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1.  Early Life Eczema, Food Introduction, and Risk of Food Allergy in Children 
The effect of food introduction timing on the development of food allergy remains controversial. We sought to examine whether the presence of childhood eczema changes the relationship between timing of food introduction and food allergy. The analysis includes 960 children recruited as part of a family-based food allergy cohort. Food allergy was determined by objective symptoms developing within 2 hours of ingestion, corroborated by skin prick testing/specific IgE. Physician diagnosis of eczema and timing of formula and solid food introduction were obtained by standardized interview. Cox Regression analysis provided hazard ratios for the development of food allergy for the same subgroups. Logistic regression models estimated the association of eczema and formula/food introduction with the risk of food allergy, individually and jointly. Of the 960 children, 411 (42.8%) were allergic to 1 or more foods and 391 (40.7%) had eczema. Children with eczema had a 8.4-fold higher risk of food allergy (OR, 95% CI: 8.4, 5.9–12.1). Among all children, later (>6 months) formula and rice/wheat cereal introduction lowered the risk of food allergy. In joint analysis, children without eczema who had later formula (OR, 95% CI: 0.5, 0.3–0.9) and later (>1 year) solid food (OR, 95% CI: 0.5, 0.3–0.95) introduction had a lower risk of food allergy. Among children with eczema, timing of food or formula introduction did not modify the risk of developing food allergy. Later food introduction was protective for food allergy in children without eczema but did not alter the risk of developing food allergy in children with eczema.
doi:10.1089/ped.2010.0014
PMCID: PMC3281290  PMID: 22375277
2.  The impact of food allergy on asthma 
Food allergy is a potentially severe immune response to a food or food additive. Although a majority of children will outgrow their food allergies, some may have lifelong issues. Food allergies and other atopic conditions, such as asthma, are increasing in prevalence in Western countries. As such, it is not uncommon to note the co-existence of food allergy and asthma in the same patient. As part of the atopic march, many food allergic patients may develop asthma later in life. Each can adversely affect the other. Food allergic patients with asthma have a higher risk of developing life-threatening food-induced reactions. Although food allergy is not typically an etiology of asthma, an asthmatic patient with food allergy may have higher rates of morbidity and mortality associated with the asthma. Asthma is rarely a manifestation of food allergy alone, but the symptoms can be seen with allergic reactions to foods. There may be evidence to suggest that early childhood environmental factors, such as the mother’s and child’s diets, factor in the development of asthma; however, the evidence continues to be conflicting. All food allergic patients and their families should be counseled on the management of food allergy and the risk of developing co-morbid asthma.
PMCID: PMC3047906  PMID: 21437041
food allergy; diagnosis; treatment; asthma
3.  Food allergy: an overview. 
Environmental Health Perspectives  2003;111(2):223-225.
Food allergy affects between 5% and 7.5% of children and between 1% and 2% of adults. The greater prevalence of food allergy in children reflects both the increased predisposition of children to develop food allergies and the development of immunologic tolerance to certain foods over time. Immunoglobulin (Ig) E-mediated food allergies can be classified as those that persist indefinitely and those that are predominantly transient. Although there is overlap between the two groups, certain foods are more likely than others to be tolerated in late childhood and adulthood. The diagnosis of food allergy rests with the detection of food-specific IgE in the context of a convincing history of type I hypersensitivity-mediated symptoms after ingestion of the suspected food or by eliciting IgE-mediated symptoms after controlled administration of the suspected food. Presently, the only available treatment of food allergies is dietary vigilance and administration of self-injectable epinephrine.
PMCID: PMC1241355  PMID: 12573910
4.  Food allergy knowledge, attitudes and beliefs: Focus groups of parents, physicians and the general public 
BMC Pediatrics  2008;8:36.
Background
Food allergy prevalence is increasing in US children. Presently, the primary means of preventing potentially fatal reactions are avoidance of allergens, prompt recognition of food allergy reactions, and knowledge about food allergy reaction treatments. Focus groups were held as a preliminary step in the development of validated survey instruments to assess food allergy knowledge, attitudes, and beliefs of parents, physicians, and the general public.
Methods
Eight focus groups were conducted between January and July of 2006 in the Chicago area with parents of children with food allergy (3 groups), physicians (3 groups), and the general public (2 groups). A constant comparative method was used to identify the emerging themes which were then grouped into key domains of food allergy knowledge, attitudes, and beliefs.
Results
Parents of children with food allergy had solid fundamental knowledge but had concerns about primary care physicians' knowledge of food allergy, diagnostic approaches, and treatment practices. The considerable impact of children's food allergies on familial quality of life was articulated. Physicians had good basic knowledge of food allergy but differed in their approach to diagnosis and advice about starting solids and breastfeeding. The general public had wide variation in knowledge about food allergy with many misconceptions of key concepts related to prevalence, definition, and triggers of food allergy.
Conclusion
Appreciable food allergy knowledge gaps exist, especially among physicians and the general public. The quality of life for children with food allergy and their families is significantly affected.
doi:10.1186/1471-2431-8-36
PMCID: PMC2564918  PMID: 18803842
5.  Season of Birth is Associated with Food Allergy in Children 
Background
The prevalence of food allergy is rising and etiologic factors remain uncertain. Evidence implicates a role of vitamin D in the development of atopic diseases. Based on seasonal patterns of UVB exposure (and consequent vitamin D status), we hypothesized that food allergy patients are more often born in fall or winter.
Objective
Investigate whether season of birth is associated with food allergy.
Methods
We performed a multicenter chart review of all patients presenting to three Boston emergency departments (EDs) for food-related acute allergic reactions between 1/1/01 and 12/31/06. Months of birth among food allergy patients were compared to those of patients visiting the ED for reasons other than food allergy.
Results
We studied 1,002 food allergy patients. Among younger children with food allergy (age <5 years) – but not among older children or adults – 41% were born in spring/summer compared to 59% in fall/winter (P=0.002). This approximately 40/60 ratio differed from birth season of children treated in the ED for non-food allergy reasons (P=0.002). Children <5 years old born in fall/winter had a 53% higher odds of food allergy compared to controls. This finding was independent of the suspected triggering food and allergic comorbidities.
Conclusions
Food allergy is more common in Boston children who were born in the fall and winter seasons. We propose that these findings are mediated by seasonal differences in UVB exposure. These results add support to the hypothesis that seasonal fluctuations in sunlight and perhaps vitamin D may be involved in the pathogenesis of food allergy.
doi:10.1016/j.anai.2010.01.019
PMCID: PMC2941399  PMID: 20408340
Food allergy; season of birth; epidemiology; UVB; vitamin D
6.  Diagnosis and management of non-IgE-mediated cow’s milk allergy in infancy - a UK primary care practical guide 
The UK NICE guideline on the Diagnosis and Assessment of Food Allergy in Children and Young People was published in 2011, highlighting the important role of primary care physicians, dietitians, nurses and other community based health care professionals in the diagnosis and assessment of IgE and non-IgE-mediated food allergies in children. The guideline suggests that those with suspected IgE-mediated disease and those suspected to suffer from severe non-IgE-mediated disease are referred on to secondary or tertiary level care. What is evident from this guideline is that the responsibility for the diagnostic food challenge, ongoing management and determining of tolerance to cow’s milk in children with less severe non-IgE-mediated food allergies is ultimately that of the primary care/community based health care staff, but this discussion fell outside of the current NICE guideline. Some clinical members of the guideline development group (CV, JW, ATF, TB) therefore felt that there was a particular need to extend this into a more practical guideline for cow’s milk allergy. This subset of the guideline development group with the additional expertise of a paediatric gastroenterologist (NS) therefore aimed to produce a UK Primary Care Guideline for the initial clinical recognition of all forms of cow’s milk allergy and the ongoing management of those with non-severe non-IgE-mediated cow’s milk allergy in the form of algorithms. These algorithms will be discussed in this review paper, drawing on guidance primarily from the UK NICE guideline, but also from the DRACMA guidelines, ESPGHAN guidelines, Australian guidelines and the US NIAID guidelines.
doi:10.1186/2045-7022-3-23
PMCID: PMC3716921  PMID: 23835522
Cow’s milk allergy; Primary care; Food allergy; Diagnosis; Management; Hypoallergenic formula
7.  Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy 
Background
IgE-mediated peanut allergy is a complex trait with strong heritability, but its genetic basis is currently unknown. Loss-of-function mutations within the filaggrin gene are associated with atopic dermatitis and other atopic diseases; therefore, filaggrin is a candidate gene in the etiology of peanut allergy.
Objective
To investigate the association between filaggrin loss-of-function mutations and peanut allergy.
Methods
Case-control study of 71 English, Dutch, and Irish oral food challenge–positive patients with peanut allergy and 1000 non peanut-sensitized English population controls. Replication was tested in 390 white Canadian patients with peanut allergy (defined by food challenge, or clinical history and skin prick test wheal to peanut ≥8 mm and/or peanut-specific IgE ≥15 kUL−1) and 891 white Canadian population controls. The most prevalent filaggrin loss-of-function mutations were assayed in each population: R501X and 2282del4 in the Europeans, and R501X, 2282del4, R2447X, and S3247X in the Canadians. The Fisher exact test and logistic regression were used to test for association; covariate analysis controlled for coexistent atopic dermatitis.
Results
Filaggrin loss-of-function mutations showed a strong and significant association with peanut allergy in the food challenge–positive patients (P = 3.0 × 10−6; odds ratio, 5.3; 95% CI, 2.8-10.2), and this association was replicated in the Canadian study (P = 5.4 × 10−5; odds ratio, 1.9; 95% CI, 1.4-2.6). The association of filaggrin mutations with peanut allergy remains significant (P = .0008) after controlling for coexistent atopic dermatitis.
Conclusion
Filaggrin mutations represent a significant risk factor for IgE-mediated peanut allergy, indicating a role for epithelial barrier dysfunction in the pathogenesis of this disease.
doi:10.1016/j.jaci.2011.01.031
PMCID: PMC3081065  PMID: 21377035
Atopic dermatitis; filaggrin; IgE; peanut allergy; risk factor; AD, Atopic dermatitis; ALSPAC, Avon Longitudinal Study of Parents and Children; FLG, Filaggrin; OR, Odds ratio; SPT, Skin prick test; UK, United Kingdom
8.  Heated Allergens and Induction of Tolerance in Food Allergic Children 
Nutrients  2013;5(6):2028-2046.
Food allergies are one of the first manifestations of allergic disease and have been shown to significantly impact on general health perception, parental emotional distress and family activities. It is estimated that in the Western world, almost one in ten children have an IgE-mediated allergy. Cow’s milk and egg allergy are common childhood allergies. Until recently, children with food allergy were advised to avoid all dietary exposure to the allergen to which they were sensitive, in the thought that consumption would exacerbate their allergy. However, recent publications indicate that up to 70% of children with egg allergy can tolerate egg baked in a cake or muffin without apparent reaction. Likewise, up to 75% of children can tolerate baked goods containing cow’s milk, and these children demonstrate IgE and IgG4 profiles indicative of tolerance development. This article will review the current literature regarding the use of heated food allergens as immunotherapy for children with cow’s milk and egg allergy.
doi:10.3390/nu5062028
PMCID: PMC3725491  PMID: 23739144
egg; milk; allergy; heated allergens; tolerance; oral; immunotherapy
9.  Development of the Chicago Food Allergy Research Surveys: assessing knowledge, attitudes, and beliefs of parents, physicians, and the general public 
Background
Parents of children with food allergy, primary care physicians, and members of the general public play a critical role in the health and well-being of food-allergic children, though little is known about their knowledge and perceptions of food allergy. The purpose of this paper is to detail the development of the Chicago Food Allergy Research Surveys to assess food allergy knowledge, attitudes, and beliefs among these three populations.
Methods
From 2006–2008, parents of food-allergic children, pediatricians, family physicians, and adult members of the general public were recruited to assist in survey development. Preliminary analysis included literature review, creation of initial content domains, expert panel review, and focus groups. Survey validation included creation of initial survey items, expert panel ratings, cognitive interviews, reliability testing, item reduction, and final validation. National administration of the surveys is ongoing.
Results
Nine experts were assembled to oversee survey development. Six focus groups were held: 2/survey population, 4–9 participants/group; transcripts were reviewed via constant comparative methods to identify emerging themes and inform item creation. At least 220 participants per population were recruited to assess the relevance, reliability, and utility of each survey item as follows: cognitive interviews, 10 participants; reliability testing ≥ 10; item reduction ≥ 50; and final validation, 150 respondents.
Conclusion
The Chicago Food Allergy Research surveys offer validated tools to assess food allergy knowledge and perceptions among three distinct populations: a 42 item parent tool, a 50 item physician tool, and a 35 item general public tool. No such tools were previously available.
doi:10.1186/1472-6963-9-142
PMCID: PMC2736935  PMID: 19664230
10.  Epidemiological Change of Atopic Dermatitis and Food Allergy in School-Aged Children in Korea between 1995 and 2000 
Journal of Korean Medical Science  2004;19(5):716-723.
Little is known about the prevalence of atopic dermatitis and food allergy outside North America and Europe. We evaluated the prevalence of atopic dermatitis and food allergy with the comparison of prevalence between 1995 and 2000 in Korea and evaluated the correlation of prevalence between atopic dermatitis and food allergy. A cross-sectional questionnaire survey was conducted on random samples of schoolchildren 6 to 14 yr at two time points, 1995 and 2000 throughout Korea. The last twelve months prevalence of atopic dermatitis in Korean school-aged children was increased from 1995 to 2000. The twelve-month prevalence of atopic dermatitis and food allergy were higher in Seoul than in any other provincial cities in 1995, but the prevalence of both diseases in Seoul and Provincial Centers became to be similar in 2000. The rate responded to food allergy of children with atopic dermatitis (9.5%) was lower than that of the western countries (60%). And our data demonstrated paternal and maternal allergy history is very significantly correlated to developing atopic dermatitis in their offspring. The further objective evaluations are required to confirm these outcomes because the environmental and risk factors may be different among the countries according to their living cultures.
doi:10.3346/jkms.2004.19.5.716
PMCID: PMC2816337  PMID: 15483350
Dermatitis, Atopic; Food Hypersensitivity; Prevalence
11.  Food allergies in developing and emerging economies: need for comprehensive data on prevalence rates 
Although much is known today about the prevalence of food allergy in the developed world, there are serious knowledge gaps about the prevalence rates of food allergy in developing countries. Food allergy affects up to 6% of children and 4% of adults. Symptoms include urticaria, gastrointestinal distress, failure to thrive, anaphylaxis and even death. There are over 170 foods known to provoke allergic reactions. Of these, the most common foods responsible for inducing 90% of reported allergic reactions are peanuts, milk, eggs, wheat, nuts (e.g., hazelnuts, walnuts, almonds, cashews, pecans, etc.), soybeans, fish, crustaceans and shellfish. Current assumptions are that prevalence rates are lower in developing countries and emerging economies such as China, Brazil and India which raises questions about potential health impacts should the assumptions not be supported by evidence. As the health and social burden of food allergy can be significant, national and international efforts focusing on food security, food safety, food quality and dietary diversity need to pay special attention to the role of food allergy in order to avoid marginalization of sub-populations in the community. More importantly, as the major food sources used in international food aid programs are frequently priority allergens (e.g., peanut, milk, eggs, soybean, fish, wheat), and due to the similarities between food allergy and some malnutrition symptoms, it will be increasingly important to understand and assess the interplay between food allergy and nutrition in order to protect and identify appropriate sources of foods for sensitized sub-populations especially in economically disadvantaged countries and communities.
doi:10.1186/2045-7022-2-25
PMCID: PMC3551706  PMID: 23256652
Food allergy; Food hypersensitivity; Nutrition; Developing countries
12.  Demographic Predictors of Peanut, Tree Nut, Fish, Shellfish, and Sesame Allergy in Canada 
Journal of Allergy  2011;2012:858306.
Background. Studies suggest that the rising prevalence of food allergy during recent decades may have stabilized. Although genetics undoubtedly contribute to the emergence of food allergy, it is likely that other factors play a crucial role in mediating such short-term changes. Objective. To identify potential demographic predictors of food allergies. Methods. We performed a cross-Canada, random telephone survey. Criteria for food allergy were self-report of convincing symptoms and/or physician diagnosis of allergy. Multivariate logistic regressions were used to assess potential determinants. Results. Of 10,596 households surveyed in 2008/2009, 3666 responded, representing 9667 individuals. Peanut, tree nut, and sesame allergy were more common in children (odds ratio (OR) 2.24 (95% CI, 1.40, 3.59), 1.73 (95% CI, 1.11, 2.68), and 5.63 (95% CI, 1.39, 22.87), resp.) while fish and shellfish allergy were less common in children (OR 0.17 (95% CI, 0.04, 0.72) and 0.29 (95% CI, 0.14, 0.61)). Tree nut and shellfish allergy were less common in males (OR 0.55 (95% CI, 0.36, 0.83) and 0.63 (95% CI, 0.43, 0.91)). Shellfish allergy was more common in urban settings (OR 1.55 (95% CI, 1.04, 2.31)). There was a trend for most food allergies to be more prevalent in the more educated (tree nut OR 1.90 (95% CI, 1.18, 3.04)) and less prevalent in immigrants (shellfish OR 0.49 (95% CI, 0.26, 0.95)), but wide CIs preclude definitive conclusions for most foods. Conclusions. Our results reveal that in addition to age and sex, place of residence, socioeconomic status, and birth place may influence the development of food allergy.
doi:10.1155/2012/858306
PMCID: PMC3236463  PMID: 22187574
13.  Food Allergy Education for School Nurses: A Needs Assessment Survey by the Consortium of Food Allergy Research 
Food allergy is increasing in school-age children. School nurses are a primary health care resource for children with food allergy and must be prepared to manage allergen avoidance and respond in the event of an allergic reaction. An anonymous survey was administered to school nurses attending their association meetings to determine their educational needs regarding children with food allergy. With 199 school nurses responding, their self-reported proficiency for critical areas of food allergy knowledge and management varied, with weaknesses identified particularly for emergency plan development, staff education, delegation, developing guidelines for banning foods and planning school trips. Nurses reported a high interest in obtaining educational materials in these areas and prefer video and Internet resources that could be promoted through professional organizations.
doi:10.1177/1059840510369482
PMCID: PMC3888215  PMID: 20404357
school nurses; food allergy; education; emergency plan
14.  Tree Nut Allergy, Egg Allergy, and Asthma in Children 
Clinical pediatrics  2010;50(2):133-139.
Background
Children with food allergies often have concurrent asthma.
Objective
The authors aimed to determine the prevalence of asthma in children with food allergies and the association of specific food allergies with asthma.
Methods
Parental questionnaire data regarding food allergy, corroborated by allergic sensitization were completed for a cohort of 799 children with food allergies. Multivariate regression analysis tested the association between food allergy and reported asthma.
Results
In this cohort, the prevalence of asthma was 45.6%. After adjusting for each food allergy, environmental allergies, and family history of asthma, children with egg allergy (odds ratio [OR] = 2.0; 95% confidence interval [CI] = 1.3–3.2; P < .01) or tree nut allergy (OR = 2.0; 95% CI = 1.1–3.6; P = .02) had significantly greater odds of report of asthma.
Conclusion
There is a high prevalence of asthma in the food-allergic pediatric population. Egg and tree nut allergy are significantly associated with asthma, independent of other risk factors.
doi:10.1177/0009922810384720
PMCID: PMC3070157  PMID: 21098525
asthma; food allergy; food hypersensitivity; nut allergy; nut hypersensitivity; egg allergy; egg hypersensitivity; pediatrics; allergy; asthma epidemiology
15.  Food allergy 
Korean Journal of Pediatrics  2012;55(5):153-158.
Food allergy is an important public health problem affecting 5% of infants and children in Korea. Food allergy is defined as an immune response triggered by food proteins. Food allergy is highly associated with atopic dermatitis and is one of the most common triggers of potentially fatal anaphylaxis in the community. Sensitization to food allergens can occur in the gastrointestinal tract (class 1 food allergy) or as a consequence of cross reactivity to structurally homologous inhalant allergens (class 2 food allergy). Allergenicity of food is largely determined by structural aspects, including cross-reactivity and reduced or enhanced allergenicity with cooking that convey allergenic characteristics to food. Management of food allergy currently focuses on dietary avoidance of the offending foods, prompt recognition and treatment of allergic reactions, and nutritional support. This review includes definitions and examines the prevalence and management of food allergies and the characteristics of food allergens.
doi:10.3345/kjp.2012.55.5.153
PMCID: PMC3362728  PMID: 22670149
Food allergy; Allergens; Cross reactions; Disease management
16.  Health-related quality of life among adolescents with allergy-like conditions – with emphasis on food hypersensitivity 
Background
It is known that there is an increase in the prevalence of allergy and that allergic diseases have a negative impact on individuals' health-related quality of life (HRQL). However, research in this field is mainly focused on individuals with verified allergy, i.e. leaving out those with self-reported allergy-like conditions but with no doctor-diagnosis. Furthermore, studies on food hypersensitivity and quality of life are scarce. In order to receive information about the extent to which adolescent females and males experience allergy-like conditions and the impact of these conditions on their everyday life, the present study aimed to investigate the magnitude of self-reported allergy-like conditions in adolescence and to evaluate their HRQL. Special focus was put on food hypersensitivity as a specific allergy-like condition and on gender differences.
Methods
In connection with lessons completed at the children's school, a study-specific questionnaire and the generic instrument SF-36 were distributed to 1488 adolescents, 13–21 years old (response rate 97%).
Results
Sixty-four per cent of the respondents reported some kind of allergy-like condition: 46% reported hypersensitivity to defined substances and 51% reported allergic diseases (i.e. asthma/wheezing, eczema/rash, rhino-conjunctivitis). A total of 19% reported food hypersensitivity. Females more often reported allergy-like conditions compared with males (p < 0.001). The adolescents with allergy-like conditions reported significantly lower HRQL (p < 0.001) in seven of the eight SF-36 health scales compared with adolescents without such conditions, regardless of whether the condition had been doctor-diagnosed or not. Most adolescents suffered from complex allergy-like conditions.
Conclusions
The results indicate a need to consider the psychosocial impact of allergy-like conditions during school age. Further research is needed to elucidate the gender differences in this area. A team approach addressing better understanding of how allergy-like conditions impair the HRQL may improve the management of the adolescent's health problems, both in health-care services and in schools.
doi:10.1186/1477-7525-2-65
PMCID: PMC534793  PMID: 15555064
Health-related quality of life; hypersensitivity; allergic disease; food hypersensitivity; adolescence; gender
17.  Role of selenium and zinc in the pathogenesis of food allergy in infants and young children 
Archives of Medical Science : AMS  2012;8(6):1083-1088.
Introduction
Selenium and zinc are indispensable microelements for normal functioning and development of the human body. They are cofactors of many enzymes of the antioxidative barrier (selenium – glutathione peroxidase; zinc – superoxide dismutase). The aim of the study was to evaluate the importance of selenium and zinc in the pathogenesis of food allergy in small children.
Material and methods
The study was performed in 134 children with food allergy, aged 1 to 36 months. The control group was composed of 36 children at the same age, without clinical symptoms of food intolerance. Each child had estimated serum levels of zinc and selenium. Furthermore, the authors evaluated activity of glutathione peroxidase (GSH-Px) in erythrocyte lysates and serum. Tests were performed twice, before and after 6-month administration of elimination diet.
Results
The obtained results showed that children with food allergy had significantly lower concentrations of selenium, zinc and examined enzymes in comparison to children from the control group. Concentration of selenium and zinc as well as activity of examined enzymes increased after application of eliminative diet.
Conclusions
In children with allergy decreased concentrations of selenium and zinc, and lower values of glutathione peroxidase and superoxide dismutase which increased after elimination diet were affirmed. These observations suggest their role in pathogenesis of food allergy. Conducted observations indicate the need to monitor trace elements content in the diet in children with food allergy. The results showed that children with food allergy had a weakened antioxidative barrier.
doi:10.5114/aoms.2012.32420
PMCID: PMC3542500  PMID: 23319985
selenium; zinc; food allergy; small children
18.  Safety and feasibility of oral immunotherapy to multiple allergens for food allergy 
Background
Thirty percent of children with food allergy are allergic to more than one food. Previous studies on oral immunotherapy (OIT) for food allergy have focused on the administration of a single allergen at the time. This study aimed at evaluating the safety of a modified OIT protocol using multiple foods at one time.
Methods
Participants underwent double-blind placebo-controlled food challenges (DBPCFC) up to a cumulative dose of 182 mg of food protein to peanut followed by other nuts, sesame, dairy or egg. Those meeting inclusion criteria for peanut only were started on single-allergen OIT while those with additional allergies had up to 5 foods included in their OIT mix. Reactions during dose escalations and home dosing were recorded in a symptom diary.
Results
Forty participants met inclusion criteria on peanut DBPCFC. Of these, 15 were mono-allergic to peanut and 25 had additional food allergies. Rates of reaction per dose did not differ significantly between the two groups (median of 3.3% and 3.7% in multi and single OIT group, respectively; p = .31). In both groups, most reactions were mild but two severe reactions requiring epinephrine occurred in each group. Dose escalations progressed similarly in both groups although, per protocol design, those on multiple food took longer to reach equivalent doses per food (median +4 mo.; p < .0001).
Conclusions
Preliminary data show oral immunotherapy using multiple food allergens simultaneously to be feasible and relatively safe when performed in a hospital setting with trained personnel. Additional, larger, randomized studies are required to continue to test safety and efficacy of multi-OIT.
Trial registration
Clinicaltrial.gov NCT01490177
doi:10.1186/1710-1492-10-1
PMCID: PMC3913318  PMID: 24428859
Food allergy; Oral immunotherapy (OIT); Specific oral tolerance induction (SOTI); Multiple; Safety; Efficacy
19.  Food intolerance and food allergy in children: a review of 68 cases. 
Archives of Disease in Childhood  1982;57(10):742-747.
The clinical and laboratory features of 68 children with food intolerance or food allergy are reviewed. Young children were affected the most with 79% first experiencing symptoms before age 1 year. Forty-eight (70%) children presented with gastrointestinal symptoms (vomiting, diarrhoea, colic, abdominal pain, failure to thrive), 16 (24%) children with skin manifestations (eczema, urticaria, angioneurotic oedema, other rashes), and 4 (6%) children with wheeze. Twenty-one children had failed to thrive before diagnosis. A single food (most commonly cows' milk) was concerned in 28 (41%) cases. Forty (59%) children had multiple food intolerance or allergy; eggs, cows' milk, and wheat were the most common. Diagnosis was based on observing the effect of food withdrawal and of subsequent rechallenge. In many children food withdrawal will mean the use of an elimination diet which requires careful supervision by a dietician. Laboratory investigations were often unhelpful in suggesting or confirming the diagnosis.
PMCID: PMC1627921  PMID: 7138062
20.  Eczema 
Clinical Evidence  2011;2011:1716.
Introduction
Eczema, as defined by the World Allergy Organization (WAO) revised nomenclature in 2003, affects 15% to 20% of school children and 2% to 5% of adults worldwide. About 50% of people with eczema demonstrate atopy, with specific immunoglobulin E responses to allergens.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of topical medical treatments, and dietary interventions in adults and children with established eczema? What are the effects of breastfeeding, reducing allergens, or dietary interventions for primary prevention of eczema in predisposed infants? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 54 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: breastfeeding, controlling house dust mites, corticosteroids, dietary exclusion of eggs or cow's milk, elementary diets, emollients, essential fatty oils, few-foods diet, multivitamins, pimecrolimus, probiotics, pyridoxine, reducing maternal dietary allergens, tacrolimus, vitamin E, and zinc supplements.
Key Points
Eczema, as defined by the World Allergy Organization (WAO) revised nomenclature in 2003, affects 15% to 20% of school children worldwide and 2% to 5% of adults. Only about 50% of people with eczema demonstrate allergic sensitisation. Remission occurs in two-thirds of children by the age of 15 years, but relapses may occur later.
Emollients are generally considered to be effective for treating the symptoms of eczema. However, the few small short-term RCTs that have been done so far do not confirm this. Sufficiently powered long-term RCTs are needed to clarify the role of emollients in the treatment of eczema.
Corticosteroids improve clearance of lesions and decrease relapse rates compared with placebo in adults and children with eczema, although we don't know which is the most effective corticosteroid or the most effective dosing regimen. Topical corticosteroids seem to have few adverse effects when used intermittently, but if they are of potent or very potent strength, they may cause burning, skin thinning, and telangiectasia, especially in children.
The calcineurin inhibitors pimecrolimus and tacrolimus improve clearance of lesions compared with placebo and may have a role in people in whom corticosteroids are contraindicated. They also seem suitable for topical use in body areas where the skin is particularly thin, such as the face.
CAUTION: An association has been suggested between pimecrolimus and tacrolimus and skin cancer in animal models. Although this association has not been confirmed in humans, calcineurin inhibitors should be used only when other treatments have failed.
We don't know whether vitamin E or multivitamins reduce symptoms in adults with eczema or whether pyridoxine, zinc supplementation, exclusion diets, or elemental diets are effective in children with eczema, as there are insufficient good-quality studies. Probiotics do not seem to reduce symptoms in children with established eczema. Essential fatty acids, such as evening primrose oil, blackcurrant seed oil, or fish oil, do not seem to reduce symptoms in people with eczema.
We don't know whether control of house dust mites or maternal dietary restriction can prevent the development of eczema in children. Observational data suggest that exclusive breastfeeding for at least 3 months does not reduce eczema risk and there is no evidence to suggest that exclusive breastfeeding alleviates eczema symptoms, unless a child is allergic to cow's milk protein.Introduction of probiotics in the last trimester of pregnancy and during breastfeeding may reduce the risk of eczema in the baby, although it remains unclear whether both antenatal and postnatal supplementation together yields the strongest protective effect. It is equally unclear which strains of probiotics are most effective.
PMCID: PMC3217753  PMID: 21609512
21.  Succesful treatment of food allergy with Nambudripad's Allergy Elimination Techniques (NAET) in a 3-year old: A case report 
Cases Journal  2008;1:166.
Food allergy may constitute a major burden to children and their families. A 3-year-old girl was intolerant to milk, sugar, egg white, pork meat, and other foods, causing eczema and dyspnoe. She was treated with Nambudripad's Allergy Elimnation Technique (NAET), a combination of kinesiology and acupressure. After 7 treatment sessions (within 4 weeks) she was free of symptoms. After three years, she can still eat everything without symptoms. This case report highlights the possible benefit of NAET for children with food allergy. Randomized clinical trials should be encouraged to study the effectiveness of NAET in treating food allergy.
doi:10.1186/1757-1626-1-166
PMCID: PMC2556663  PMID: 18803817
22.  The impact of pre- and postnatal exposures on allergy related diseases in childhood: a controlled multicentre intervention study in primary health care 
BMC Public Health  2013;13:123.
Background
Environmental factors such as tobacco exposure, indoor climate and diet are known to be involved in the development of allergy related diseases. The aim was to determine the impact of altered exposure to these factors during pregnancy and infancy on the incidence of allergy related diseases at 2 years of age.
Methods
Children from a non-selected population of mothers were recruited to a controlled, multicenter intervention study in primary health care. The interventions were an increased maternal and infant intake of n-3 PUFAs and oily fish, reduced parental smoking, and reduced indoor dampness during pregnancy and the children’s first 2 years of life. Questionnaires on baseline data and exposures, and health were collected at 2 years of age.
Results
The prevalence of smoking amongst the mothers and fathers was approximately halved at 2 years of age in the intervention cohort compared to the control cohort. The intake of n-3 PUFA supplement and oily fish among the children in the intervention cohort was increased. There was no significant change for indoor dampness. The odds ratio for the incidence of asthma was 0.72 (95% CI, 0.55-0.93; NNTb 53), and 0.75 for the use of asthma medication (95% CI, 0.58-0.96). The odds ratio for asthma among girls was 0.41 (95% CI 0.24-0.70; NNTb 32), and for boys 0.93 (95% CI 0.68-1.26). There were no significant change for wheeze and atopic dermatitis.
Conclusion
Reduced tobacco exposure and increased intake of oily fish during pregnancy and early childhood may be effective in reducing the incidence of asthma at 2 years of age. The differential impact in boys and girls indicates that the pathophysiology of asthma may depend on the sex of the children.
Trial registration
Current Controlled Trials ISRCTN28090297.
doi:10.1186/1471-2458-13-123
PMCID: PMC3582458  PMID: 23394141
Asthma; Atopic; Dermatitis; Infant; Primary prevention; Public health
23.  493 The Prevalence of Food Allergy in Children under 2 Years in Three Cities in China 
The World Allergy Organization Journal  2012;5(Suppl 2):S173-S174.
Background
To estimate the prevalence and clinical features of food allergy in children aged 0 to 2 years.
Methods
From January to February, 2009 and January to May, 2010, all well-infants and young children between the age of 0-2 years attending routine health visits at the Department of Primary Child Care, in Chongqing, Zhuhai and Hangzhou were invited to participate the study. Parents completed questionnaires and all children were skin prick tested to a panel of 10 foods (egg white, egg yolk, cow milk, soybean, peanut, wheat, fish, shrimp, orange and carrot). Based on the results of SPT and medical history, the subjects should undergo the suspected food elimination and oral food challenge under medical supervision. Food allergy was confirmed by the food challenge test.
Results
There were 1,687 children recruited by the consent of their parents. Of 1,687 children approached, 1,604 (550 for Chongqing, 573 for Zhuhai and 481 for Hangzhou) fulfilled the study criteria for diagnosing food allergy. 100 children were confirmed to have challenge-proven food allergy in 3 cities (40 for Chongqing, 33 for Zhuhai and 27 for Hangzhou). The prevalence of food allergy in 0 to 2 years old children in Chongqing was 7.3%, in Zhuhai was 5.8% and in Hangzhou was 5.5%. There was no significant difference in the prevalence of food allergy in children under 2 years among the 3 cities, and the average prevalence for food allergy in children under 2 years was 6.2%. Egg was the most common allergen, followed by cow milk.
Conclusions
The prevalence of food allergy in 0 to 2 years old children in China was 5.5% to 7.3%. There was no significant difference in the prevalence of food allergy in children under 2 years among the 3 cities. Egg was the most common allergen, followed by cow milk.
doi:10.1097/01.WOX.0000411608.35185.f5
PMCID: PMC3512627
24.  Food Allergy and Increased Asthma Morbidity in a School-Based Inner-City Asthma Study 
Background
Children with asthma have increased prevalence of food allergies. The relationship between food allergy and asthma morbidity is unclear.
Objective
We aimed to investigate the presence of food allergy as an independent risk factor for increased asthma morbidity using the School Inner-City Asthma (SICAS), a prospective study evaluating risk factors and asthma morbidity among urban children.
Methods
We prospectively surveyed 300 children from inner-city schools with physician-diagnosed asthma, followed by clinical evaluation. Food allergies were reported including symptoms experienced within one hour of food ingestion. Asthma morbidity, pulmonary function, and resource utilization were compared between children with food allergies and without.
Results
Seventy-three (24%) of 300 asthmatic children surveyed had physician- diagnosed food allergy, and 36 (12%) had multiple food allergies. Those with any food allergy independently had increased risk of hospitalization (OR: 2.35, 95% CI: 1.30–4.24, p=0.005), and use of controller medication (OR: 1.99, 95% CI: 1.06–3.74, p=0.03). Those with multiple food allergies also had an independently higher risk of hospitalization in the past year (OR: 4.10 95% CI: 1.47–11.45, p=0.007), asthma-related hospitalization (OR: 3.52, 95% CI: 1.12–11.03, p=0.03), controller medication use (OR: 2.38 95% CI: 1.00–5.66, p=0.05), and more provider visits (median 4.5 versus 3.0, p=0.008). Furthermore, lung function was significantly lower (% predicted FEV1 and FEV1/FVC ratios) in both food allergy category groups.
Conclusions
Food allergy is highly prevalent in inner-city school-aged children with asthma. Children with food allergies have increased asthma morbidity and health resource utilization with decreased lung function, and this association is stronger in those with multiple food allergies.
doi:10.1016/j.jaip.2013.06.007
PMCID: PMC3777668  PMID: 24058900
asthma; food allergy; hospitalization; morbidity; prevalence; resource utilization; risk
25.  Predictive value of specific IgE for clinical peanut allergy in children: relationship with eczema, asthma, and setting (primary or secondary care) 
The usefulness of peanut specific IgE levels for diagnosing peanut allergy has not been studied in primary and secondary care where most cases of suspected peanut allergy are being evaluated. We aimed to determine the relationship between peanut-specific IgE levels and clinical peanut allergy in peanut-sensitized children and how this was influenced by eczema, asthma and clinical setting (primary or secondary care). We enrolled 280 children (0–18 years) who tested positive for peanut-specific IgE (> 0.35 kU/L) requested by primary and secondary physicians. We used predefined criteria to classify participants into three groups: peanut allergy, no peanut allergy, or possible peanut allergy, based on responses to a validated questionnaire, a detailed food history, and results of oral food challenges.
Fifty-two participants (18.6%) were classified as peanut allergy, 190 (67.9%) as no peanut allergy, and 38 (13.6%) as possible peanut allergy. The association between peanut-specific IgE levels and peanut allergy was significant but weak (OR 1.46 for a 10.0 kU/L increase in peanut-specific IgE, 95% CI 1.28-1.67). Eczema was the strongest risk factor for peanut allergy (aOR 3.33, 95% CI 1.07-10.35), adjusted for demographic and clinical characteristics. Asthma was not significantly related to peanut allergy (aOR 1.93, 95% CI 0.90-4.13). Peanut allergy was less likely in primary than in secondary care participants (OR 0.46, 95% CI 0.25-0.86), at all levels of peanut-specific IgE.
The relationship between peanut-specific IgE and peanut allergy in children is weak, is strongly dependent on eczema, and is weaker in primary compared to secondary care. This limits the usefulness of peanut-specific IgE levels in the diagnosis of peanut allergy in children.
doi:10.1186/2045-7022-3-34
PMCID: PMC3852137  PMID: 24112405
Peanut allergy; Peanut-specific IgE; Peanut sensitization; Eczema; Asthma; Children; Teenagers

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