今日の臨床サポート

食物アレルギー

著者: 柳田 紀之1) 相模原病院小児科

著者: 海老澤 元宏2) 相模原病院 臨床研究センターアレルギー性疾患研究部

監修: 上阪等 千葉西総合病院 膠原病リウマチセンター

著者校正/監修レビュー済:2022/07/06
参考ガイドライン:
  1. 日本小児アレルギー学会食物アレルギー委員会:食物アレルギー診療ガイドライン2021
  1. 食物アレルギーの診療の手引き2020
  1. 食物経口負荷試験の手引き2020
  1. 日本アレルギー学会:アナフィラキシーガイドライン
患者向け説明資料

概要・推奨   

早期対応
  1. 食物アレルギーが関与するアトピー性皮膚炎に関してはまず、アトピー性皮膚炎の早期治療が重要である(推奨度2)
  1. 食物アレルギーの発症予防のため、妊娠中や授乳中に母親が特定の食物を除去することは、効果がなく、母親の栄養状態に対して有害であり、推奨されない(推奨度1)
  1. どのようにして乳児早期に離乳食を摂取させるかなどの摂取方法や、食物アレルギーの発症頻度自体が少なかった乳、小麦、ゴマ、白身魚については更なる検討が必要であるが、鶏卵・ピーナッツに関しては早期摂取ができれば食物アレルギーの発症予防効果が期待できる(推奨度2)
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、 著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適応の査定において保険適応及び保険適応外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適応の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
柳田 紀之 : 特に申告事項無し[2022年]
海老澤 元宏 : 講演料(マイラン)[2022年]
監修:上阪等 : 特に申告事項無し[2022年]

改訂のポイント:
  1. 下記ガイドラインに基づき、記載内容を追記した。また、最新の文献を追加した。
  1. 日本小児アレルギー学会食物アレルギー委員会. 食物アレルギー診療ガイドライン2021
  1. 食物アレルギーの診療の手引き2020
  1. 食物経口負荷試験の手引き2020

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 食物アレルギーは「食物によって引き起こされる抗原特異的な免疫学的機序を介して生体にとって不利益な症状が惹起される現象」と定義される[1]
  1. アナフィラキシーとは、「アレルゲン等の侵入により、複数臓器に全身性にアレルギー症状が惹起され、生命に危機を与え得る過敏反応」と定義する。アナフィラキシーに血圧低下や意識障害を伴う場合を、アナフィラキシーショックという(別項参照)。
 
食物アレルギーの定義

食物アレルギーの定義:食物によって引き起こされる抗原特異的な免疫学的機序を介して生体にとって不利益な症状が惹起される現象

 
  1. 原因食物を摂取して2時間以内に症状が誘発される即時型、多くが即時型に移行する食物アレルギーの関与する乳児アトピー性皮膚炎型の2つが多い[2]。以降はこの2つの臨床型について解説する。
 
IgE依存性食物アレルギーの臨床型分類

a:定義:食物によって引き起こされる抗原特異的な免疫学的機序を介して生体にとって不利益な症状が惹起される現象
b:臨床型分類:小児の食物アレルギーは多くは食物アレルギーの関与する乳児アトピー性皮膚炎型として発症し、即時型に移行していく。
 
参考文献:食物アレルギー診療の手引き 2020

出典

img1:  食物アレルギーの診療の手引き2020
 
 
 
  1. わが国におけるIgE依存性食物アレルギー有症率は諸家の報告より、乳児が7.6-10%、2歳児が6.7%、3歳児が約5%、保育所児が4.0%、学童以降が1.3-4.5%とされている。全年齢を通して、わが国では推定1-2%程度の有症率であると考えられる[3]。男女比は2:1程度で男児が多い。
  1. 食物アレルギーの多くは自然寛解する。
問診・診察のポイント  
  1. 疑われる食物摂取後の症状と時間経過、アナフィラキシー歴の有無を確認する。

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文献 

Corinne A Keet, Robert A Wood, Elizabeth C Matsui
Limitations of reliance on specific IgE for epidemiologic surveillance of food allergy.
J Allergy Clin Immunol. 2012 Nov;130(5):1207-1209.e10. doi: 10.1016/j.jaci.2012.07.020. Epub 2012 Sep 7.
Abstract/Text
PMID 22964106
Noriyuki Yanagida, Takanori Minoura, Setsuko Kitaoka, Motohiro Ebisawa
A three-level stepwise oral food challenge for egg, milk, and wheat allergy.
J Allergy Clin Immunol Pract. 2017 Aug 25;. doi: 10.1016/j.jaip.2017.06.029. Epub 2017 Aug 25.
Abstract/Text
PMID 28847653
Robert A Wood, Scott H Sicherer, Brian P Vickery, Stacie M Jones, Andrew H Liu, David M Fleischer, Alice K Henning, Lloyd Mayer, A Wesley Burks, Alexander Grishin, Donald Stablein, Hugh A Sampson
The natural history of milk allergy in an observational cohort.
J Allergy Clin Immunol. 2013 Mar;131(3):805-12. doi: 10.1016/j.jaci.2012.10.060. Epub 2012 Dec 28.
Abstract/Text OBJECTIVE: There are few studies on the natural history of milk allergy. Most are single-site and not longitudinal, and these have not identified a means for early prediction of outcomes.
METHODS: Children aged 3 to 15 months were enrolled in an observational study with either (1) a convincing history of egg allergy, milk allergy, or both with a positive skin prick test (SPT) response to the trigger food and/or (2) moderate-to-severe atopic dermatitis (AD) and a positive SPT response to milk or egg. Children enrolled with a clinical history of milk allergy were followed longitudinally, and resolution was established by means of successful ingestion.
RESULTS: The cohort consists of 293 children, of whom 244 were given a diagnosis of milk allergy at baseline. Milk allergy has resolved in 154 (52.6%) subjects at a median age of 63 months and a median age at last follow-up of 66 months. Baseline characteristics that were most predictive of resolution included milk-specific IgE level, milk SPT wheal size, and AD severity (all P < .001). Baseline milk-specific IgG4 level and milk IgE/IgG4 ratio were not predictive of resolution and neither was expression of cytokine-inducible SH2-containing protein, forkhead box protein 3, GATA3, IL-10, IL-4, IFN-γ, or T-bet by using real-time PCR in CD25-selected, casein-stimulated mononuclear cells. A calculator to estimate resolution probabilities using baseline milk IgE level, SPT response, and AD severity was devised for use in the clinical setting.
CONCLUSIONS: In this cohort of infants with milk allergy, approximately one half had resolved over 66 months of follow-up. Baseline milk-specific IgE level, SPT wheal size, and AD severity were all important predictors of the likelihood of resolution.

Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
PMID 23273958
Jessica H Savage, Elizabeth C Matsui, Justin M Skripak, Robert A Wood
The natural history of egg allergy.
J Allergy Clin Immunol. 2007 Dec;120(6):1413-7. doi: 10.1016/j.jaci.2007.09.040.
Abstract/Text BACKGROUND: Egg allergy is very common, affecting 1% to 2% of children. It is generally thought that the majority of children with egg allergy develop tolerance in early childhood; however, this has not been examined in a large cohort with egg allergy.
OBJECTIVE: The purpose of the study was to estimate the proportion of children with egg allergy who develop egg tolerance and to identify predictors of tolerance development.
METHODS: Retrospective chart review of patients with egg allergy seen in a tertiary referral clinic. Patients were considered to have developed egg tolerance if they tolerated concentrated egg.
RESULTS: Kaplan-Meier analysis predicted resolution in 4% of patients with egg allergy by age 4 years, 12% by age 6 years, 37% by age 10 years, and 68% by age 16 years. Patients with persistent egg allergy had higher egg IgE levels at all ages to age 18 years. A patient's highest recorded egg IgE, presence of other atopic disease, and presence of other food allergy were significantly related to egg allergy persistence.
CONCLUSION: A majority of patients with egg allergy will develop egg tolerance, although the rate of tolerance development is slower than described previously. Egg IgE is predictive of allergy outcome and should be used in counseling patients on prognosis.
CLINICAL IMPLICATIONS: Most patients with egg allergy are likely to develop egg tolerance by late childhood, with the exception of patients with an egg IgE greater than 50 kU/L, who are unlikely to develop egg tolerance.

PMID 18073126
H S Skolnick, M K Conover-Walker, C B Koerner, H A Sampson, W Burks, R A Wood
The natural history of peanut allergy.
J Allergy Clin Immunol. 2001 Feb;107(2):367-74. doi: 10.1067/mai.2001.112129.
Abstract/Text BACKGROUND: It has traditionally been assumed that peanut allergy is rarely outgrown.
OBJECTIVE: The goal of this study was to determine the number of children with peanut allergy who become tolerant of peanut.
METHODS: Patients aged 4 to 20 years with a diagnosis of peanut allergy were evaluated by questionnaire, skin testing, and a quantitative antibody fluorescent-enzyme immunoassay. Patients who had been reaction free in the past year and had a peanut IgE (PN-IgE) level less than 20 kilounits of antibody per liter (kU(A)/L) were offered an open or double-blind, placebo-controlled peanut challenge.
RESULTS: A total of 223 patients were evaluated, and of those, 85 (PN-IgE < 0.35-20.4 kU(A)/L [median 1.42 kU(A)/L]) participated in an oral peanut challenge. Forty-eight (21.5%) patients had negative challenge results and were believed to have outgrown their peanut allergy (aged 4-17.5 years [median 6 years]; PN-IgE < 0.35-20.4 kU(A)/L [median 0.69 kU(A)/L]). Thirty-seven failed the challenge (aged 4-13 years [median 6.5 years]; RAST < 0.35-18.2 kU(A)/L [median 2.06 kU(A)/L]). Forty-one patients with PN-IgE levels less than 20 kU(A)/L declined to undergo challenge, and 97 were not eligible for challenge because their PN-IgE levels were greater than 20 kU(A)/L or they had had a recent reaction. Sixty-seven percent of patients with PN-IgE levels less than 2 kU(A)/L and 61% with levels less than 5 kU(A)/L had negative challenge results. Of those who underwent challenge, PN-IgE levels for those who passed versus those who failed were different at the time of challenge (P = .009), but not at the time of diagnosis (P = .25).
CONCLUSION: This study demonstrates that peanut allergy is outgrown in about 21.5% of patients. Patients with low PN-IgE levels should be offered a peanut challenge in a medical setting to demonstrate whether they can now tolerate peanuts.

PMID 11174206
Corinne A Keet, Elizabeth C Matsui, Gitika Dhillon, Patrick Lenehan, Melissa Paterakis, Robert A Wood
The natural history of wheat allergy.
Ann Allergy Asthma Immunol. 2009 May;102(5):410-5. doi: 10.1016/S1081-1206(10)60513-3.
Abstract/Text BACKGROUND: Wheat allergy is 1 of the most common food allergies in children, yet few data are available regarding its natural history.
OBJECTIVES: To define the natural course of wheat allergy and identify factors that help predict outcome in a large referral population of children with wheat allergy.
METHODS: Patients were included in the study if they had a history of a symptomatic reaction to wheat and a positive wheat IgE test result. Clinical history, laboratory results, and final outcome were recorded for 103 patients who met the inclusion criteria. Resolution of wheat allergy was determined based on food challenge results. Kaplan-Meier survival curves were generated to depict resolution of wheat allergy.
RESULTS: Rates of resolution were 29% by 4 years, 56% by 8 years, and 65% by 12 years. Higher wheat IgE levels were associated with poorer outcomes. The peak wheat IgE level recorded was a useful predictor of persistent allergy (P < .001), although many children outgrew wheat allergy with even the highest levels of wheat IgE.
CONCLUSION: The median age of resolution of wheat allergy is approximately 6 1/2 years in this population. In a significant minority of patients, wheat allergy persists into adolescence.

PMID 19492663
Justin M Skripak, Elizabeth C Matsui, Kim Mudd, Robert A Wood
The natural history of IgE-mediated cow's milk allergy.
J Allergy Clin Immunol. 2007 Nov;120(5):1172-7. doi: 10.1016/j.jaci.2007.08.023. Epub 2007 Nov 1.
Abstract/Text BACKGROUND: Cow's milk allergy (CMA) is the most common food allergy in infants and young children, affecting 2% to 3% of the general population. Most studies have shown the prognosis of developing tolerance to cow's milk to be good, with most outgrowing their allergy by age 3 years.
OBJECTIVE: To define the natural course of CMA and identify the factors that best predict outcome in a large referral population of children with CMA.
METHODS: Clinical history, test results, and final outcome were collected on 807 patients with IgE-mediated CMA. Patients were considered tolerant after they passed a challenge or experienced no reactions in the past 12 months and had a cow's milk IgE (cm-IgE) level <3 kU/L.
RESULTS: Rates of resolution were 19% by age 4 years, 42% by age 8 years, 64% by age 12 years, and 79% by 16 years. Patients with persistent allergy had higher cm-IgE levels at all ages to age 16 years. The highest cm-IgE for each patient, defined as peak cm-IgE, was found to be highly predictive of outcome (P < .001). Coexisting asthma (P < .001) and allergic rhinitis (P < .001) were also significant predictors of outcome.
CONCLUSION: The prognosis for CMA in this population is worse than previously reported. However, some patients developed tolerance during adolescence, indicating that follow-up and re-evaluation of CMA patients is important in their care. cm-IgE level is highly predictive of outcome.
CLINICAL IMPLICATIONS: The increasing potential for persistence of CMA, along with cm-IgE level's effect on prognosis, should be considered when counseling families regarding expected clinical course.

PMID 17935766
Arnon Elizur, Nelly Rajuan, Michael R Goldberg, Moshe Leshno, Adi Cohen, Yitzhak Katz
Natural course and risk factors for persistence of IgE-mediated cow's milk allergy.
J Pediatr. 2012 Sep;161(3):482-487.e1. doi: 10.1016/j.jpeds.2012.02.028. Epub 2012 Apr 4.
Abstract/Text OBJECTIVE: To describe the natural course of IgE-mediated cow's milk allergy (IgE-CMA) and to determine risk factors for its persistence in a population-based cohort.
STUDY DESIGN: In a prospective cohort study, 54 infants with IgE-CMA were identified from a population of 13 019 children followed from birth. Diagnosis of IgE-CMA was based on history, skin prick test (SPT), and an oral food challenge (OFC) when indicated. Allergic infants were followed for 48-60 months. Families were contacted by telephone every 6 months and asked about recent exposures to milk. OFC was repeated to evaluate for recovery. Clinical characteristics, SPT, and OFC outcomes were compared between infants with persistent IgE-CMA and infants who recovered.
RESULTS: Thirty-one infants (57.4%) recovered from IgE-CMA during the study period. Most infants (70.9%) recovered within the first 2 years. Risk factors for persistence on multivariate analysis included a reaction to <10 mL of milk on OFC (or on first exposure as estimated by the guardian, if OFC was not performed) (P = .01), a larger wheal size on SPT (P = .014), and age of ≤30 days at time of first reaction (P = .05).
CONCLUSIONS: Resolution occurs in most infants with IgE-CMA. Infants reacting to <10 mL of milk or in the first month of life, and those with a larger wheal size on SPT, are at increased risk for persistence.

Copyright © 2012 Mosby, Inc. All rights reserved.
PMID 22480700
Susanne Glaumann, Anna Nopp, S G O Johansson, Magnus P Borres, Caroline Nilsson
Oral peanut challenge identifies an allergy but the peanut allergen threshold sensitivity is not reproducible.
PLoS One. 2013;8(1):e53465. doi: 10.1371/journal.pone.0053465. Epub 2013 Jan 9.
Abstract/Text BACKGROUND: Double-blind placebo-controlled food challenge, DBPCFC, the gold standard for diagnosing food allergy, is time-consuming and potentially dangerous. A basophil allergen threshold sensitivity test, CD-sens, has shown promising results as a diagnostic tool in food allergy.
OBJECTIVES: To evaluate the reproducibility of oral peanut challenge and compare the outcome to CD-sens in peanut-sensitized children.
METHODS: Twenty-seven children (4-19 years) underwent a DBPCFC followed by a single-blind oral food-challenge. The peanut challenges (1 mg to 5 g) were evaluated by severity scoring. Blood samples were drawn for CD-sens before the two first challenges.
RESULTS: Thirteen children (48%) did not react at any of the challenges. Fourteen reacted at both peanut challenges but not to placebo. Only two of these children reacted at the same threshold dose and with the same severity score. All other children scored differently or reacted at different doses. For children with a positive challenge the geometric mean of the ratio of the doses was 1.834 (p = 0.307) and the arithmetic mean of the difference between the severity scores was 0.143 (p = 0.952). No association was obtained between the two peanut challenges regarding severity score (r(s) = 0.11, p = 0.71) or threshold dose (r(s) = 0.35, p = 0.22). Among the children positive in peanut challenge, 12 were positive in CD-sens. Two were low-responders and could not be evaluated. Geometric mean of the ratio of CD-sens values in children with a positive challenge was 1.035 (p = 0.505) but unlike for the severity score and the threshold dose the association between the two CD-sens values was strong (r(s) = 0.94, P<0.001).
CONCLUSIONS: For a positive/negative test the reproducibility is 100% for both peanut challenge and CD-sens. However, a comparison of the degree of allergen threshold sensitivity between the two tests is not possible since the threshold dose and severity scoring is not reproducible.

PMID 23326435
Aziz Sheikh, F Estelle R Simons, Victoria Barbour, Allison Worth
Adrenaline auto-injectors for the treatment of anaphylaxis with and without cardiovascular collapse in the community.
Cochrane Database Syst Rev. 2012 Aug 15;8:CD008935. doi: 10.1002/14651858.CD008935.pub2. Epub 2012 Aug 15.
Abstract/Text BACKGROUND: Anaphylaxis is a serious hypersensitivity reaction that is rapid in onset and may cause death. Adrenaline (epinephrine) auto-injectors are recommended as the initial, potentially life-saving treatment of choice for anaphylaxis in the community, but they are not universally available and have limitations in their use.
OBJECTIVES: To assess the effectiveness of adrenaline (epinephrine) auto-injectors in relieving respiratory, cardiovascular, and other symptoms during episodes of anaphylaxis that occur in the community.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 1), MEDLINE (Ovid SP) (1950 to January 2012), EMBASE (Ovid SP) (1980 to January 2012 ), CINAHL (EBSCO host) (1982 to January 2012 ), AMED (EBSCO host) (1985 to January 2012 ), LILACS, (BIREME) (1980 to January 2012 ), ISI Web of Science (1950 to January 2012 ). We adapted our search terms for other databases. We also searched websites listing on-going trials: the World Health Organization International Clinical Trials Registry Platform, the UK Clinical Research Network Study Portfolio, and the meta Register of Controlled Trials; and contacted pharmaceutical companies who manufacture adrenaline auto-injectors in an attempt to locate unpublished material.
SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing auto-injector administration of adrenaline with any control including no intervention, placebo, or other adrenergic agonists were eligible for inclusion.
DATA COLLECTION AND ANALYSIS: Two authors independently assessed articles for inclusion.
MAIN RESULTS: None of the 1328 studies that were identified satisfied the inclusion criteria.
AUTHORS' CONCLUSIONS: Based on this review, we cannot make any new recommendations on the effectiveness of adrenaline auto-injectors for the treatment of anaphylaxis. Although randomized, double-blind, placebo-controlled clinical trials of high methodological quality are necessary to define the true extent of benefits from the administration of adrenaline in anaphylaxis via an auto-injector, such trials are unlikely to be performed in individuals experiencing anaphylaxis because of ethical concerns associated with randomization to placebo. There is, however, a need to consider trials in which, for example, auto-injectors of different doses of adrenaline and differing devices are compared in order to provide greater clarity on the dose and device of choice. Such trials would be practically challenging to conduct. In the absence of appropriate trials, we recommend that adrenaline administration by auto-injector should still be regarded as the most effective first-line treatment for the management of anaphylaxis in the community. In countries where auto-injectors are not commonly used, it may be possible to conduct trials to compare administration of adrenaline via auto-injector with adrenaline administered by syringe and ampoule, or comparing the effectiveness of two different types of auto-injector.

PMID 22895980
A Sheikh, Y A Shehata, S G A Brown, F E R Simons
Adrenaline for the treatment of anaphylaxis: cochrane systematic review.
Allergy. 2009 Feb;64(2):204-12. doi: 10.1111/j.1398-9995.2008.01926.x.
Abstract/Text BACKGROUND: Anaphylaxis is a serious allergic reaction that is rapid in onset and may cause death. Adrenaline is recommended as the initial treatment of choice for anaphylaxis.
OBJECTIVES: To assess the benefits and harms of adrenaline in the treatment of anaphylaxis.
METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 1), MEDLINE (1966 to March 2007), EMBASE (1966 to March 2007), CINAHL (1982 to March 2007), BIOSIS (to March 2007), ISI Web of Knowledge (to March 2007) and LILACS (to March 2007). We also searched websites listing ongoing trials: http://www.clinicaltrials.gov/, http://www.controlledtrials.com and http://www.actr.org.au/ and contacted pharmaceutical companies and international experts in anaphylaxis in an attempt to locate unpublished material. Randomized and quasi-randomized controlled trials comparing adrenaline with no intervention, placebo or other adrenergic agonists were eligible for inclusion. Two authors independently assessed articles for inclusion.
RESULTS: We found no studies that satisfied the inclusion criteria.
CONCLUSIONS: On the basis of this review, we are unable to make any new recommendations on the use of adrenaline for the treatment of anaphylaxis. In the absence of appropriate trials, we recommend, albeit on the basis of less than optimal evidence, that adrenaline administration by intramuscular injection should still be regarded as first-line treatment for the management of anaphylaxis.

PMID 19178399
Sangeeta Dhami, Sukhmeet S Panesar, Tamara Rader, Antonella Muraro, Graham Roberts, Margitta Worm, Aziz Sheikh, EAACI Food Allergy and Anaphylaxis Guidelines group
The acute and long-term management of anaphylaxis: protocol for a systematic review.
Clin Transl Allergy. 2013 Apr 10;3(1):14. doi: 10.1186/2045-7022-3-14. Epub 2013 Apr 10.
Abstract/Text BACKGROUND: The European Academy of Allergy and Clinical Immunology is in the process of developing its Guideline for Food Allergy and Anaphylaxis, and this systematic review is one of seven inter-linked evidence syntheses that are being undertaken in order to provide a state-of-the-art synopsis of the current evidence base in relation to epidemiology, prevention, diagnosis and clinical management and impact on quality of life, which will be used to inform clinical recommendations.The aims of this systematic review will be to assess the effectiveness of interventions for the acute management of anaphylaxis, and pharmacological and non-pharmacological approaches for the long-term management of anaphylaxis.
METHODS: A highly sensitive search strategy has been developed, and validated study design filters will be applied to retrieve all articles pertaining to the management of anaphylaxis from electronic bibliographic databases. We will systematically review the literature on the acute management of anaphylaxis by assessing the effectiveness of epinephrine, H1-antihistamines (versus placebo), systemic glucocorticosteroids, methylxanthines or any other treatments for the emergency management of people experiencing anaphylaxis. The main interventions that have been studied in the context of long-term management are anaphylaxis management plans and allergen-specific immunotherapy.
DISCUSSION: There is at present little in the way of robust evidence to guide decisions on the acute and/or long-term management of anaphylaxis. Given the risk of death and the considerable morbidity associated with anaphylaxis these evidence gaps need to be filled wherever possible; this systematic review will make a start in this area.

PMID 23575342
A Sheikh, V Ten Broek, S G A Brown, F E R Simons
H1-antihistamines for the treatment of anaphylaxis: Cochrane systematic review.
Allergy. 2007 Aug;62(8):830-7. doi: 10.1111/j.1398-9995.2007.01435.x.
Abstract/Text BACKGROUND: Anaphylaxis is an acute systemic allergic reaction, which can be life-threatening. H(1)-antihistamines are commonly used as an adjuvant therapy in the treatment of anaphylaxis. We sought to assess the benefits and harm of H(1)-antihistamines in the treatment of anaphylaxis.
METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library); MEDLINE (1966 to June 2006); EMBASE (1966 to June 2006); CINAHL (1982 to June 2006) and ISI Web of Science (1945 to July 2006). We also contacted pharmaceutical companies and international experts in anaphylaxis in an attempt to locate unpublished material. Randomized and quasi-randomized-controlled trials comparing H(1)-antihistamines with placebo or no intervention were eligible for inclusion. Two authors independently assessed articles for inclusion.
RESULTS: We found no studies that satisfied the inclusion criteria.
CONCLUSIONS: Based on this review, we are unable to make any recommendations for clinical practice. Randomized-controlled trials are needed, although these are likely to prove challenging to design and execute.

PMID 17620060
K J L Choo, E Simons, Aziz Sheikh
Glucocorticoids for the treatment of anaphylaxis: Cochrane systematic review.
Allergy. 2010 Oct;65(10):1205-11. doi: 10.1111/j.1398-9995.2010.02424.x. Epub 2010 Jun 18.
Abstract/Text BACKGROUND: Anaphylaxis is a serious hypersensitivity reaction that is rapid in onset and may result in death. A number of guidelines recommend glucocorticoids for the treatment of people experiencing anaphylaxis.
OBJECTIVES: We sought to assess the benefits and harms of glucocorticoid treatment during episodes of anaphylaxis.
METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 3), MEDLINE (Ovid) (1966 to September 2009), EMBASE (Ovid) (1988 to September 2009), CINAHL (EBSCOhost) (to September 2009) and The Science Citation Index Expanded (SCI-EXPANDED) (1945 to September 2009). We also searched the UK National Research Register and websites listing ongoing trials and contacted international experts in anaphylaxis in an attempt to locate unpublished material. We sought to include randomized and quasi-randomized controlled trials comparing glucocorticoids with any control (either placebo, adrenaline (epinephrine), an antihistamine, or any combination of these). Two authors independently assessed articles for inclusion.
RESULTS: None of the 2496 reports identified satisfied the inclusion criteria.
CONCLUSIONS: We conclude that there is no evidence from high-quality studies for the use of steroids in the emergency management of anaphylaxis. Therefore, we can neither support nor refute the use of these drugs for this purpose.

PMID 20584003
Ananth Thyagarajan, Pooja Varshney, Stacie M Jones, Scott Sicherer, Robert Wood, Brian P Vickery, Hugh Sampson, A Wesley Burks
Peanut oral immunotherapy is not ready for clinical use.
J Allergy Clin Immunol. 2010 Jul;126(1):31-2. doi: 10.1016/j.jaci.2010.05.012.
Abstract/Text
PMID 20620564
Ulugbek Nurmatov, Iris Venderbosch, Graham Devereux, F Estelle R Simons, Aziz Sheikh
Allergen-specific oral immunotherapy for peanut allergy.
Cochrane Database Syst Rev. 2012 Sep 12;9:CD009014. doi: 10.1002/14651858.CD009014.pub2. Epub 2012 Sep 12.
Abstract/Text BACKGROUND: Peanut allergy is one of the most common forms of food allergy encountered in clinical practice.  In most cases, it does not spontaneously resolve; furthermore, it is frequently implicated in acute life-threatening reactions. The current management of peanut allergy centres on meticulous avoidance of peanuts and peanut-containing foods. Allergen-specific oral immunotherapy (OIT) for peanut allergy aims to induce desensitisation and then tolerance to peanut, and has the potential to revolutionise the management of peanut allergy. However, at present there is still considerable uncertainty about the effectiveness and safety of this approach.
OBJECTIVES: To establish the effectiveness and safety of OIT in people with IgE-mediated peanut allergy who develop symptoms after peanut ingestion.
SEARCH METHODS: We searched in the following databases: AMED, BIOSIS, CAB, CINAHL, The Cochrane Library, EMBASE, Global Health, Google Scholar, IndMed, ISI Web of Science, LILACS, MEDLINE, PakMediNet and TRIP. We also searched registers of on-going and unpublished trials. The date of the most recent search was January 2012.
SELECTION CRITERIA: Randomised controlled trials (RCTs), quasi-RCTs or controlled clinical trials involving children or adults with clinical features indicative of IgE-mediated peanut allergy treated with allergen-specific OIT, compared with control group receiving either placebo or no treatment, were eligible for inclusion.
DATA COLLECTION AND ANALYSIS: Two review authors independently checked and reviewed titles and abstracts of identified studies and assessed risk of bias. The full text of potentially relevant trials was assessed. Data extraction was independently performed by two reviewers with disagreements resolved through discussion.
MAIN RESULTS: We found one small RCT, judged to be at low risk of bias, that enrolled 28 children aged 1 to 16 years with evidence of sensitisation to peanut and a clinical history of reaction to peanut within 60 minutes of exposure. The study did not include children who had moderate to severe asthma or who had a history of severe peanut anaphylaxis. Randomisation was in a 2:1 ratio resulting in 19 children being randomised to the intervention arm and nine to the placebo arm. Intervention arm children received OIT with peanut flour and control arm participants received placebo comprising of oat flour. The primary outcome was assessed using a double-blind, placebo controlled oral food challenge (OFC) at approximately one year. No data were available on longer term outcomes beyond the OFC conducted at the end of the study.Because of adverse events, three patients withdrew from the intervention arm before the completion of the study. Therefore, only 16 participants received the full course of peanut OIT, whereas all nine patients receiving placebo completed the trial. The per-protocol analysis found a significant increase in the threshold dose of peanut allergen required to trigger a reaction in those in the intervention arm with all 16 participants able to ingest the maximum cumulative dose of 5000 mg of peanut protein (which the authors equate as being equivalent to approximately 20 peanuts) without developing symptoms, whereas in the placebo group they were able to ingest a median cumulative dose of 280 mg (range: 0 to 1900 mg, P < 0.001) before experiencing symptoms.  Per-protocol analyses also demonstrated that peanut OIT resulted in reductions in skin prick test size (P < 0.001), interleukin-5 (P = 0.01), interleukin-13 (P = 0.02) and an increase in peanut-specific immunoglobulin G(4) (IgG(4)) (P < 0.01).Children in the intervention arm experienced more adverse events during treatment than those in the placebo arm. In the initial day escalation phase, nine (47%) of the 19 participants initially enrolled in the OIT arm experienced clinically-relevant adverse events which required treatment with H(1)-antihistamines, two of which required additional treatment with epinephrine (adrenaline).
AUTHORS' CONCLUSIONS: The one small RCT we found showed that allergen-specific peanut OIT can result in desensitisation in children, and that this is associated with evidence of underlying immune-modulation. However, this treatment approach was associated with a substantial risk of adverse events, although the majority of these were mild.  In view of the risk of adverse events and the lack of evidence of long-term benefits, allergen-specific peanut OIT cannot currently be recommended as a treatment for the management of patients with IgE-mediated peanut allergy.  Larger RCTs are needed to investigate the acceptability, long-term effectiveness and cost-effectiveness of safer treatment regimens, particularly in relation to the induction of clinical and immunological tolerance.

PMID 22972130
Joanne P Yeung, Lorie A Kloda, Jason McDevitt, Moshe Ben-Shoshan, Reza Alizadehfar
Oral immunotherapy for milk allergy.
Cochrane Database Syst Rev. 2012 Nov 14;11:CD009542. doi: 10.1002/14651858.CD009542.pub2. Epub 2012 Nov 14.
Abstract/Text BACKGROUND: The mainstay of treatment of IgE-mediated cow milk allergy (IMCMA) is an avoidance diet, which is especially difficult with a ubiquitous food like milk. Milk oral immunotherapy (MOIT) may be an alternative treatment, through desensitization or induction of tolerance.
OBJECTIVES: We aim to assess the clinical efficacy and safety of MOIT in children and adults with IMCMA as compared to a placebo treatment or avoidance strategy.
SEARCH METHODS: We searched 13 databases for journal articles, conference proceedings, theses and unpublished trials, without language or date restrictions, using a combination of subject headings and text words. The search is up-to-date as of October 1, 2012.
SELECTION CRITERIA: Only randomised controlled trials (RCT) were considered for inclusion. Blinded and open trial designs were included. Children and adults with IMCMA were included. MOIT administered by any protocol were included.
DATA COLLECTION AND ANALYSIS: A total of 2111 unique records were identified and screened for potential inclusion. Studies were selected, data extracted and methodological quality assessed independently by two reviewers. We attempted to contact the study investigators to inquire about data not published that was required for the analysis. Statistical heterogeneity was assessed using the I² test. We estimated a pooled risk ratio (RR) for each outcome using a Mantel-Haenzel fixed-effect model if statistical heterogeneity was low as evaluated by an I² value less than 50%.
MAIN RESULTS: Of 157 records reviewed, 16 were included, representing five trials. In general, the studies were small and had inconsistent methodological rigor. Overall, the quality of evidence was rated as low. Each study used a different MOIT protocol. A total of 196 patients were studied (106 MOIT, 90 control) and all were children. Three studies were blinded and two used an avoidance diet control.  Sixty-six patients (62%) in the MOIT group were able to tolerate a full serving of milk (about 200 mL) compared to seven (8%) of the control group (RR 6.61, 95% CI 3.51 to 12.44). In addition, 27 (25%) in the MOIT group could ingest a partial serving of milk (10 to 184 mL) while none could in the control group (RR 9.34, 95% CI 2.72 to 32.09). None of the studies assessed the patients following a period off immunotherapy. Adverse reactions were common (97 of 106 MOIT patients had at least one symptom), although most were local and mild. Because of variability in reporting methods, adverse effects could not be combined quantitatively. For every 11 patients receiving MOIT, one required intramuscular epinephrine. One patient required it on two occasions.
AUTHORS' CONCLUSIONS: Studies to date have involved small numbers of patients and the quality of evidence is generally low. The current evidence shows that MOIT can lead to desensitization in the majority of individuals with IMCMA although the development of long-term tolerance has not been established. A major drawback of MOIT is the frequency of adverse effects, although most are mild and self-limited. The use of parenteral epinephrine is not infrequent. Because there are no standardized protocols, guidelines would be required prior to incorporating desensitization into clinical practice.

PMID 23152278
H A Sampson
Food allergy. Part 1: immunopathogenesis and clinical disorders.
J Allergy Clin Immunol. 1999 May;103(5 Pt 1):717-28.
Abstract/Text Up to 8% of children less than 3 years of age and approximately 2% of the adult population experience food-induced allergic disorders. A limited number of foods are responsible for the vast majority of food-induced allergic reactions: milk, egg, peanuts, fish, and tree nuts in children and peanuts, tree nuts, fish, and shellfish in adults. Food-induced allergic reactions are responsible for a variety of symptoms involving the skin, gastrointestinal tract, and respiratory tract and may be caused by IgE-mediated and non-IgE-mediated mechanisms. In part 1 of this series, immunopathogenic mechanisms and clinical disorders of food allergy are described.

PMID 10329801
Mitsuyoshi Urashima, Hidetoshi Mezawa, Mai Okuyama, Takashi Urashima, Daishi Hirano, Noriko Gocho, Hiroshi Tachimoto
Primary Prevention of Cow's Milk Sensitization and Food Allergy by Avoiding Supplementation With Cow's Milk Formula at Birth: A Randomized Clinical Trial.
JAMA Pediatr. 2019 Dec 1;173(12):1137-1145. doi: 10.1001/jamapediatrics.2019.3544.
Abstract/Text Importance: Cow's milk formula (CMF) is used to supplement breastfeeding (BF) at birth without clear clinical evidence to support the practice.
Objective: To determine whether avoiding supplementation with CMF at birth can decrease risks of sensitization to cow's milk protein and/or clinical food allergy, including cow's milk allergy (CMA), overall and in subgroups stratified by 25-hydroxyvitamin D (25[OH]D) levels.
Design, Setting, and Participants: The Atopy Induced by Breastfeeding or Cow's Milk Formula (ABC) trial, a randomized, nonblinded clinical trial, began enrollment October 1, 2013, and completed follow-up May 31, 2018, at a single university hospital in Japan. Participants included 330 newborns at risk for atopy; of these, 312 were included in the analysis. Data were analyzed from September 1 through October 31, 2018.
Interventions: Immediately after birth, newborns were randomized (1:1 ratio) to BF with or without amino acid-based elemental formula (EF) for at least the first 3 days of life (BF/EF group) or BF supplemented with CMF (≥5 mL/d) from the first day of life to 5 months of age (BF plus CMF group).
Main Outcomes and Measures: The primary outcome was sensitization to cow's milk (IgE level, ≥0.35 allergen units [UA]/mL) at the infant's second birthday. Secondary outcomes were immediate and anaphylactic types of food allergy, including CMA, diagnosed by oral food challenge test or triggered by food ingestion, with food-specific IgE levels of at least 0.35 UA/mL. Subgroup analysis was prespecified by tertiles of serum 25(OH)D levels at 5 months of age.
Results: Of the 312 infants included in the analysis (160 female [51.3%] and 152 male [48.7%]), 151 of 156 (96.8%) in the BF/EF and BF plus CMF groups were followed up until their second birthday. The primary outcome occurred in 24 infants (16.8%) in the BF/EF group, which was significantly fewer than the 46 infants (32.2%) in the BF plus CMF group (relative risk [RR], 0.52; 95% CI, 0.34-0.81). The middle tertile of the 25(OH)D subgroup, but not the low and high tertiles, had a significant interaction with the intervention (RR, 0.19; 95% CI, 0.07-0.50; P = .02). The prevalence of food allergy at the second birthday was significantly lower in the BF/EF than in the BF plus CMF groups for immediate (4 [2.6%] vs 20 [13.2%]; RR, 0.20; 95% CI, 0.07-0.57) and anaphylactic (1 [0.7%] vs 13 [8.6%]; RR, 0.08; 95% CI, 0.01-0.58) types.
Conclusions and Relevance: The evidence suggests that sensitization to cow's milk and food allergy, including CMA and anaphylaxis, are primarily preventable by avoiding CMF supplementation for at least the first 3 days of life.
Trial Registration: http://umin.ac.jp Identifier: UMIN000011577.

PMID 31633778
Tetsuhiro Sakihara, Kenta Otsuji, Yohei Arakaki, Kazuya Hamada, Shiro Sugiura, Komei Ito
Randomized trial of early infant formula introduction to prevent cow's milk allergy.
J Allergy Clin Immunol. 2021 Jan;147(1):224-232.e8. doi: 10.1016/j.jaci.2020.08.021. Epub 2020 Sep 2.
Abstract/Text BACKGROUND: Previous research has produced conflicting evidence on the preventive effects of early introduction of cow's milk protein on cow's milk allergy (CMA).
OBJECTIVE: Through a randomized controlled trial, we sought to determine whether the early introduction of cow's milk formula (CMF) could serve as an effective strategy in the primary prevention of CMA in a general population.
METHODS: We recruited newborns from 4 hospitals in Okinawa, Japan. Participants were randomly allocated to ingest at least10 mL of CMF daily (ingestion group) or avoid CMF (avoidance group) between 1 and 2 months of age. In the avoidance group breast-feeding was supplemented with soy formula as needed. Oral food challenge was performed at 6 months of age to assess CMA development. Continuous breast-feeding was recommended for both groups until 6 months of age.
RESULTS: We identified 504 infants for randomization into the 2 groups. In all, the parents of 12 participants declined to receive the intervention, and the study sample comprised 491 participants (242 in the ingestion group and 249 in the avoidance group) for a modified intention-to-treat analysis. There were 2 CMA cases (0.8%) among the 242 members of the ingestion group and 17 CMA cases (6.8%) among the 249 participants in the avoidance group (risk ratio = 0.12; 95% CI = 0.01-0.50; P < .001). The risk difference was 6.0% (95% CI = 2.7-9.3). Approximately 70% of the participants in both groups were still being breast-fed at 6 months of age.
CONCLUSIONS: Daily ingestion of CMF between 1 and 2 months of age prevents CMA development. This strategy does not compete with breast-feeding.

Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
PMID 32890574
Michael R Perkin, Kirsty Logan, Anna Tseng, Bunmi Raji, Salma Ayis, Janet Peacock, Helen Brough, Tom Marrs, Suzana Radulovic, Joanna Craven, Carsten Flohr, Gideon Lack, EAT Study Team
Randomized Trial of Introduction of Allergenic Foods in Breast-Fed Infants.
N Engl J Med. 2016 May 5;374(18):1733-43. doi: 10.1056/NEJMoa1514210. Epub 2016 Mar 4.
Abstract/Text BACKGROUND: The age at which allergenic foods should be introduced into the diet of breast-fed infants is uncertain. We evaluated whether the early introduction of allergenic foods in the diet of breast-fed infants would protect against the development of food allergy.
METHODS: We recruited, from the general population, 1303 exclusively breast-fed infants who were 3 months of age and randomly assigned them to the early introduction of six allergenic foods (peanut, cooked egg, cow's milk, sesame, whitefish, and wheat; early-introduction group) or to the current practice recommended in the United Kingdom of exclusive breast-feeding to approximately 6 months of age (standard-introduction group). The primary outcome was food allergy to one or more of the six foods between 1 year and 3 years of age.
RESULTS: In the intention-to-treat analysis, food allergy to one or more of the six intervention foods developed in 7.1% of the participants in the standard-introduction group (42 of 595 participants) and in 5.6% of those in the early-introduction group (32 of 567) (P=0.32). In the per-protocol analysis, the prevalence of any food allergy was significantly lower in the early-introduction group than in the standard-introduction group (2.4% vs. 7.3%, P=0.01), as was the prevalence of peanut allergy (0% vs. 2.5%, P=0.003) and egg allergy (1.4% vs. 5.5%, P=0.009); there were no significant effects with respect to milk, sesame, fish, or wheat. The consumption of 2 g per week of peanut or egg-white protein was associated with a significantly lower prevalence of these respective allergies than was less consumption. The early introduction of all six foods was not easily achieved but was safe.
CONCLUSIONS: The trial did not show the efficacy of early introduction of allergenic foods in an intention-to-treat analysis. Further analysis raised the question of whether the prevention of food allergy by means of early introduction of multiple allergenic foods was dose-dependent. (Funded by the Food Standards Agency and others; EAT Current Controlled Trials number, ISRCTN14254740.).

PMID 26943128
George Du Toit, Graham Roberts, Peter H Sayre, Henry T Bahnson, Suzana Radulovic, Alexandra F Santos, Helen A Brough, Deborah Phippard, Monica Basting, Mary Feeney, Victor Turcanu, Michelle L Sever, Margarita Gomez Lorenzo, Marshall Plaut, Gideon Lack, LEAP Study Team
Randomized trial of peanut consumption in infants at risk for peanut allergy.
N Engl J Med. 2015 Feb 26;372(9):803-13. doi: 10.1056/NEJMoa1414850. Epub 2015 Feb 23.
Abstract/Text BACKGROUND: The prevalence of peanut allergy among children in Western countries has doubled in the past 10 years, and peanut allergy is becoming apparent in Africa and Asia. We evaluated strategies of peanut consumption and avoidance to determine which strategy is most effective in preventing the development of peanut allergy in infants at high risk for the allergy.
METHODS: We randomly assigned 640 infants with severe eczema, egg allergy, or both to consume or avoid peanuts until 60 months of age. Participants, who were at least 4 months but younger than 11 months of age at randomization, were assigned to separate study cohorts on the basis of preexisting sensitivity to peanut extract, which was determined with the use of a skin-prick test--one consisting of participants with no measurable wheal after testing and the other consisting of those with a wheal measuring 1 to 4 mm in diameter. The primary outcome, which was assessed independently in each cohort, was the proportion of participants with peanut allergy at 60 months of age.
RESULTS: Among the 530 infants in the intention-to-treat population who initially had negative results on the skin-prick test, the prevalence of peanut allergy at 60 months of age was 13.7% in the avoidance group and 1.9% in the consumption group (P<0.001). Among the 98 participants in the intention-to-treat population who initially had positive test results, the prevalence of peanut allergy was 35.3% in the avoidance group and 10.6% in the consumption group (P=0.004). There was no significant between-group difference in the incidence of serious adverse events. Increases in levels of peanut-specific IgG4 antibody occurred predominantly in the consumption group; a greater percentage of participants in the avoidance group had elevated titers of peanut-specific IgE antibody. A larger wheal on the skin-prick test and a lower ratio of peanut-specific IgG4:IgE were associated with peanut allergy.
CONCLUSIONS: The early introduction of peanuts significantly decreased the frequency of the development of peanut allergy among children at high risk for this allergy and modulated immune responses to peanuts. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT00329784.).

PMID 25705822
George Du Toit, Peter H Sayre, Graham Roberts, Michelle L Sever, Kaitie Lawson, Henry T Bahnson, Helen A Brough, Alexandra F Santos, Kristina M Harris, Suzana Radulovic, Monica Basting, Victor Turcanu, Marshall Plaut, Gideon Lack, Immune Tolerance Network LEAP-On Study Team
Effect of Avoidance on Peanut Allergy after Early Peanut Consumption.
N Engl J Med. 2016 Apr 14;374(15):1435-43. doi: 10.1056/NEJMoa1514209. Epub 2016 Mar 4.
Abstract/Text BACKGROUND: In a randomized trial, the early introduction of peanuts in infants at high risk for allergy was shown to prevent peanut allergy. In this follow-up study, we investigated whether the rate of peanut allergy remained low after 12 months of peanut avoidance among participants who had consumed peanuts during the primary trial (peanut-consumption group), as compared with those who had avoided peanuts (peanut-avoidance group).
METHODS: At the end of the primary trial, we instructed all the participants to avoid peanuts for 12 months. The primary outcome was the percentage of participants with peanut allergy at the end of the 12-month period, when the participants were 72 months of age.
RESULTS: We enrolled 556 of 628 eligible participants (88.5%) from the primary trial; 550 participants (98.9%) had complete primary-outcome data. The rate of adherence to avoidance in the follow-up study was high (90.4% in the peanut-avoidance group and 69.3% in the peanut-consumption group). Peanut allergy at 72 months was significantly more prevalent among participants in the peanut-avoidance group than among those in the peanut-consumption group (18.6% [52 of 280 participants] vs. 4.8% [13 of 270], P<0.001). Three new cases of allergy developed in each group, but after 12 months of avoidance there was no significant increase in the prevalence of allergy among participants in the consumption group (3.6% [10 of 274 participants] at 60 months and 4.8% [13 of 270] at 72 months, P=0.25). Fewer participants in the peanut-consumption group than in the peanut-avoidance group had high levels of Ara h2 (a component of peanut protein)-specific IgE and peanut-specific IgE; in addition, participants in the peanut-consumption group continued to have a higher level of peanut-specific IgG4 and a higher peanut-specific IgG4:IgE ratio.
CONCLUSIONS: Among children at high risk for allergy in whom peanuts had been introduced in the first year of life and continued until 5 years of age, a 12-month period of peanut avoidance was not associated with an increase in the prevalence of peanut allergy. Longer-term effects are not known. (Funded by the National Institute of Allergy and Infectious Diseases and others; LEAP-On ClinicalTrials.gov number, NCT01366846.).

PMID 26942922
Osamu Natsume, Shigenori Kabashima, Junko Nakazato, Kiwako Yamamoto-Hanada, Masami Narita, Mai Kondo, Mayako Saito, Ai Kishino, Tetsuya Takimoto, Eisuke Inoue, Julian Tang, Hiroshi Kido, Gary W K Wong, Kenji Matsumoto, Hirohisa Saito, Yukihiro Ohya, PETIT Study Team
Two-step egg introduction for prevention of egg allergy in high-risk infants with eczema (PETIT): a randomised, double-blind, placebo-controlled trial.
Lancet. 2017 Jan 21;389(10066):276-286. doi: 10.1016/S0140-6736(16)31418-0. Epub 2016 Dec 9.
Abstract/Text BACKGROUND: Evidence is accumulating that early consumption is more beneficial than is delayed introduction as a strategy for primary prevention of food allergy. However, allergic reactions caused by early introduction of such solid foods have been a problematic issue. We investigated whether or not early stepwise introduction of eggs to infants with eczema combined with optimal eczema treatment would prevent egg allergy at 1 year of age.
METHODS: In this randomised, double-blind, placebo-controlled trial, we enrolled infants 4-5 months of age with eczema from two centres in Japan. Exclusion criteria were being born before 37 weeks of gestational age, experience of ingestion of hen's eggs or egg products, history of immediate allergic reaction to hen's eggs, history of non-immediate allergic reaction to a particular type of food, and complications of any severe disease. Infants were randomly assigned (block size of four; stratified by institution and sex) to early introduction of egg or placebo (1:1). Participants in the egg group consumed orally 50 mg of heated egg powder per day from 6 months to 9 months of age and 250 mg per day thereafter until 12 months of age. We aggressively treated participants' eczema at entry and maintained control without exacerbations throughout the intervention period. Participants and physicians were masked to assignment, and allocation was concealed. The primary outcome was the proportion of participants with hen's egg allergy confirmed by open oral food challenges at 12 months of age, assessed blindly by standardised methods, in all randomly allocated participants who received the intervention. This trial is registered with the University Hospital Medical Information Network Clinical Trials Registry, number UMIN000008673.
FINDINGS: Between Sept 18, 2012, and Feb 13, 2015, we randomly allocated 147 participants (73 [50%] to the egg group and 74 [50%] to the placebo group). This trial was terminated on the basis of the results of the scheduled interim analysis of 100 participants, which showed a significant difference between the two groups (four [9%] of 47 participants had an egg allergy in the egg group vs 18 [38%] of 47 in the placebo group; risk ratio 0·222 [95% CI 0·081-0·607]; p=0·0012). In the primary analysis population, five (8%) of 60 participants had an egg allergy in the egg group compared with 23 (38%) of 61 in the placebo group (risk ratio 0·221 [0·090-0·543]; p=0·0001). The only difference in adverse events between groups was admissions to hospital (six [10%] of 60 in the egg group vs none in the placebo group; p=0·022). 19 acute events occurred in nine (15%) participants in the egg group versus 14 events in 11 (18%) participants in the placebo group after intake of the trial powder.
INTERPRETATION: Introduction of heated egg in a stepwise manner along with aggressive eczema treatment is a safe and efficacious way to prevent hen's egg allergy in high-risk infants. In this study, we developed a practical approach to overcome the second wave of the allergic epidemic caused by food allergy.
FUNDING: Ministry of Health, Labour and Welfare, and National Centre for Child Health and Development, Japan.

Copyright © 2017 Elsevier Ltd. All rights reserved.
PMID 27939035
Kunie Kohno, Hiroaki Matsuo, Hitoshi Takahashi, Hiroyuki Niihara, Yuko Chinuki, Sakae Kaneko, Tsutomu Honjoh, Tatsuya Horikawa, Shoji Mihara, Eishin Morita
Serum gliadin monitoring extracts patients with false negative results in challenge tests for the diagnosis of wheat-dependent exercise-induced anaphylaxis.
Allergol Int. 2013 Jun;62(2):229-38. doi: 10.2332/allergolint.12-OA-0495. Epub 2013 Apr 25.
Abstract/Text BACKGROUND: Challenge testing with wheat plus exercise and/or aspirin is a gold standard for the diagnosis of wheat-dependent exercise-induced anaphylaxis (WDEIA); however, the test may often yield false-negative results. Our previous study suggested that an increase in serum wheat gliadin levels is required to induce allergic symptoms in patients with WDEIA. Based on this knowledge, we sought to extract the patients with false negative results in the challenge tests of WDEIA.
METHODS: Thirty-six patients with suspected WDEIA were enrolled. First, group categorizations-Group I, challenge tests were positive; Group II, challenge tests were negative and serum gliadin were undetectable; Group III, challenge tests were negative and serum gliadin were detectable-were given according to the results of wheat plus exercise and/or aspirin challenge testing and serum gliadin levels. Second, diagnoses were made using retests and/or dietary management in Group II and III.
RESULTS: Positive results for wheat plus exercise and/or aspirin challenge tests gave a diagnosis of definite WDEIA in 17 of 36 patients (Group I). Of the remaining 19 challenge negative patients, serum gliadin was undetectable in ten patients (Group II). Of the ten patients (Group II), three of them were diagnosed as definite WDEIA by retesting and six of them were diagnosed as probable WDEIA using a wheat elimination diet, whereas one patient was non-WDEIA. In the rest of the nine challenge negative patients, serum gliadin was detectable (Group III). No allergic episodes with a normal diet provided a diagnosis of non-WDEIA in seven of the nine patients, whereas the remaining two patients were probable WDEIA or had another food allergy because of repeated episodes.
CONCLUSIONS: Our study revealed that serum gliadin monitoring during challenge testing is useful.

PMID 23612492

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