We proposed two types of allergic response: IgE-dependent and IgE-independent, and designate these as 'acquired-type allergy' and 'innate-type allergy', respectively. IL-18 and IL-33 are essential regulators for 'innate-type allergy'. Especially, IL-33 stimulates both innate (basophils, mast cells, or group 2 innate lymphoid cells) and acquired (Th2 cells) allergy-related cells to induce and/or augment Th2 cytokine production, which leads to eosinophilic inflammation in vivo. Thus, IL-33 is an essential regulator for both 'innate-type allergy' and 'acquired-type allergy', and might be a therapeutic target for allergic diseases.

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Number of clinical reports about non-IgE-mediated gastrointestinal food allergies is abruptly increasing in Japan since the late 1990's. However, unlike the case of IgE-mediated food allergy, development of diagnostic laboratory tests and our understanding of the immunological mechanisms involved in non-IgE-mediated gastrointestinal food allergies lag. Although the clinical entities in Western countries have been well established, the clinical phenotypes are somewhat different in Japanese patients when compared with these of Western countries, and clinicians have sometimes experienced confusion. Aiming at solving this problem, we performed clinical research and determined a useful method for dividing patients into four clusters with distinctive clinical symptoms. In this review paper, we will explain about tips for diagnosis and treatment procedure of these four subgroups.

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Intramuscular adrenalin injection is the first line treatment for anaphylactic shock, and an adrenalin auto-injector (Epipen^®) is commercially available in Japan. A total of 211 prescriptions were given to 117 patients from August 2005 to February 2011. The patients' age at thetime of their first prescription ranged from 2.5 to 27.8 years (median: 7.0 years). The dominant offending allergens were hen's eggs (n=56) and cow's milk (n=55). Six patients (5.1%) used the injector, four of them used it as a pre-hospital care and the others used it in the hospital. One accidental shot was reported when the injector was dropped on the floor at school. A questionnaire to the parents and the patients, who were 12 years of age or more, revealed that almost half of the patients and parents did not feel confident in their judgment of when to use Epipen^®. Few patients repeatedly practiced the use of this injector at home, and nearly half of all parents did not understand whether or not there was an emergency plan including the administration of Epipen^® in schools. In conclusion, precise instructions at the time of prescription, and repeated education should be emphasized for all patients that had a prescription of an Epipen^®.

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【Background】 We evaluated diet instructions developed for patients with egg allergies aiming to achieve release from elimination by eating as much eggs as possible. The patients began to consume egg whites quantitatively based on the results of an oral food challenge test. In the present paper, we examined the level of consumption after one year of follow-up after providing diet instructions to increase the dose of eggs.
【Methods】 The subjects included 40 patients (median age: 35.5 months) with positive egg challenge test results who started consuming 2 g or more of boiled egg whites according to the policy reported in our previous paper. If the patients were able to consume the instructed amount five to ten times safely, they were allowed to increase the doseabout 1.2 times. After one year of repeated diet instructions, we evaluated the level of egg consumption. With respect to a control group, we conducted a retrospective chart review of 40 patients who exhibited positive egg challenge test results before we initiated the study of the quantitative diet instructions.
【Results】 After one year of diet instructions, 63% of the subjects were able to consume more than half of one egg. This percentage was significantly higher than that observed in the control group (15%, p<0.01). On the other hand, the number of patients who consumed less than 1/20 eggs after one year was only one (3%) in the subject group and 22 (55%) in the control group.
【Conclusions】 The diet instructions to 'eat as much as possible' were shown to be effective inincreasing the level of consumptionearlier in patients with egg allergies.

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Purpose: We evaluated the efficacy of the original diet instructions that had been developed to enable patients to avoid milk elimination by monitoring the amount of safe milk ingestion.
Methods: Thirty-one children (median age: 45.0 months) with positive milk challenge tests were recruited in this study. Based on the threshold dose and the severity of symptoms observed during the challenge test, all of them fulfilled the criteria for initiating consumption of 2 ml or more of milk. We evaluated the patients' diet diary in the follow-up visit, and when they were able to consume the instructed dose five to 10 times without experiencing any adverse symptoms, then we allowed them to increase the dose by 10% to 20%. After one year, the tolerated dose of milk was evaluated. As a control group, a retrospective chart review was performed for the 31 patients who underwent milk challenges before the present study and fulfilled the comparative criteria of the challenge results.
Results: The subjects were able to increase the dose of milk without experiencing any serious symptoms at home. After one year, 11 children (35.5%) were consuming 50 ml or more of milk. Only one patient remained who consumed less than 5 ml of milk; this number was significantly less than that observed in the control group (eight patients, p<0.05).
Conclusion: The quantitative diet instructions were found to be safe and effective for enabling patients to avoid complete elimination and thereby gradually increase their milk intake.

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Purpose: The purpose of this study was to evaluate quantitative diet instructions developed to release patients with wheat allergies from food elimination.
Methods: We recruited 35 children (median age: 24 months) with positive wheat challenge test results obtained using udon noodles who met the criteria to initiate the ingestion of 2 g or more of udon noodles based on the threshold level and severity of symptoms. Oral wheat challenge tests were carried out at our institute between September 2010 and July 2011. The diet instructions consisted of quantitative intake of udon noodles or pasta. When safety was confirmed, the amount was increased 10% to 20%. The patients were allowed to consume other wheat products and recipes by converting the content of wheat protein. The amount of wheat ingestion attained after one year was evaluated and compared with that observed in 37 control patients before the implementation of the diet instructions.
Results: According to questionnaires completed by the subjects' parents after six months, the allergic symptoms accompanying the wheat intake were mild, such as discomfort in the mouth or redness around the mouth. The median amount of udon ingestion attained after one year was 80 g, which was significantly more than that observed in the control group (30 g). However, some patients continued to exclusively eat udon noodles or a few pieces of wheat snacks.
Conclusion: The diet instructions were shown to be efficient and safe for releasing patients from wheat elimination. However, some patients required more detailed diet instructions regarding the introduction of allergic foods into their daily meals.

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Purpose: The diagnosis of food allergy has been gradually standardized with the spread of manuals and guidelines. However, there are still some occasions, where instructions of inappropriate food elimination lead to low patients' height. We clarified how the inappropriate instructions affect patients' height.
Methods: We examined 34 patients who had eliminated a lot of foods by a pediatric outpatient clinic department prior to the visit to our department (inappropriate group), and 119 patients with the standard diagnosis and the nutritious guidance based on minimal food elimination (standard group). The height standard deviation scores (HtSDS) of each subject were calculated.
Results: In inappropriate group the number of eliminated foods has been declined tremendously from 6.5 items to 3.0 items before and after first oral food challenge test. In standard group the number of eliminated foods has been declined from 4.0 items to 3.1 items. The inappropriate group have significantly lower HtSDS than the standard group.
Discussion: By the food elimination based on appropriate diagnoses based on food challenge test, the number of eliminated foods has been declined remarkably. We hope that food allergy patients get the standard diagnosis and the nutritious guidance based on minimal food elimination, even though they have to eliminate causative foods to avoid adverse reactions.

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[in Japanese]

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