which results in improvements in conditions like eczema and a reduced requirement for corticosteroids.

Background: A kit, FASTKIT ELISA version II (Egg) (Nippon Meat Packers) is an enzyme-linked immunosorbent assay kit for detecting hen's egg proteins in foodstuffs. This kit is an enhanced version of FASTKIT ELISA (Egg) with a greater efficiency in terms of extraction of egg proteins from heated foodstuffs. However, the property of this kit remains to be fully elucidated., Methods: Using this new kit, we measured the amount of egg proteins in unheated or heated (140 degrees C or 180 degrees C, 20 min) homemade cookies containing whole egg, egg white or egg yolk., Results: The capability for detection of unheated or heated (140 degrees C or 180 degrees C) whole egg proteins was similar. In addition, there was no significant difference in the detectability between heated (140 degrees C) whole egg and egg white proteins. However, unheated or heated (140 degrees C or 180 degrees C) egg yolk proteins were not sufficiently measured by this kit., Conclusion: Our data suggest that this new kit is significantly improved for detection of heated egg white proteins as compared to that of old version, but not sufficient for detection of egg yolk proteins.

Background: A method for open food challenge test to determine food allergy has not been established in an evidence-based manner., Methods: We conducted an analysis of 438 open food challenges of raw milk (n=133, mean age 2.7+/-1.9 years), boiled egg white (n=216, 2.8+/-2.1 years) or udon noodles (n=89, 2.7+/-1.7 years) for the patients aged 1 year or more. Doses were increased (trace amounts, 1 g, 2 g, 5 g, 10 g, 20-30 g) every 20 minutes., Results: In total, 151 (38.5%) of food challenges were positive. The positive rates of milk, egg and wheat challenges were 35.8%, 42.4% and 33.3%, respectively. Of these, 76.2%, 32.5%, 27.8% and 0.7% had, respectively, skin, respiratory, gastrointestinal and cardiovascular symptoms. Although the prevalence of positive challenge increased with level of specific IgE, it did not correlate with the threshold amount of positive food challenge or the severity of symptoms. Among the challenge positive patients, 10.6% required injection of antihistamines, corticosteroids or adrenalines for the treatment of the symptoms., Conclusions: This challenge protocol seemed to be appropriate and safe.

Objective: We examined profiles and clinical symptoms of shrimp allergy patients and investigated the correlation of shrimp-specific IgE to crustaceans-specific IgE, mollusks-specific IgE and shellfish-specific IgE. In addition, symptoms when eating crustaceans other than shrimp, mollusks and shellfish were examined, because they shared tropomyosin as a major allergen., Methods: We examined 99 definitive shrimp allergy cases with questionnaire., Results: Their onset started during either childhood or young adulthood. Symptoms appeared within an hour after ingestion of shrimp in 87.9% cases. The most common symptoms were skin symptoms, followed by oral allergic syndrome (OAS) like symptoms, respiratory symptoms. Anaphylaxis were observed in 61 cases including 2 anaphylactic shock cases. Among 99 shrimp allergy cases, 44 cases (64.7%) showed positive reaction to crabs out of 68 cases experiencing crab ingestion. Only 11 cases (17.5%) reacted against squid out of 63 cases with the experience in squid ingestion. Crab-specific IgE (C.I. 0.954, p < 0.001) and squid-specific IgE (C.I. 0.582, p > 0.001) were strongly correlated with shrimp-specific IgE., Conclusion: We conclude that a lot of cases with shrimp allergy react to crabs clinically, and which seem to be different from the reaction against mollusk and shellfish intake in spite of sharing tropomyosin as a major allergen among them.

Eosinophilic inflammation of the airways is a key characteristic of asthma. Glucocorticoids can suppress the inflammatory response in part by promotion of eosinophilic apoptosis. We investigated the effects of glucocorticoids on leukocyte infiltration and apoptotic resolution of eosinophils and neutrophils in Sephadex-treated rat lung. Sephadex beads were injected intravenously, followed 24 h later by i.p. administration of dexamethasone (DEX, 0.1 mg/kg) or its vehicle. At 24 h post-DEX treatment, the bronchoalveolar lavage fluid (BALF) was collected. Differential leukocyte counts and the numbers of apoptotic eosinophils and neutrophils, and macrophages with engulfed eosinophils or neutrophils in BALF were determined microscopically from Diff-Quik stained cytospin preparations. Sephadex beads markedly increased cell counts of eosinophils and neutrophils in BALF. Compared with a vehicle-treated group, the DEX treatment significantly decreased the number of eosinophils, but not neutrophils, in BALF. Dexamethasone in BALF also significantly increased eosinophilic apoptosis and engulfment of apoptotic eosinophils by macrophages, but had no effect on neutrophilic apoptosis and engulfment of apoptotic neutrophils by macrophages. These results suggest that the increased clearance of eosinophils from airways by glucocorticoids may be partly due to the promotion of eosinophilic apoptosis.

Food allergy is frequently associated with atopic dermatitis (AD) in children. Appropriate elimination diet is necessary in the case of immediate food hypersensitivity, regardless it causes worsening of the chronic eczema or not. Here we report the prevalence of immediate type food allergy diagnosed by oral food challenge or the episodes of apparent acute allergic reaction in the AD patients (n=182, average age 4.9+/-5.1), who visited our clinic within one year. The prevalence of food allergy in the AD patients was 85.7% in age 0 years, 75.6% in age 1,65.4% in age 2, and declined to 13.9% in age 7 years old or more. The offending foods were egg, milk, wheat, fish and so on. The symptoms of food allergy included skin, gastrointestinal or respiratory manifestations, and also anaphylaxis. In conclusion, immediate type food allergy is frequently associated with childhood AD, and appropriate elimination of the offending food is necessary to avoid the acute allergic reaction including anaphylaxis.