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Food allergy and atopic eczema
Abstract
To review recent developments on the inter-relationship between food allergy and atopic eczema, with a particular focus on understanding the role of filaggrin gene defects.
Filaggrin gene defects have recently been identified as a major risk factor for the development of atopic eczema. These skin barrier defects increase the risk of early onset, severe and persistent forms of atopic eczema. They also increase the risk of allergic sensitization, and asthma and allergic rhinitis in those with co-existent eczema. These skin barrier defects are also likely to increase the risk of food allergy.
Atopic dermatitis and food allergy are frequently herald conditions for other manifestations of 'the allergic march'. They commonly co-exist, particularly in those with early onset, severe and persistent atopic eczema. Filaggrin gene defects substantially increase the risk of atopic eczema. The increased skin permeability may increase the risk of sensitization to food and other allergens, this pointing to the possible role of cutaneous allergen avoidance in early life to prevent the onset of atopic eczema and food allergy. Emerging evidence also indicates that oral exposure to potentially allergenic foods may be important for inducing immunological tolerance.
... Tanto la dermatitis atópica (DA) como la alergia alimentaria (AA) son condiciones que con frecuencia señalan el comienzo de la denominada "marcha alérgica", que se caracteriza por diferentes manifestaciones atópicas relacionadas y sucesivas a lo largo de la vida del individuo. Comúnmente DA y AA coexisten en mayor medida en los pacientes que presentan DA de comienzo precoz, agresiva y persistente [1][2][3] . ...
... Las cifras de prevalencia se han incrementado 2 a 3 veces durante las tres últimas décadas en países industrializados. La amplia variación en la prevalencia dada principalmente entre las zonas urbanas y rurales identificadas dentro de la población de un mismo país, incluso en grupos étnicos similares, sugiere que los factores ambientales determinan en gran medida la expresión de la DA 1,2,9,10 . ...
The term "allergic march" refers to the history of different atopic manifestations throughout the patient's life. Children with food allergy (FA) are more predisposed to the development of other allergic diseases such as atopic dermatitis (AD), asthma and allergic rhinitis. AlD and FA coexist to a greater extent in patients with early signs of AD, aggressive and persistent symptoms. Meanwhile, FA is a precipitating factor to AlD especially in patients with IgE-mediated FA. Correlation to delayed manifestations of FA may also be found. Epithelial barrier dysfunction, mainly attributed to mutations in the filaggrin gene, has been described as a possible trigger for allergen sensitization by increasing skin permeability. This study describes general characteristics of DA and current research evidence regarding the role of FA in the DA development, management and prevention strategies. Also, the utility of diagnostic tests, treatment and prevention in children with DA and FA are discussed. The restoration of impaired skin barrier to prevent sensitization to antigens may have an important role to prevent the development of allergic diseases, especially respiratory diseases.
... Dupilumab is another biologic agent that has been studied for the treatment of FAs, either as monotherapy or in combination with AIT [54 & ]. The biological effects of the cytokines IL-4 and IL-13, which are critical drivers of the TH2 response, are inhibited by dupilumab [55]. An ongoing phase II trial in children (aged 6-17 years) with peanut allergy (NCT03682770), aims to assess the treatment's tolerability at week 24 of the combination of dupilumab with peanut immunotherapy (AR101) or placebo. ...
Purpose of review
This review aims to provide an overview of the current and future treatment options for children with food allergies (FAs), highlighting the latest research findings and the potential impact of these new approaches on improving patients’ and caregivers’ quality of life.
Recent findings
In the last decade, many promising approaches have emerged as an alternative to the standard avoidance of the culprit food with the risk of severe accidental reactions. Desensitization through oral immunotherapy has been introduced in clinical settings as a therapeutic approach, and more recently also omalizumab. In addition, alternative routes of administration for immunotherapy, other biologics, small molecules, probiotics or prebiotics, microbiota transplantation therapy, IGNX001, and PVX108 are being investigated.
Summary
The portfolio of available treatment options for food allergies is increasing but several relevant unmet needs remain. This review aims to provide a brief overview of the existing and future treatment options for IgE-mediated food allergies.
... Other factors suggested to be involved are female sex, young age, eosinophilia (associated with tacrolimus and with Epstein-Barr virus [EBV] infection, along with increased IgE levels) and positive PCR results for EBV (possibly related to overimmunosuppression or to the development of T H 2 predominance). On the other hand, no correlation has been found between resolution and time to development, organ type, acute rejection, compatibility, or other infectious diseases [3,16,72,73]. ...
De novo food allergy is a common phenomenon among pediatric solid organ recipients (8.5%-57%) when compared with the general population (0.45%-10%). Other associated disorders include non–IgE mediated immune reactions and clinical predisposition to asthma and alterations in the oral mucosa. Originally, passive mechanisms (passive transfer of IgE and immune cells) were thought to be responsible for acute, transient cases of food allergies with a previous history of sensitization for a specific allergen in the donor. Recently proposed pathophysiological mechanisms to explain de novo allergies include TH2/B-cell imbalance, regulatory T-cell (Treg) disruption, gastrointestinal immaturity, and altered gastrointestinal permeability. Recent studies also suggest that immunosuppressive drugs, especially tacrolimus, promote naïve T-cell differentiation into TH2 cells, IgE-promoting cytokine production, decreased IL-5 and IL-10 levels, increased IgA levels, and Treg disruption. Such immunological interactions, in conjunction with altered intestinal permeability, intestinal immaturity in children, history of viral infection, and a personal history of allergies or eczema, are thought to explain most clinical cases of pediatric de novo food allergy after solid organ transplantation reported in the literature. A better understanding of the immunological mechanisms underpinning organ donors and recipients may unveil some of the caveats concerning therapeutic management and improve the quality of life of affected individuals.
... In most patients, both conditions are transient and improve spontaneously in adolescence. Only a small percentage of adult patients who persist with AD have simultaneous FA [16,17] . AD and FA coexist predominantly in patients with early, aggressive, and persistent onset of AD [16,18,19] . ...
Background: Atopic dermatitis is a chronic, inflammatory, and pruritic dermatosis of high prevalence, especially in childhood. a relevant public health issue. Atopic dermatitis is associated with several factors, including genetic, psychological, infectious, food, and environmental, and may be associated with other manifestations of atopy, such as asthma and rhinitis. Objective: To determine the epidemiological profile and the prevalence of personal and family history of allergy in children with atopic dermatitis at a referral service, comparing it to existing literature. Methods: We conducted a cross-sectional and descriptive hospital-based study involving children of both genders under 18 years with clinical diagnosis of atopic dermatitis (Hanifin and Rajka criteria) seen at the Pediatric Dermatology Outpatient Clinic of Hospital Municipal Universitário de Taubaté (HMUT), SP-Brazil, from October 2018 to April 2019. Epidemiological data and data related to personal and family history of allergies were collected from the medical records. Microsoft Excel 2019 was used for compilation and data analysis. Results: Of the 440 consultations in that period, 35 (7.9%) were for atopic dermatitis, of which 23 of them were females (65.7%) and 15 were phototype IV (42.9%); their mean age was 7.7 (standard deviation = 4.3), and the duration of disease ranged from 2 months to 14 years (mean 5.3 years; standard deviation = 4.3). Among the 35 patients, 31 (88.6%) manifested the condition by the fifth year of life. Personal history of allergies was observed in 27 individuals (77.1%), with a predominance of allergic rhinitis and in older age groups. Conclusion: This study, as a pioneer in the region, contributes to the epidemiological profile of patients with atopic dermatitis from the Pediatric Dermatology Outpatient Clinic of HMUT, revealing an early onset and a higher prevalence in females and individuals with higher phototypes. In addition, this study also demonstrated the prevalence of personal and family history of allergies in these patients, consistent with literature.
... ,3 Dupilumab treatment in AD patients reduces total serum IgE; however, the course of specific IgE (sIgE) levels for food allergens during dupilumab treatment has not been defined yet. 1 Therefore, the aim of this study was to investigate the effect of dupilumab on sIgE levels in patients with moderate-to-severe AD with comorbid food allergy. ...
... Changes in this gene are thought to play a key role in cutaneous exposure to food allergies, by increasing the permeability of the skin to proteins. 8 Food allergies often accompany AD, which is very common in children. It is known that genetic factors play a role. ...
Objective: To determine the frequency and type of food allergy in patients having atopic dermatitis and to show the presence of mutations genetically. Methods: Patients diagnosed as having atopic dermatitis according to the Hanifin Rajka criteria were evaluated retrospectively. Eosinophils, total immunoglobin E, milk-specific immunoglobulin E, egg-specific immunoglobulin E, wheat-specific immunoglobulin E, and filaggrin gene mutation results were recorded. Nutrient elimination was performed for 1 month in patients who were thought to have food allergy owing to skin prick test and milk-specific immunoglobulin E results. The diagnosis was confirmed through a food loading test for the patients who benefited from the elimination. Results: Of the 66 patients included in the study, 42 (63.63%) were male. Food allergies were detected in 40 patients (60.6%). According to the Scoring of Atopic Dermatitis index, 9 out of 16 patients aged 40 years and over had food allergy and 31 out of 50 patients aged under 40 years had food allergy. There was no significant difference between the groups (P=.56). All patients included in the study were examined for filaggrin. Only 1 patient with a Scoring of Atopic Dermatitis index below 40 and milk allergy was found to have p.R501 * and c.2282-2285delCAGT mutations. Conclusion: Atopic dermatitis food allergy was found to be 60.6%. The most common improvement was egg allergy and egg elimination. There was no difference between atopic dermatitis severity and food allergy and laboratory tests. Severe atopic dermatitis was found to be 24.2%.
... Pacientes adultos que persistem com DA, apenas uma pequena porcentagem apresentam AA simultaneamente. 16,17 A DA e a AA coexistem predominantemente em pacientes com início precoce, agressivo e persistente da DA. 16,18,19 A AA é considerada fator agravante de DA, especialmente AA mediada por IgE. 16 Histórico familiar para condições alérgicas outras que não a DA também é frequentemente referido na literatura, porém raramente mensurado, e em conjunto com o exposto acima motivou o presente estudo que objetivou: determinar o perfil epidemiológico e a prevalência de antecedentes pessoais e de histórico familiar de alergia em pacientes portadores de DA atendidos em um Serviço de Referência, comparando com dados da literatura. ...
Introdução: A dermatite atópica é uma dermatose crónica, inflamatória e pruriginosa de alta prevalência, principalmente na infância, constituindo um problema relevante para a saúde pública. Diversos fatores se associam a um maior risco para dermatite atópica: genéticos, psicológicos, infecciosos, alimentares, ambientais, entre outros e a dermatite atópica pode estar associada a outras manifestações de atopia, como asma e rinite.
Este estudo objetivou determinar o perfil epidemiológico e a prevalência de antecedentes pessoais e familiares de alergia em crianças com dermatite atópica atendidas num serviço de referência, comparando à literatura existente.
Métodos: Estudo transversal e descritivo, de base hospitalar, envolvendo crianças de ambos os gêneros com menos de 18 anos com diagnóstico clínico de dermatite atópica (critérios de Hanifin e Rajka) atendidas no Ambulatório de Dermatologia Pediátrica do Hospital Municipal Universitá- rio de Taubaté (H.MUT), SP – Brasil, de outubro de 2018 a abril de 2019. Foram colhidos dados epidemiológicos e relacionados com o histórico pessoal e familiar de alergias obtidos por levantamento de prontuários. Microsoft Excel 2019 utilizado para análise e compilação dos dados.
Resultados: Dos 440 atendimentos realizados no período, 35 (7,9%) foram de dermatite atópica, 23 no sexo feminino (65,7%), 15 de fototipo IV (42,9%) com idade média 7,7 anos (desvio padrão=4,3), com duração de doença de 2 meses a 14 anos (média 5,3 anos – desvio padrão=4,3). Trinta e um pacientes (88,6%) manifestaram o quadro até o quinto ano de vida. Histórico pessoal de alergias estava presente em 77,1% (27 in- divíduos), com predomínio da rinite alérgica e em faixas etárias mais elevadas. Histórico familiar positivo em 62,9% (22 indivíduos).
Conclusão: Estudo pioneiro na região, permitiu determinar o perfil epidemiológico dos pacientes portadores de dermatite atópica do Ambulatório de Dermatologia Pediátrica do H.MUT, revelando início precoce e maior prevalência no sexo feminino e em fototipo alto. Além disso, identificou a prevalência de antecedentes pessoais e de histórico familiar de alergia nesses pacientes, dados concordes com a literatura.
... The association between allergen sensitization and atopic diseases have been well demonstrated 5,6 . Clinically, food sensitization appears to be associated with eczema, whereas mite sensitization is strongly related to rhinitis and asthma 7,8 . However, total serum IgE level is considered as a high sensitivity predictor of atopic diseases 9 . ...
There are few studies addressing the longitudinal analysis of serum IgE levels and its impact to the development of atopic diseases in early childhood. We investigated 170 children who regularly followed up at our clinic for 4 years in a birth cohort study with at least 3 time-points of serum samples. The pattern of total serum IgE levels from 6 months to 4 years of age was clustered using K-means method in R software. Specific immunoglobulin E antibodies against food (egg white and milk) and inhalant allergens (D. pteronyssinus and D. farinae) were measured at 0.5, 1, 1.5, 2, 3 and 4 years of age. By using K-means clustering, the dynamic changes in serum IgE levels was significantly stratified into 3 clusters (cluster A, < 100 kU/L, n = 106; cluster B, 100–200 kU/L, n = 35; cluster C, ≥ 200 kU/L, n = 29). A persistent total IgE levels higher than 100 kU/L appeared to be associated with higher prevalence of sensitization to food but not mite. However, a persistent IgE levels higher than 200 kU/L was not only remarkably related to increased prevalence of mite sensitization, but also risk of eczema at age 1 and allergic rhinitis and asthma at age 2, 3 and 4. In conclusion, a persistent total serum IgE level ≥ 200 kU/L since infancy is strongly associated with the presence of food and mite sensitization, as well as the development of eczema in infants, and rhinitis and asthma later in early childhood.
... The allergic march concept suggests the temporal progression to asthma comes mainly from atopic dermatitis (eczema) [25]. The concept contends that the coexistence of atopic dermatitis and food allergy especially in those with early-onset and severe eczema heralds the development of other allergic conditions such as asthma [26]. The existing literature is still controversial on whether early life food sensitization is the first step towards food allergy, which may lead to asthma and other allergic conditions. ...
Asthma is a chronic respiratory disease which is associated with higher levels of systemic inflammation. The causes of asthma remain poorly understood. Unhealthy diet and food allergy are potential risk factors for developing asthma. The prevalence of asthma in the Arabian Gulf region (AGR), and Kuwait, Saudi Arabia and Qatar in particular, is higher than in other Eastern Mediterranean countries. In the AGR, diets tend to be of low nutritional value due to high levels of total energy, cholesterol, sodium, added sugars and saturated fat, and low levels of fiber, fruit and vegetables. A few studies that include children and adults in the AGR have suggested a potential link between unhealthy diets/specific food allergens and increased risk of asthma, however, the association of food allergy with asthma is still a controversial issue. The aim of this commentary is to consider the evidence from the AGR regarding the effects of diet/food allergy on asthma risk that may be used to make recommendations for future research.
... Coexistence of multiple allergic diseases has been widely observed in epidemiological studies [5][6][7], as well as in clinical experience [8]. Coexistence with AD and food allergy has been estimated in about 35-40% of children, especially in those with early onset and more severe and persistent disease [9]. Previous population-based studies identified some individual and environmental risk factors, like urbanization and mold exposure, associated with an higher AD prevalence in Italian children and adolescents, thus providing important insights for prevention and interventions [10,11]. ...
Background:
Atopic dermatitis (AD) represents the most common chronic inflammatory skin disease in childhood. Few data are available about the different AD phenotypes and their nationwide distribution.
Methods:
We performed a cross-sectional multicentre study involving some of the main Italian paediatric allergy centres in 9 Italian cities. A structured questionnaire was administered to 371 children with AD. Patients were divided in two groups: preschool children (aged <5 years) and schoolchildren (aged 6-14 years). A latent class analysis (LCA) was used to detect AD phenotypes and to investigate their association with risk factors and other atopic diseases.
Results:
LCA identified five AD phenotypes in preschoolers group (8% "moderate-severe AD, high comorbidity", 35% "moderate-severe AD, low comorbidity", 20% "mild AD, low comorbidity", 32% "mild AD, respiratory comorbidity", 5% "mild AD, food-induced comorbidity") and four AD phenotypes in schoolchildren (24% "moderate-severe AD, high comorbidity", 10% "moderate-severe AD, low comorbidity", 16% "mild AD, low comorbidity", 49% "mild AD, respiratory comorbidity"). Parental history of asthma and eczema, early day-care attendance and mould exposure were associated significantly to the "moderate-severe AD, high comorbidity" phenotype in preschool children (p<0.05). The "moderate-severe AD" phenotypes showed also to have the higher burden in terms of medication use and daily activities limitation.
Conclusions:
The detection of different AD phenotypes suggests the importance of a stratified approach to the management of this complex disease and the need of further studies to predict AD course and to develop more efficient therapeutic strategies.
... house dust mite and pollen grains), air chemical pollutants (e.g. exhaust fumes of cars, volatile organic compounds, nitrogen dioxide), ingredients in personal care products, and food additives have also been identified as risk factors for eczema in adults (Montnemery et al., 2003;Tanei, 2009;Worth and Sheikh, 2010); nevertheless, these factors were not assessed in this study. Prospective cohort studies of grain workers that take into account the influence of these factors on the incidence of eczema are warranted. ...
Objectives:
To examine the associations of inhalable grain dust exposure with respiratory health outcomes, rhinitis, and eczema reported by workers from rice, wheat, and maize storage facilities.
Methods:
A cross-sectional study of 136 workers (73 operators and 63 administrative staff and other workers) from eight Costa Rican grain storage facilities was conducted in 2014-2015. Full-shift personal inhalable dust samples from all workers were collected. Study participants were administered a short version of the European Community Respiratory Health Survey questionnaire to identify symptoms of asthma, chronic bronchitis, rhinitis, and eczema. Associations between grain dust exposure and health outcomes were assessed using multivariable logistic and negative binomial regression models adjusted for age, smoking history, grain type, and presence of pets or farm animals in the home.
Results:
The median inhalable grain dust concentration was 2.0 (25th to 75th percentile: 0.3-7.0) mg m-3. Higher concentrations of inhalable dust were associated with increased odds of (i) asthma symptoms or medication use [adjusted Odds ratio (ORa) per 10-fold increase in dust concentration 2.7; 95% confidence interval (CI): 1.3-6.7]; (ii) a score of at least two out of five symptoms suggestive of asthma (ORa 1.2; 95% CI: 1.0-1.3); and (iii) eczema (ORa 3.6; 95% CI: 1.7-9.6). No associations of inhalable grain dust exposure with chronic bronchitis and rhinitis were observed.
Conclusions:
High exposure to inhalable dust in Costa Rican grain storage facilities was associated to asthma symptoms and eczema in workers.
... Positive serological tests are associated with a high probability of reaction to food challenge [22]. However, this is not the case for the prediction of late eczematous reactions, which shows a positive predictive value of food-specific IgE of only 33% [55]. ...
The presentation of newborns (0 to 28 days), infants, and toddlers (28 days to 2 years) with eczematous skin lesions is always a diagnostic and therapeutic challenge. Although these lesions represent most commonly an early atopic dermatitis (AD), various other eczematous skin diseases must be ruled out. These differential diagnoses of early AD include immunodeficiency disorders. Ascertaining a diagnosis of early AD is difficult, because the clinical phenotype is extremely heterogeneous and pruritus, the hallmark of AD, is difficult to recognize at this early age. Most sets of diagnostic criteria for atopic dermatitis are not applicable in this very early age of life. Thus, the definitive diagnosis of early AD is challenging and may better be delayed with a preliminary diagnosis of indetermined “eczema infantum.” Once the clinical characteristics become evident in the further course of the disease and the chronically recurring course can be assessed, a diagnosis of early AD may be made.
... Mixed disorders typically manifest in the gastrointestinal (GI) tract and the skin. The relationship between food allergies and atopic dermatitis has been reviewed comprehensively elsewhere [32][33][34][35][36][37] . This review will address mixed food allergic GI disorders. ...
The prevalence of food allergies has been on the increase over the last 2 decades. Diagnosing food allergies can be complicated, as there are multiple types that have distinct clinical and immunologic features. Food allergies are broadly classified into immunoglobulin E (IgE)-mediated, non-IgE mediated, or mixed food allergic reactions. This review focuses on the clinical manifestations of the different categories of food allergies and the different tests available to guide the clinician toward an accurate diagnosis.
... Although food as a factors for AD have long been subject of debate, but now it is generally accepted that food allergens are important factors of AD particularly in children (73)(74)(75). AD and food allergy commonly co-exist with severe and persistent AD, particularly in those with early onset (76). Both ingestion of food as well as epicutaneous food application are capable of inducing eczematous skin lesions. ...
Atopic dermatitis is a chronic inflammatory skin condition including severe pruritus, xerosis, visible eczematous skin lesions that mainly begin early in life. Atopic dermatitis exerts a profound impact on the quality of life of patients and their families. The estimated lifetime prevalence of atopic dermatitis has increased 2~3 fold during over the past 30 years, especially in urban areas in industrialized countries, emphasizing the importance of life-style and environment in the pathogenesis of atopic diseases. While the interplay of individual genetic predisposition and environmental factors contribute to the development of atopic dermatitis, the recent increase in the prevalence of atopic dermatitis might be attributed to increased exposure to various environmental factors rather than alterations in human genome. In recent decades, there has been an increasing exposure to chemicals from a variety of sources. In this study, the effects of various environmental chemicals we face in everyday life - air pollutants, contact allergens and skin irritants, ingredients in cosmetics and personal care products, and food additives - on the prevalence and severity of atopic dermatitis are reviewed.
... 4 Filaggrin gene defects are an important precursor, which may increase the risk of allergic sensitisation. 5,6 It is this group of children with moderate-to-severe atopic eczema/dermatitis in whom underlying allergy to foods (e.g. cow's milk and hen's eggs) and/or inhalant aero-allergens (e.g. ...
We sought to determine the primary care-based prevalence of moderate-to-severe atopic eczema/dermatitis in children and to estimate what proportion had co-morbid aero-allergy and/or food allergy that was contributing to their atopic eczema/dermatitis.
Multi-centre, cross-sectional study.
Infants, children and young people aged between 0-17 years.
Primary Care.
General practice electronic health records were interrogated to identify children (0-17 years) with current moderate-to-severe atopic eczema/dermatitis. Eligible children were assessed by an allergy specialist nurse, this involving a detailed allergy history, examination and, if appropriate, measurement of total IgE and specific IgE to relevant aero-allergens and/or food allergens.
Prevalence of atopic eczema, moderate to severe atopic eczema, IgE-mediated atopic eczema.
We recruited eight practices, which together enrolled 16,877 children. Of these, 4331 (25.7%; 95% CI 25.0, 26.3) children had a recorded diagnosis of atopic eczema/dermatitis and 1316 (7.8%; 95% CI 7.4, 8.2) had treatment indicative of current moderate-to-severe atopic eczema/dermatitis. We recruited 159 children for clinical assessment, and complete data were available for 157. The clinical assessment revealed that 130/157 (82.8%) had no indication of IgE-mediated allergy contributing to their atopic eczema/dermatitis; the remaining 27/157 (17.2%; 95% CI 12.1, 23.9) were on clinical assessment considered to possibly have underlying IgE-mediated disease. Specific IgE tests were positive in 14/27 (51.9%; 95% CI 34.0, 69.3) children. Of the 14 children who tested positive, six (42.9%; 95% CI 21.4, 67.4) were positive to food allergens and six (42.9%; 95% CI 21.4, 67.4) to aero-allergens; the remaining two (14.3%; 95% CI 4.0, 40.0) were positive to both food and aero-allergens.
Although atopic eczema/dermatitis is a very common diagnosis in children in primary care, most appear to be relatively mild and/or transient. Only a small proportion of children had evidence of ongoing underlying IgE-mediated atopic eczema/dermatitis.
© The Royal Society of Medicine.
... These findings support the previous report that the presence of egg-specific IgE antibodies constitutes the earliest marker of atopy [21]. Filaggrin gene defects are strongly associated with atopic eczema [27]. Furthermore, the increased skin permeability may increase the risk of sensitization to food and other allergens, and the risk of developing atopic diseases [28]. ...
Objectives
A correct interpretation of sensitization to common allergens is critical in determining susceptibility to allergic diseases. The aim of this study was to investigate the patterns of sensitization to food and inhalant allergens, and their relation to the development of atopic diseases in early childhood.
Methods
Children aged 0 through 4 years from a birth cohort in the Prediction of Allergies in Taiwanese Children (PATCH) study were enrolled. Specific IgE antibody against food and inhalant allergens were measured and their association between total serum IgE levels and atopic diseases were assessed.
Results
A total of 182 children were regular followed up at clinics for a four-year follow-up period. The prevalence of food allergen sensitization increased markedly after 6 months of age, reaching up to 47% at 1.5 years of age and then declined significantly to 10% in parallel with a considerable increase in the prevalence of sensitization to inhalant allergens up to 25% at age 4. Food allergen sensitization appeared to be mainly associated with the elevation of serum total IgE levels before age 2. A combined sensitization to food and inhalant allergens had an additive effect on serum IgE levels after age 2, and was significantly associated with the risk of developing atopic diseases at age 4.
Conclusions
Sensitization to food occurs early in life, in parallel with the rising prevalence of sensitization to inhalant allergens at older age. A combined sensitization to food and inhalant allergens not only has an additive increase in serum IgE antibody production but also increases the risk of developing allergic respiratory diseases in early childhood.
... Nie jest przy tym jasne, które z wymienionych zjawisk są przyczynami, a które skutkami choroby. Na przykład rola sprawcza IgE-zależnej alergii pokarmowej w AE wydaje się przeceniana i w rzeczywistości alergia pokarmowa może być zjawiskiem wtórnym do wyprysku [60, 62, 142, 163] . Samo wprowadzenie terminu " atopowe zapalenie skóry " było krytykowane jako " nieszczęśliwy wybór " już w 1975 roku przez Georga Rajkę; twórca kryteriów diagnostycznych atopowego zapalenia skóry podkreślał, że wielu chorych na tę jednostkę w istocie nie wykazuje cech atopii [109], na co zwracają uwagę również współcześni badacze [47]. ...
The term "eczema" does not refer to a specific disease, but to a syndrome of characteristic clinical features that are common for a heterogeneous group of diseases with various etiology. The difficulty with differentiating various types of eczema is partly due to overlapping, sometimes even conflicting definitions. As the diagnosis is based mainly on clinical picture and history, diagnostic decisions are greatly influenced by beliefs of individual doctors. The aim of the present study was to discuss diverse types of eczema in the light of current knowledge, as well as propose a classification of eczema that could be useful for practical doctors. The proposed etiology-based classification comprises eczema types most relevant in the practice: eczema without identifiable exogenous triggers ("endogenous" atopic eczema), eczema caused by exogenous factors without involvement of specific hypersensitivity reactions (irritant contact dermatitis, microtrauma or friction dermatitis, phototoxic dermatitis and radiation dermatitis), eczema caused by exogenous factors with the involvement of specific hypersensitivity ("exogenous" atopic eczema, allergic contact dermatitis, photoallergic dermatitis, protein contact dermatitis), eczema due to autoimmune reactions (autoimmune eczema, autoimmune progesterone dermatitis), and finally, eczema due to impaired skin homeostasis (seborrhoeic dermatitis, asteatotic dermatitis, stasis dermatitis). Other, not included in this classification terms pertaining eczema are also discussed. In routine usage, sometimes it seems practical to use collective terms combining diseases with different etiology, yet sharing relevant clinical characteristics or legal status, such as nummular eczema, dishydrotic eczema, airborne dermatitis, hand eczema, foot eczema, consort/connubial dermatitis or occupational dermatitis. Key words: eczema, dermatitis, clinical entities, classification.
... The development of allergic disease in different organs often occurs together in the same person. Numerous studies have found positive associations between allergic rhinitis, asthma, atopic dermatitis, allergic conjunctivitis, and food allergies [4][5][6][7][8][9][10][11][12]. Irritable bowel syndrome (IBS) is also associated with allergy/atopy [9,[13][14][15]. ...
Parasympathetic nerves control the symptoms and inflammation of allergic diseases primarily by signaling through peripheral muscarinic receptors. Parasympathetic signaling targets classic effector tissues such as airway smooth muscle and secretory glands and mediates acute symptoms of allergic disease such as airway narrowing and increased mucus secretion. In addition, parasympathetic signaling modulates inflammatory cells and non-neuronal resident cell types such as fibroblasts and smooth muscle contributing to chronic allergic inflammation and tissue remodeling. Importantly, muscarinic antagonists are experiencing a rebirth for the treatment of asthma and may be useful for treating other allergic diseases.
... They commonly co-exist with severe and persistent AD, particularly in those with early onset. 62 FA is emerging as a major clinical and public health problem worldwide. It affects approximately 5-8% of children -with greatest prevalence in the first few years of life and gradual decrease during the first decade as tolerance develops -and 1-5% of adults. ...
Atopic dermatitis (AD) is a common, chronic or chronically relapsing, multifactorial skin disease that mainly occurs in children but affects also adults. AD usually begins early in life and often concerns people with a personal or family history of asthma and allergic rhinitis. AD is characterized by eczematous changes in the epidermis and originates from a late, T-cell mediated reaction associated to the formation and production of memory T-cell of TH2 type, occurrence of homing receptor at skin level and cutaneous lymphocyte-associated (CLA) antigens. Extrinsic or allergic AD, but not intrinsic AD, shows high total serum IgE levels and the presence of specific IgE for environmental and food allergens. A pivotal role in the pathogenesis of AD is played by filaggrin, a protein contained in the granular layer of the epidermis regulating the aggregation of keratin filaments. Mutation in the filaggrin gene causes decreased barrier function of the corny layers of the epidermis. This favours the enter through the skin of environmental allergens, especially the house dust mite, that further facilitates such entering by the proteolytic activity of its major allergen Der p 1. In fact, recent advances suggest that the dust mite, more than foods, is the major cause of allergic AD. As far as the causal diagnosis of AD is concerned, there is notable evidence supporting the capacity of the atopy patch test (APT) to reproduce the pathophysiologic events of AD. This makes APT a valuable diagnostic tool for AD.
... The prevalence of PN and tree nut allergy in children aged <18 years is 2.1%. 41 The reasons for the rise in food allergy are unknown, but there are several hypotheses, including the ''hygiene hypothesis,'' 42 the overall allergy march, 43 and epigenetics. 42,44 -46 Although the precise mechanisms involved in the development of PNA have not been fully elucidated, several mechanisms involved in PNA have been identified in humans and in animal models. ...
Prevalence of asthma and allergy has increased over the past 2-3 decades in Westernized countries. Despite increased understanding of the pathogenesis of asthma and allergic diseases, control of severe asthma is still difficult. Asthma is also associated with a high prevalence of anxiety, particularly in adolescents. There is no effective treatment for food allergy. Food allergy is often associated with severe and recalcitrant eczema. Novel approaches for treatment of asthma and food allergy and comorbid conditions are urgently needed. Traditional Chinese medicine, used in Asia for centuries, is beginning to play a role in Western healthcare. There is increasing scientific evidence supporting the use of traditional Chinese medicine for asthma treatment. Since 2005, several controlled clinical studies of "antiasthma" herbal remedies have been published. Among the herbal medicines, antiasthma herbal medicine intervention is the only antiasthma traditional Chinese medicine product that is a Food and Drug Administration investigational new drug that has entered clinical trials in the United States. Research into the effects and mechanisms of action of antiasthma herbal medicine intervention in animal models is actively being pursued. Research on traditional Chinese medicine herbal medicines for treating food allergy is rare. The herbal intervention Food Allergy Herbal Formula-2 is the only Food and Drug Administration botanical investigational new drug under investigation as a multiple food allergy therapy. This review article discusses promising traditional Chinese medicine interventions for asthma, food allergy, and comorbid conditions, and explores their possible mechanisms of action.
... Interestingly, no statistically significant association was found between AD and PFCs. A possible explanation was that various stronger risk factors, such as foodand aero-allergens, may contribute to AD than pre-natal PFC exposure (Wang et al., 2007;Worth and Sheikh, 2010). After adjusting for gender, gestational age, maternal age, maternal history of atopy, duration of breast feeding, and pre-natal ETS exposure, there was no significant association between AD and PFCs. ...
The role of perfluorinated compounds (PFCs) in the immune system and allergic diseases is not well-known. This study examined the effects of pre-natal exposure to PFCs on immunoglobulin E (IgE) levels and atopic dermatitis (AD).
In Taiwan Birth Panel cohort study, newborns with cord blood and peri-natal factors (i.e. birth body weight, weeks of gestation, and type of delivery) gathered at birth were evaluated. At the age of 2 years, information on the development of AD, environmental exposures, and serum total IgE were collected. The AD and non-AD children were compared for the concentration of cord blood serum PFCs measured by Ultra-performance liquid chromatography/triple-quadrupole mass (UPLC-MS/MS). Correlations among cord blood IgE, serum total IgE at 2 years of age, and cord blood PFC levels were made.
Of 244 children who completed the follow-up and specimen collections, 43 (17.6%) developed AD. Concentrations of cord blood serum perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS) were median (range) 1.71 (0.75-17.40), 5.50 (0.11-48.36), 2.30 (0.38-63.87), and 0.035 (0.035-0.420)ng/mL, respectively. PFOA and PFOS levels positively correlated with cord blood IgE levels (per ln-unit: β=0.134 KU/l, p=0.047 for PFOA; β=0.161 KU/l, p=0.017 for PFOS). Analyses stratified by gender revealed that PFOA and PFOS levels positively correlated with cord blood IgE levels only in boys (per ln-unit: β=0.206 KU/l, p=0.025 for PFOA; β=0.175 KU/l, p=0.053 for PFOS). When dividing cord blood serum PFCs into quartiles in the fully adjusted models, AD had no significant association with PFOS.
Pre-natal PFOA and PFOS exposures positively correlated with cord blood IgE levels.
Atopic eczema is a chronic, relapsing, inflammatory skin condition characterized by itch which affects 20–30% of schoolchildren and 5–10% of adults in the UK. The increased prevalence in both western industrialized countries and developing nations over the last 20 years highlights the strong role of environmental factors in mediating the disease. However, the identification of a strong association between atopic eczema and mutations in the gene encoding filaggrin in 2006 has provided a paradigm shift in our understanding of the role of genetics in this condition and the importance of the function of the epidermal barrier. Indeed, interventions to repair the epidermal barrier show promise in both the treatment and prevention of atopic eczema and its complications. T‐helper 2 cells are central to mediating atopic eczema inflammation and specific targeted interventions are progressing well in clinical trials. Further developments in our understanding of disease pathogenesis, including the role of thymic stromal lymphopoeitin, and recently discovered subsets of immunocytes, are exciting targets and provide an optimistic future for the management of this challenging disease. However, topical therapy with emollients, corticosteroids and calcineurin inhibitors remains the mainstay of treatment. Thus, for more severe disease, current therapeutic options remain limited. As a result, atopic eczema still contributes a significant quality of life and financial burden on society and health care systems worldwide.
Background:
Recent data have shown an increasing occurrence of atopic dermatitis (AD) in children and adolescents, as well as in adults. Most of the epidemiologic research on AD is limited to pediatric and youth populations and is based on self-reported questionnaires.
Methods:
A nationwide, population-based, cross-sectional retrospective study of adolescents with AD was performed to estimate its prevalence, trends, and association with demographic factors and comorbidities. The study included all Israeli teens going through medical evaluation as part of the assessment before being conscripted into the military from 1998 to 2013.
Results:
A total of 1,187,757 adolescents were included in the study population, with an overall prevalence of AD of 0.64% in boys and 0.9% in girls. Over the study period, the prevalence of AD steadily increased, especially in the mild disease group. A greater risk of AD was found in subjects with high predicted socioeconomic status (male: odds ratio [OR] 1.14 [95% confidence interval {CI} 1.11, 1.16]; female: OR 1.08, [95% CI 1.05, 1.10]) and Israeli-born subjects (male: OR 1.34 [95% CI 1.21, 1.48]; female: OR 1.12 [95% CI 1.01, 1.23]). Allergic conditions such as asthma, conjunctivitis, and contact dermatitis were more prevalent in subjects with AD. There was a significantly higher prevalence of migraine in patients with AD (male: OR 1.35 [95% CI 1.18, 1.54]; female: OR 1.51 [95% CI 1.30, 1.74]).
Conclusion:
This large cross-sectional study demonstrates the increasing prevalence of AD in adolescents and its relation to other allergic diseases and migraine. It is hoped that greater awareness of the distinctive epidemiologic characteristics of this population will lead to better recognition and management of the disease and its comorbidities.
La dermatite atopica (DA) o eczema atopico è una malattia infiammatoria cutanea che interessa prevalentemente i bambini, ma è ben rappresentata in età adulta e, a causa delle caratteristiche cliniche e del tipico andamento cronico recidivante, influisce notevolmente sulla qualità della vita dei pazienti e dei loro familiari (Lipozencic e Wolf, 2007).
Food allergy is a growing problem in modern society that deserves an ongoing effort to develop safe and effective treatment. Traditional Chinese medicine (TCM) has a long human use history and is beginning to play a role in health care in the US, mainly via licensed practitioners. There is also increasing scientific evidence demonstrating the safety and efficacy of TCM for allergic diseases. We developed a herbal formula named food allergy herbal formula-2 (FAHF-2) derived from a classical herbal formula Wu-Mei-Wan that has been used in TCM to treat intestinal parasite infections and food allergy-like symptoms. Over the past years, we have generated a number of publications showing that FAHF-2 can prevent and reverse established peanut allergies in an animal model of peanut anaphylaxis, and that the effect is long lasting. These studies suggest that FAHF-2, and perhaps other Chinese herbal medicines, may have a potential for treating food allergies. FAHF-2 is the first botanical drug that has entered clinical trials as a United States Food and Drug Administration Investigational New Drug. Our phase I studies showed that FAHF-2 is safe and well-tolerated. Food allergies are often associated with other allergic conditions such as eczema (atopic dermatitis), particularly recalcitrant eczema. Given the growing interest in alternative and complementary medicine (CAM) therapies from both families and physicians, we have established a TCM/integrative medicine clinical program to help children and adults with recalcitrant eczema associated with food allergies. The clinical outcomes have been well received. TCM treatment improved quality of life, reduced food (including peanut) specific IgE levels, can be used long term, and no side effects were observed. TCM as monotherapy or integrative medicine may be an important approach for treating food allergies and associated eczema. It is possible that some of these herbal remedies will progress from dietary supplements to prescription drugs via clinical studies.
Purpose of review:
We conducted a systematic literature search for studies investigating the link between atopic dermatitis and food sensitization or clinically significant allergy (FA) in adults, to assess the strength of the association between the two diseases in both general and selected populations.
Recent findings:
Around 10% of adults with FA have concomitant atopic dermatitis at the population level. Adult atopic dermatitis patients show much higher rates of sensitization to foods than healthy individuals, in particular to food proteins cross-reactive with airborne allergens, rather than the food allergens that typically predominate amongst children with atopic dermatitis. When food challenges have been performed, rather than relying on questionnaire information and specific IgE testing alone, they often do not confirm eczematous reactions. Only half of patients who have challenge-proven FA improve on a strict elimination diet.
Summary:
Challenge-proven FA in adults with atopic dermatitis is uncommon. The incidence of new-onset FA in adult atopic dermatitis patients is currently unknown, as are the main routes of sensitization. There is increasing evidence from studies in infants that sensitization to food protein can occur across the skin barrier, in particular in the presence of eczematous skin inflammation. Carefully conducted large longitudinal studies amongst adults that take into account skin barrier function and genetics are required.
Nitrogen dioxide (NO2), a surrogate measure of traffic-related air pollution (TRAP), has been associated with incident childhood asthma. Timing of exposure and atopic status may be important effect modifiers. We collected cross-sectional data on asthma outcomes from Toronto school children aged 5-9years in 2006. Lifetime home, school and daycare addresses were obtained to derive birth and cumulative NO2 exposures for a nested case-control subset of 1497 children. Presence of other allergic disease (a proxy for atopy) was defined as self-report of one or more of doctor-diagnosed rhinitis, eczema, or food allergy. Generalized estimating equations were used to adjust for potential confounders, and examine hypothesized effect modifiers while accounting for clustering by school. In children with other allergic disease, birth, cumulative and 2006 NO2 were associated with lifetime asthma (OR 1.46, 95% CI 1.08-1.98; 1.37, 95% CI 1.00-1.86; and 1.60, 95% CI 1.09-2.36 respectively per interquartile range increase) and wheeze (OR 1.44, 95% CI 1.10-1.89; 1.31, 95% CI 1.02-1.67; and 1.60, 95% CI 1.16-2.21). No or weaker effects were seen in those without allergic disease, and effect modification was amplified when a more restrictive algorithm was used to define other allergic disease (at least 2 of doctor diagnosed allergic rhinitis, eczema or food allergy). The effects of modest NO2 levels on childhood asthma were modified by the presence of other allergic disease, suggesting a probable role for allergic sensitization in the pathogenesis of TRAP initiated asthma.
Food allergies are increasing in the pediatric population. A review of the literature suggests that clinicians may lack knowledge about food allergy. Avoidance is currently the standard of care. As a result, managing these children and families is difficult. Clinicians must be knowledgeable in order to educate their patients. This article provides information for the pediatric provider concerning prevalence in children, pathophysiology, comorbidities, history and physical examination, diagnostic testing and referral, and educational and preventative strategies.
The evaluation of soy allergy in patients over 14 years of age suffering from atopic dermatitis. The evaluation of the correlation to the occurence of peanut and pollen allergy.
Altogether 175 persons suffering from atopic dermatitis were included in the study: Specific IgE, skin prick tests, atopy patch tests to soy, history and food allergy to peanut and pollen allergy were evaluated.
The early allergic reaction to soy was recorded in 2.8% patients. Sensitization to soy was found in another 27.2% patients with no clinical manifestation after soy ingestion. The correlation between the positive results of examinations to soy and between the occurence of peanut and pollen allergy was confirmed in statistics.
Almost one third of patients suffering from atopic dermatitis are sensitized to soy without clinical symptoms. The early allergic reaction to soy occur in minority of patients suffering from atopic dermatitis.
La dermatite atopique est souvent la première étape de la marche atopique conduisant à l’asthme. L’asthme succédant à la dermatite atopique sera d’autant plus fréquent et plus sévère que les manifestations cutanées seront sévères et associées à une polysensibilisation IgE dépendante. Les déficits en filaggrine renforcent cette tendance, surtout en cas d’allergie alimentaire. Il est indispensable de traiter la peau mais il n’est pas certain que cela suffise à prévenir la survenue d’asthme et/ou de rhinite allergiques.
Atopic dermatitis (AD) is a chronic inflammatory skin disease with a large impact on quality of life of the patients and their families. In most cases, the diagnosis of AD can easily be made based on (family) history and clinical examination. If necessary, a practical set of diagnostic criteria such as the UK diagnostic criteria can be used. During the diagnostic phase, it is important to pay attention to atopic comorbidity, such as allergic airway disease (allergic asthma and/or rhinitis), allergic eye disease (atopic (kerato) conjunctivitis) and immediate-type food allergy. This will not have direct consequences for the treatment of AD, but may be important for the overall well-being of the patient. Psychological factors, such as family circumstances, work/school performance and lifestyle factors should also be explored. Severity scoring using properly validated scoring lists may not be necessary for the diagnosis, however, is recommended for monitoring therapy. Simple scoring systems, such as TIS and IGA are easy to perform in daily practice. Several flare factors in AD, such as exposure to irritants or UV light, can be identified by history and clinical examination: in individual cases, additional diagnostic tests may sometimes be useful to confirm clinical suspicion. There is only limited evidence that allergen exposure to aeroallergens and/or food allergens influences AD severity. Therefore, routine allergen testing is not necessary for diagnosis and treatment of AD. The decision to perform allergen tests mainly depends on atopic comorbidity.
Few studies concerning the occurrence of cow's milk allergy with the use of double-blind, placebo controlled food challenge test in adolescents and adult patients suffering from atopic dermatitis exist.
To evaluate the occurrence of cow's milk allergy in adolescents and adults suffering from atopic dermatitis.
Altogether 179 persons suffering from atopic dermatitis were included in the study: 51 men and 128 women entered the study with the average age of 26.2 (s.d. 9.5 years). Complete dermatological and allergological examinations were performed.
The positive results in specific IgE and in skin prick tests were recorded in 12% of patients. According to the open exposure tests and double-blind, placebo controlled food challenge tests these patients are only sensitized to cow's milk without clinical symptoms of allergy. Double-blind, placebo controlled food challenge test confirmed food allergy to cow milk only in one patient (worsening of atopic dermatitis), the oral allergy syndrome was observed in another one patient, occurrence of this allergy was altogether 1.1%.
Cow's milk allergy rarely plays a role in the worsening of atopic dermatitis in adolescent and adult patients.
To evaluate the effect of a diagnostic hypoallergenic diet on the severity of atopic dermatitis in patients over 14 years of age.
The diagnostic hypoallergenic diet was recommended to patients suffering from atopic dermatitis for a period of 3 weeks. The severity of atopic dermatitis was evaluated at the beginning and at the end of this diet (SCORAD I, SCORAD II) and the difference in the SCORAD over this period was statistically evaluated.
One hundred and forty-nine patients suffering from atopic dermatitis were included in the study: 108 women and 41 men. The average age of the subjects was 26.03 (SD: 9.6 years), with the ages ranging from a minimum of 14 years to a maximum of 63 years. The mean SCORAD at the beginning of the study (SCORAD I) was 32.9 points (SD: 14.1) and the mean SCORAD at the end of the diet (SCORAD II) was 25.2 points (SD: 9.99). The difference between SCORAD I and SCORAD II was evaluated with the Wilcoxon signed-rank test. The average decrease of SCORAD was 7.7 points, which was statistically significant (P=.00000).
Introduction of the diagnostic hypoallergenic diet may serve as a temporary medical solution" in patients suffering from moderate or severe forms of atopic dermatitis. It is recommended that this diet be used in the diagnostic workup of food allergy.
Atopic dermatitis is a chronic allergic inflammatory disease of the skin. Its pathophysiology involves an orchestrated sequence of allergic provocation by IgE-mediated and non-IgE-mediated Th2 responses to allergens. Allergen sensitization precedes the immunopathogenesis. Th2 cytokines such as IL-4 and IL-5 play a key role in both the sensitization and effector phases of allergic skin inflammation. Recently, the roles of new cytokines including IL-16, IL-17, IL-21, IL-22, IL-23, IL-27, IL-31, IL-33, IL-35 and thymus stromal lymphopoietin (TSLP), and Th2 polarization in the immunopathogenesis of skin inflammation and physically injured skin have been described, in addition to roles for IL-4, IL- 5, IL-9, IL-13, IFN-γ and TGF-β. Sensitization occurs via the skin for aeroallergen including house dust mites and superantigens and through the gastrointestinal tract for food allergens. Alternatively, food allergens can be sensitized through skin. Atopic dermatitis is described under the structure of sensitization phase and effector phase in this review. Especially, the clinically effective applications of cytokines in AD and relevant patents are updated in this review.
This review summarizes studies discussing temporal trends in the prevalence of food allergy as well as potential factors associated with the development of food allergy. In addition, we will address the potential hypotheses accounting for the apparent increase in food allergy prevalence. Studies suggest increased prevalence of food allergy. However, relatively little is known about its pathogenesis. This review aims to assess temporal trends in the prevalence of food allergy and discuss potential genetic, environmental, and demographic determinants. The search strategy examined the medical literature database MEDLINE (using PubMed) for the time period of January 1, 2002 to January 31, 2012. In recent decades, the prevalence of food allergy in general has increased by 0.60 % [95 % confidence interval (CI), 0.59 %-0.61 %] and the prevalence of peanut allergy by 0.027 % (95 % CI, 0.026 %-0.028 %), but it has now likely stabilized in developed countries. Genes, the environment, and demographic characteristics play a role in the pathogenesis of food allergy. Numerous environmental and demographic factors as well as gene-environment interactions may account for this increase in prevalence, but further studies are required to tease out their relative contribution.
The complex relationship between food allergy and infantile eczema has prompted divergent approaches to investigating potential food triggers in eczematous patients. It is well recognised that a significant proportion of infants with eczema have immunoglobulin E-mediated food allergy, reported to range between 20-80%. Determining whether certain foods trigger an eczematous flare in individual infants with eczema is difficult. For all infants with eczema, good skin care is the mainstay of treatment but identifying and avoiding triggers (both allergic and non-allergic) is important in some infants. Given this, we have a developed an algorithm that can be used by dermatologists in the investigation and management of food allergies in infantile eczema. Issues such as patient selection, investigation and elimination diets are addressed, with reference to relevant evidence in the literature. Our aim is to provide dermatologists with a framework to manage food allergies in infantile eczema, allowing the problem to be addressed with confidence.
The aim of this paper was to investigate the association between birthweight and prevalence of food allergies using a national sample of US children. Adult report of birthweight and child food allergies were obtained for years 2005-2009 from the National Health Interview Survey (NHIS), a cross-sectional household survey of the US population. A total of 51,748 children aged 0-17 years were included in the analyses representing over 73 million children. Multivariable logistic regression analyses examined associations between birthweight categories and food allergies stratified by age and gender; accounting for the complex design of NHIS. Children aged 6-12 years who were born very low birthweight (500-1,499 g) were more likely to have reported food allergy compared to referent (3,000-3,499 g), OR = 1.72; 95% CI: 1.02-2.91. However, there was no clear trend of an association between birthweight and food allergy with increasing or decreasing birthweight across all ages. Estimates were generally stronger in younger male children as compared to estimates in females of the same age group. Marginal associations for respiratory allergy (OR = 1.52; 95% CI: 1.02-2.29) and hay fever (OR = 1.54; 95% CI: 0.93-2.54) were observed among very low birthweight children aged 0-5 years. There was limited evidence for a clear association between birthweight and food allergy. Marginal associations observed in children weighing 500-1,499 g at birth support efforts to minimize preterm births and very low birthweight given the increase in pediatric food allergies and the large number of children born low birthweight each year in the US.
While genetic factors are known to be important in the development of sensitization to foods, it is not known whether they also play a role in clinical allergic reactivity to foods.
We aimed to determine whether parental atopic diseases are associated with a higher risk of a reaction to common allergenic foods when tested in a double-blind, placebo-controlled food challenge (DBPCFC).
Parents of children suspected of being food allergic were interviewed about their own and their child's atopic history. Specific IgE and skin prick tests to food allergens and the outcome of food challenges in the child were recorded.
Data from 553 double-blind food challenges performed in 396 children were analyzed. The foods tested were milk (n = 185), egg (n = 110), peanut (n = 198) and hazelnut (n = 60). Only parental eczema was significantly associated with positive outcomes for food challenges with milk after correction for age, sex, atopic comorbidity in the child and milk-specific IgE test results (odds ratio 3.1, 95% confidence interval 1.5-6.3).
Children with a positive DBPCFC to milk more frequently have parents with eczema than children with a negative test. This effect of parental eczema was not seen in children challenged with egg, peanut or hazelnut. Clinical reactivity to milk may be caused by genetic factors which are shared with parental eczema to a greater extent than clinical reactivity to other foods.
Allergy to peanuts is associated with considerable morbidity and, in a minority of cases, mortality. Natural resolution to peanut allergy occurs in only a few cases, hence the need to find effective interventions. Peanut oral immunotherapy (OIT) is a potentially important new therapeutic development.
To assess the benefits and harms of OIT for peanut allergy.
Fourteen databases were searched for published reports and unpublished/in-progress studies. We included studies employing randomised controlled trial (RCT), quasi-RCT, controlled clinical trial, controlled before-and-after, interrupted time series, and case series designs.
Six studies enrolling a total of 85 participants satisfied our inclusion criteria. All studies employed a case series design and were thus judged to be at high risk of bias. Overall, this body of evidence provided suggestive evidence that it is possible for many participants to increase their threshold dose for peanut exposure whilst receiving treatment. Adverse reactions were common and, whilst most of these were relatively minor, some were potentially life-threatening.
OIT appears to be a potentially promising new therapy for the short- to medium-term management of carefully selected and monitored patients with peanut allergy. The effectiveness and cost-effectiveness of OIT - particularly over the longer term - need to be clearly established using more robust designs before its clinical use can be contemplated. Given the risk of triggering serious adverse reactions, OIT should not be administered outside clinical trial settings.
The aim of this study was to evaluate the occurrence of egg allergy in patients over 14 years old suffering from atopic eczema and especially to evaluate if egg allergy can deteriorate the course of atopic eczema in this group of patients.
Altogether 179 patients suffering from atopic eczema were included in the study: 51 men and 128 women, with an average age of 26.2 years (SD 9.5 years), with median SCORAD 31.6 (SD 13.3) points. A complete allergological and dermatological examination was performed on all patients, including diagnostic work-up of food allergy to egg [skin prick tests, atopy patch tests (APTs), measurement of specific IgE level to egg yolks or whites]. Open exposure test (OET) with egg was performed in patients with positive results in some of these diagnostic methods. Food allergy to egg was determined according to positive results in the OET or according to sufficient anamnestical data about the severe allergic reaction after the ingestion of an egg.
An allergy to egg was confirmed in 11 patients out of 179 (6%). Of these patients, only six (3.3%) had a clear improvement in the SCORAD after the elimination of egg. Other triggering factors may cause exacerbation of the atopic eczema in the patients enrolled in the study. Twenty-eight percent of patients were only sensitized to egg without clinical symptoms. ATPs were a useful tool in the diagnosis of food allergy to egg in patients without IgE reactivity.
Egg allergy may play an important role in the worsening of atopic eczema acting as a triggering-exacerbating factor in a minority of patients. The diagnostic work-up may comprise the challenge tests to confirm the food allergy to egg.
To investigate whether filaggrin gene defects, present in up to one in 10 western Europeans and North Americans, increase the risk of developing allergic sensitisation and allergic disorders.
Systematic review and meta-analysis.
Medline, Embase, ISI Science Citation Index, BIOSIS, ISI Web of Knowledge, UK National Research Register, clinical trials.gov, the Index to Theses and Digital dissertations, and grey literature using OpenSIGLE.
Genetic epidemiological studies (family, case-control) of the association between filaggrin gene defects and allergic sensitisation or allergic disorders.
Atopic eczema or dermatitis, food allergy, asthma, allergic rhinitis, and anaphylaxis, along with relevant immunological variables relating to the risk of allergic sensitisation as assessed by either positive skin prick testing or increased levels of allergen specific IgE.
24 studies were included. The odds of developing allergic sensitisation was 1.91 (95% confidence interval 1.44 to 2.54) in the family studies and 1.57 (1.20 to 2.07) in the case-control studies. The odds of developing atopic eczema was 1.99 (1.72 to 2.31) in the family studies and 4.78 (3.31 to 6.92) in the case-control studies. Three studies investigated the association between filaggrin gene mutations and allergic rhinitis in people without atopic eczema: overall odds ratio 1.78 (1.16 to 2.73). The four studies that investigated the association between filaggrin gene mutations and allergic rhinitis in people with atopic eczema reported a significant association: pooled odds ratio from case-control studies 2.84 (2.08 to 3.88). An overall odds ratio for the association between filaggrin gene mutations and asthma in people with atopic eczema was 2.79 (1.77 to 4.41) in case-control studies and 2.30 (1.66 to 3.18) in family studies. None of the studies that investigated filaggrin gene mutations and asthma in people without atopic eczema reported a significant association; overall odds ratio was 1.30 (0.7 to 2.30) in the case-control studies. The funnel plots suggested that publication bias was unlikely to be an explanation for these findings. No studies investigated the association between filaggrin gene mutations and food allergy or anaphylaxis.
Filaggrin gene defects increase the risk of developing allergic sensitisation, atopic eczema, and allergic rhinitis. Evidence of the relation between filaggrin gene mutations and atopic eczema was strong, with people manifesting increased severity and persistence of disease. Filaggrin gene mutations also increased the risk of asthma in people with atopic eczema. Restoring skin barrier function in filaggrin deficient people in early life may help prevent the development of sensitisation and halt the development and progression of allergic disease.
Asthma prediction in early infancy is essential for the development of new preventive strategies. Loss-of-function mutations in the filaggrin gene (FLG) were identified as risk factors for eczema and associated asthma.
We evaluated the utility of the FLG mutations for the prediction of asthma.
Eight hundred seventy-one individuals of the prospective German Multicenter Allergy Study cohort were genotyped for 3 FLG mutations. Information on asthma, eczema, and food sensitization was available from birth to 13 years of age. Pulmonary function was measured from 7 to 13 years of age. The predictive value of the FLG mutations and of atopic phenotypes in infancy was assessed for asthma.
In infants with eczema and sensitization to food allergens, the FLG mutations predicted childhood asthma with a positive predictive value of 100% (95% CI, 65.5% to 100%). This subgroup was characterized by a significant decrease in pulmonary function until puberty and represented 8.1% of all asthmatic children and 19.1% of patients with asthma after infantile eczema. We found a strong synergistic interaction between the FLG-null alleles and early food sensitization in the disease transition from eczema to asthma (relative excess risk due to interaction, 2.64; 95% CI, 1.70-3.98; P = .00040).
FLG mutations and food sensitization represent 2 distinct mechanisms interacting in the pathogenesis of asthma. In infants with eczema and food sensitization, genotyping of the FLG mutations allows the prediction of asthma before the onset of symptoms. Our findings might facilitate the development of early subgroup-specific interventions to prevent the progression from eczema to asthma.
Atopic disease, including atopic dermatitis (eczema), allergy and asthma, has increased in frequency in recent decades and now affects approximately 20% of the population in the developed world. Twin and family studies have shown that predisposition to atopic disease is highly heritable. Although most genetic studies have focused on immunological mechanisms, a primary epithelial barrier defect has been anticipated. Filaggrin is a key protein that facilitates terminal differentiation of the epidermis and formation of the skin barrier. Here we show that two independent loss-of-function genetic variants (R510X and 2282del4) in the gene encoding filaggrin (FLG) are very strong predisposing factors for atopic dermatitis. These variants are carried by approximately 9% of people of European origin. These variants also show highly significant association with asthma occurring in the context of atopic dermatitis. This work establishes a key role for impaired skin barrier function in the development of atopic disease.
Background Studies of Australian infants have reported that more than 80% of those with moderate atopic eczema (AE) have high levels of IgE food sensitization (IgE-FS) that are commonly associated with IgE food allergy.
Objectives To explore the relationship between high levels of IgE-FS and AE in a large cohort of young children with eczema participating in a multi-centre, international study.
Methods Two thousand one hundred and eighty-four subjects (mean age 17.6 months, range 11.8–25.4; 1246 males) with active eczema from atopic families from 94 centres in 12 countries were studied. Clinical history, Scoring Atopic Dermatitis index as a measure of eczema severity and CAP-FEIA measurements for total IgE and IgE antibody levels to cow milk, egg and peanut were entered into a database. If CAP-FEIA levels exceeded previously reported age-specific cut-off levels for 95% positive predictive values (PPVs) for food allergy, subjects were defined as having high-risk IgE-FS (HR-IgE-FS).
Results Serum was available from 2048 patients; 55.5% were atopic. The frequency of HR-IgE-FS to milk, egg and/or peanut was the greatest in patients whose eczema developed in the first 3 months of life and the least in those whose eczema developed after 12 months (P<0.0001). In a regression analysis to allow for potential confounding factors, children with HR-IgE-FS had the most severe eczema and the youngest age of onset (P<0.001); 64% of infants with severe eczema of onset-age <3 months had HR-IgE-FS.
Conclusion Early-onset severe eczema in infancy was associated with HR-IgE-FS.
Clinical implications Food allergies should be routinely assessed in infants with moderate or severe eczema.
Capsule summary In eczematous infants, the earlier the age of onset, and the greater the severity of eczema, the greater the frequency of associated high levels of IgE-FS.
In this article we discuss 3 hypotheses to attempt to understand why preventive measures thus far studied with the aim of preventing (or delaying) the development of asthma have shown such disappointing results. The most likely explanation is that the development of a multifactorial disease, such as asthma, is extremely difficult, if not impossible, to prevent by eliminating only one risk factor. In a meta-analysis we investigated the effect of a multifaceted and monofaceted intervention in 10 prospective birth cohorts of a total of 3473 children on a diagnosis of asthma. Multifaceted intervention studies had an odds ratio (OR) of 0.73 (95% CI, 0.55-0.97), whereas the monointervention studies had an OR of 1.22 (95% CI, 0.83-1.78) in patients younger than 5 years and an OR of 0.52 (95% CI, 0.32-0.84) versus 0.93 (95% CI, 0.66-1.31) in patients older than 5 years. We therefore hypothesize that studies with a multifaceted approach will have a much greater chance of being successful than studies using a monofaceted approach, with the latter being unlikely to yield a clinically relevant reduction of asthma.
Peanut allergy has increased in frequency and severity such that it is now responsible for considerable morbidity and in some cases mortality. This has led to conflicting policies aimed at reducing the risk of children developing peanut allergy. Expectant women and parents of young children, as well and their clinicians, are therefore often unclear about whether to avoid peanuts.
We searched the Cochrane Library and PubMed using a combination of MeSH and free text terms from the inception of these databases to November 2009 to identify relevant systematic reviews and original studies that had investigated the effect of peanut avoidance in pregnancy, in mothers who were lactating, and in the diets of infants, on the risk of subsequently developing peanut allergy. We also searched Google Scholar and online trial registries (ClinicalTrials.gov and Controlled-trials.com) to identify unpublished and ongoing randomised controlled trials.
### Changing advice on the role of peanut avoidance
In 1998 the UK government advised that those at “high risk” of developing allergy (that is, those with a family history of allergic problems) may wish to avoid eating peanuts and products that contain peanuts during pregnancy, lactation, and weaning (until infant is aged 3 years).1 Similar advice was issued around the same time in several other countries.2 3
This advice on avoidance of peanuts was based on the findings of epidemiological studies, which suggested that exposure to peanuts during this “critical window” in early life may increase the risk of peanut allergy.4 5 Supportive, potentially more compelling, evidence came from the early randomised controlled …
This review summarizes clinically important findings from systematic reviews indexed in bibliographical databases between August 2007 and August 2008 that dealt with disease prevention (six reviews) and treatment of atopic eczema (seven reviews). Regarding disease prevention, two independent systematic reviews found some clinical trial evidence that ingestion of probiotics by mothers during pregnancy might reduce the incidence of subsequent eczema. Another review failed to find any clear benefit of prebiotics in eczema prevention. Although furry pets are often cited as causing allergic disease, a systematic review of observational studies found no evidence that exposure to cats or dogs at birth increases eczema risk. One very large review of studies of breastfeeding found some evidence of a protective effect on eczema risk, although all the studies were limited by their observational nature. A German group has attempted an overview of eczema prevention studies with a view to informing national guidelines. In terms of eczema treatment, two systematic reviews have confirmed the efficacy of topical tacrolimus ointment. Another review of 31 trials confirms the efficacy of topical pimecrolimus, although many of those trials were vehicle controlled, which limits their clinical utility. A review of 23 studies of desensitization therapy for allergic diseases found some evidence of benefit for eczema, which needs to be explored further. Despite the popularity of antistaphylococcal therapies for eczema, a Cochrane Review of 21 trials failed to show any clear benefit for any of the therapies for infected or clinically noninfected eczema. Another Cochrane Review dealt with dietary exclusions for people with eczema and found little evidence to support any dietary exclusion, apart from avoidance of eggs in infants with suspected egg allergy supported by evidence of sensitization. A review of 13 studies of probiotics for treating established eczema did not show convincing evidence of a clinically worthwhile benefit, an observation that has been substantiated in a subsequent Cochrane Review.
There is considerable international interest in understanding the sequential progression of multiple allergic conditions (also sometimes known as 'the allergic march').
To study the sequential progression of multiple allergic conditions in a national birth cohort throughout childhood.
We constructed a birth cohort of 43,477 children born in 1990 and registered in UK general practices within a year of birth, using the national General Practice Research Database. Of these, 24,112 with complete follow-up until the age of 18 years were studied in order to understand disease progression and to estimate the absolute and relative risks of developing second and third allergic diagnoses following an index allergic condition.
52.1% of children were diagnosed with at least one condition at some point in childhood. We were able to describe 15 different disease trajectories. Eczema was the most likely index condition with 60.7% [95% confidence interval (CI): 59.8-61.6] of allergy sufferers being diagnosed with this condition first. For those with a diagnosis of eczema, the relative risks of being diagnosed with asthma followed by rhinitis and rhinitis followed by asthma were 1.59 (95% CI: 1.32-1.91; P<0.0001) and 0.54 (95% CI: 0.43-0.68; P<0.0001), respectively. For those diagnosed with asthma first, the relative risks of being diagnosed with eczema followed by rhinitis and rhinitis followed by eczema were 1.27 (95% CI: 0.96-1.68; P=0.095) and 0.27 (95% CI: 0.20-0.36; P<0.0001), respectively. For those diagnosed with rhinitis first, the relative risks of being diagnosed with eczema followed by asthma and asthma followed by eczema were 0.64 (95% CI: 0.42-0.95; P=0.025) and 0.47 (95% CI: 0.32-0.67; P<0.0001), respectively.
Among children diagnosed with multiple allergic diseases there is likely to be a number of variants of 'the allergic march'. Of these, the diagnosis of eczema followed by asthma, which is in turn followed by rhinitis, is the most common trajectory. Surprisingly, some diagnoses indicate a possible strong protective effect of manifesting further likely allergic diagnoses.
The recent identification of loss-of-function mutations in the structural protein filaggrin as a widely replicated major risk factor for eczema sheds new light on disease mechanisms in eczema, a disease that had heretofore largely been considered to have a primarily immunologic etiopathogenesis. The filaggrin gene (FLG) mutation findings are consistent with a recently proposed unifying hypothesis that offers a mechanistic understanding of eczema pathogenesis synthesizing a heritable epithelial barrier defect and resultant diminished epidermal defense mechanisms to allergens and microbes, followed by polarized T(H)2 lymphocyte responses with resultant chronic inflammation, including autoimmune mechanisms. Although compelling evidence from genetic studies on FLG implicates perturbed barrier function as a key player in the pathogenesis of eczema in many patients, much is still unknown about the sequence of biologic, physicochemical, and aberrant regulatory events that constitute the transition from an inherited barrier defect to clinical manifestations of inflammatory eczematous lesions and susceptibility to related atopic disorders. The exact contribution of FLG to the wider atopic story, factors modifying FLG expression, and the role of other barrier proteins remain to be delineated. In this review we highlight recent advances in our understanding of the FLG genetics in the cause of eczema and related complex diseases.
Probiotics have been proposed as a treatment for eczema, but the results of intervention trials have been mixed.
To evaluate the efficacy of probiotics for treating eczema by performing a systematic review of randomized-controlled trials (RCTs).
We searched the Cochrane Skin Group Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PsycINFO, AMED, LILACS, ISI Web of Science, the reference lists of articles, ongoing clinical trial registers and conference proceedings. RCTs of live orally ingested microorganisms for the treatment of eczema were eligible for inclusion.
Twelve trials (781 participants) were identified. Meta-analysis of data from five of these trials showed that there was no significant reduction in eczema symptoms with probiotic treatment compared with placebo (mean difference -0.90 points on a 20-point visual analogue scale; 95% confidence interval -2.84, 1.04). Meta-analysis of data from seven trials showed no significant difference in investigator rated eczema severity between probiotic and placebo treatments. Subgroup analysis by eczema severity or presence of atopy did not identify a specific population in which probiotic treatment was effective. There was significant heterogeneity between studies; however, the results of three studies that used the same probiotic strain were concordant. The adverse events search identified case reports of sepsis and bowel ischaemia caused by probiotics.
Currently, probiotics cannot be recommended for treating eczema. The heterogeneity between studies may be attributable to probiotic strain-specific effects, which means that novel probiotic strains may still have a role in eczema management.
For many years, the advice to prevent food allergy was to postpone the introduction of allergens like egg, fish and peanut. However, elimination of food allergens during pregnancy and infancy failed to prevent food allergy. Instead, several studies indicate that early introduction of food like fish and peanuts may be beneficial. The most compelling illustration of this has been presented for peanuts. The prevalence of peanut allergy is lower in children in Israel than in the UK, despite introduction of peanut during infancy in Israel. Other studies have reported that early introduction of fish reduced the risk of allergic sensitization and allergic diseases like eczema.
Conclusion: Early introduction rather than avoidance may be a better strategy for the prevention of food allergy. The mechanism may be that early introduction of food allergens during infancy might induce tolerance, thereby preventing the development of allergy.
There remains a need to better characterize the epidemiology of allergic disorders, particularly in relation to describing the incidence, natural history and co-morbidity of allergic conditions.
To estimate the incidence and prevalence of clinician-diagnosed eczema, asthma and rhinitis, alone and in combination, in children and adolescents in the United Kingdom.
Using the national General Practice Research Database (GPRD) - one of the largest validated databases of routinely collected healthcare data in the world aggregating 3.6 million individuals - we constructed a retrospective birth cohort of 43,473 children born in the year 1990 and registered with a UK general practice within a year of birth. The cohort was followed until 2008 or the longest available follow-up period to determine the cumulative and age-specific incidence and prevalence rates of clinician-diagnosed eczema, asthma and rhinitis, and an 18-year prevalence of these conditions, alone and in combination.
Eczema had the highest incidence density of 226.9 per 10,000 person-years [95% confidence interval (CI): 225.8-228.0] followed by asthma [136.6;(95% CI: 135.7-137.5)] and rhinitis [61.4;(95% CI: 60.8-62.0)], by the age of 18 years. The incidence densities of suffering from one, two or all three allergic conditions were 323.2 (95% CI: 322.0-324.4), 206.4 (95% CI: 205.7-207.1) and 141.9 (95% CI: 141.4-142.4) per 10,000 person-years, respectively. Among the 24 112 children with a complete 18-year follow-up, eczema had the highest 18-year prevalence of clinician-diagnosed condition at 36.5% (95% CI: 35.9-37.2%) followed by asthma [22.9;(95% CI: 22.3-23.4%)] and rhinitis[11.4;(95% CI: 11.0-11.8%)]. The 18-year prevalence of more than one and all three conditions was 16.1% (95% CI: 15.6-16.6%) and 2.5% (95% CI: 2.4-2.8%), respectively.
This is one of the first studies to provide national estimates on the age-specific incidence and age-specific prevalence of the major allergic disorders showing clinician-diagnosed eczema, asthma and rhinitis to have high incidence rates in early childhood. A significant proportion of children experience and are diagnosed with multiple allergic conditions in early childhood.
The prevalence of eczema, particularly in younger children, increased substantially over the second half of the 20th century. Analysis of primary healthcare data-sets offers the possibility to advance understanding about the changing epidemiology of eczema.
To investigate recent trends in the recorded incidence, lifetime prevalence, prescribing and consulting behaviour of patients with eczema in England.
QRESEARCH is one of the world's largest national aggregated health databases containing the records of over nine million patients. We extracted data on all patients with a recorded diagnosis of eczema and calculated annual age-sex standardized incidence and lifetime period prevalence rates for each year from 2001-2005. We also analysed the consulting behaviour of these patients when compared with the rest of the QRESEARCH database population. The number of eczema prescriptions issued to people in England was also estimated.
The age-sex standardized incidence of eczema was 9.58 per 1000 person-years in 2001 and increased to 13.58 per 1000 patients in 2005 (p<0.001). By 2005, eczema affected an estimated 5,773,700 (95% confidence intervals [CI] 5,754,100-5,793,400) individuals in England, who, on average, consulted a general practitioner 4.02 (95% CI 4.01-4.03) times a year. During the study period, the number of eczema related prescriptions increased by 56.6% (95% CI 56.6-56.7), so by 2005 an estimated 13,690,300 (95% CI 13,643,200-13,737,600) prescriptions were issued.
Recorded incidence and lifetime prevalence of eczema in England continue to increase. Similar increases have also been observed in the estimated number of eczema prescriptions issued to the English population.
Peanut allergy is common, potentially severe and rarely resolves causing impaired quality of life. No disease-modifying treatment exists and there is therefore a need to develop a therapeutic intervention.
The aim of this study was to investigate whether peanut oral immunotherapy (OIT) can induce clinical tolerance to peanut protein.
Four peanut-allergic children underwent OIT. Preintervention oral challenges were performed to confirm clinical allergy and define the amount of protein required to cause a reaction (dose thresholds). OIT was then administered as daily doses of peanut flour increasing from 5 to 800 mg of protein with 2-weekly dose increases. After 6 further weeks of treatment, the oral challenge was repeated to define change in dose threshold and subjects continued daily treatment.
Preintervention challenges confirmed peanut allergy and revealed dose thresholds of 5-50 mg (1/40-1/4 of a whole peanut); one subject had anaphylaxis during challenge and required adrenaline injection. All subjects tolerated immunotherapy updosing to 800 mg protein and i.m. adrenaline was not required. Each subject tolerated at least 10 whole peanuts (approximately 2.38 g protein) in postintervention challenges, an increase in dose threshold of at least 48-, 49-, 55- and 478-fold for the four subjects.
We demonstrated a substantial increase in dose threshold after OIT in all subjects, including the subject with proven anaphylaxis. OIT was well tolerated and conferred protection against at least 10 peanuts, more than is likely to be encountered during accidental ingestion.
Atopic eczema is the most common inflammatory skin disease of childhood in developed countries. We performed a systematic review of randomized controlled trials to assess the effects of dietary exclusions for the treatment of established atopic eczema. Nine trials (421 participants) were included, most of which were poorly reported. Six were studies of egg and milk exclusion (n = 288), one was a study of few foods (n = 85) and two were studies of an elemental diet (n = 48). There appears to be no benefit of an egg- and milk-free diet in unselected participants with atopic eczema. There is also no evidence of benefit in the use of an elemental or few-foods diet in unselected cases of atopic eczema. There may be some benefit in using an egg-free diet in infants with suspected egg allergy who have positive specific IgE to eggs - one study found 51% of the children had a significant improvement in body surface area with the exclusion diet as compared with normal diet (95% CI 1.07-2.11) and change in surface area and severity score was significantly improved in the exclusion diet as compared with the normal diet at the end of 6 weeks (MD 5.50, 95% CI 0.19-10.81) and end of treatment (MD 6.10, 95% CI 0.06-12.14). Despite their frequent use, we find little good quality evidence to support the use of exclusion diets in atopic eczema.
The co-existence of allergic conditions, food allergy, eczema, allergic rhinitis, asthma and anaphylaxis is thought to be increasing. Analysis of primary healthcare data-sets offers the possibility to advance understanding about the changing epidemiology of multiple allergic disorders.
To investigate recent trends in the recorded incidence, lifetime prevalence and consulting behaviour of patients with multiple allergic disorders in England.
QRESEARCH is one of the world's largest national aggregated health databases containing the records of over nine million patients (including those who have left or died). Data were extracted on all patients with a recorded diagnosis of multiple allergic disorders, and annual age-sex standardized incidence and lifetime period prevalence rates were calculated for each year from 2001 to 2005. We also analysed the consulting behaviour of these patients when compared with the rest of the QRESEARCH database population.
The age-sex standardized incidence of multiple allergic disorders was 4.72 per 1000 person-years in 2001 and increased by 32.9% to 6.28 per 1000 patients in 2005 (p<0.001). Lifetime age-sex standardized prevalence of a recorded diagnosis of multiple allergic disorders increased by 48.9% from 31.00 per 1000 in 2001 to 46.16 in 2005 (p<0.001). Over this period, the mean consultation rate to general practitioners for these patients increased from 4.68 to 4.90 consultations per person per year.
Recorded incidence and lifetime prevalence of multiple allergic disorders in England have increased substantially in recent years.
Despite guidelines recommending avoidance of peanuts during infancy in the United Kingdom (UK), Australia, and, until recently, North America, peanut allergy (PA) continues to increase in these countries.
We sought to determine the prevalence of PA among Israeli and UK Jewish children and evaluate the relationship of PA to infant and maternal peanut consumption.
A clinically validated questionnaire determined the prevalence of PA among Jewish schoolchildren (5171 in the UK and 5615 in Israel). A second validated questionnaire assessed peanut consumption and weaning in Jewish infants (77 in the UK and 99 in Israel).
The prevalence of PA in the UK was 1.85%, and the prevalence in Israel was 0.17% (P < .001). Despite accounting for atopy, the adjusted risk ratio for PA between countries was 9.8 (95% CI, 3.1-30.5) in primary school children. Peanut is introduced earlier and is eaten more frequently and in larger quantities in Israel than in the UK. The median monthly consumption of peanut in Israeli infants aged 8 to 14 months is 7.1 g of peanut protein, and it is 0 g in the UK (P < .001). The median number of times peanut is eaten per month was 8 in Israel and 0 in the UK (P < .0001).
We demonstrate that Jewish children in the UK have a prevalence of PA that is 10-fold higher than that of Jewish children in Israel. This difference is not accounted for by differences in atopy, social class, genetic background, or peanut allergenicity. Israeli infants consume peanut in high quantities in the first year of life, whereas UK infants avoid peanuts. These findings raise the question of whether early introduction of peanut during infancy, rather than avoidance, will prevent the development of PA.
Recent insights into the relevance of the epidermal barrier function and its interaction with components of the innate and adaptive immune responses in patients with atopic dermatitis (AD) give rise to a number of novel potential treatment options. In particular, the identification of loss-of-function mutations in the barrier protein filaggrin and of a diminished expression of certain antimicrobial peptides in AD skin stimulates new concepts to think beyond the T(H)1/T(H)2 paradigm. This review will focus on these most recent discoveries and will discuss new and corresponding proof-of-concept trials in patients with AD. It will further speculate on novel ways to restore the homeostasis among the 3 major components in AD skin suspected to be clinically relevant.
Prior studies have suggested that heated egg might be tolerated by some children with egg allergy.
We sought to confirm tolerance of heated egg in a subset of children with egg allergy, to evaluate clinical and immunologic predictors of heated egg tolerance, to characterize immunologic changes associated with continued ingestion of heated egg, and to determine whether a diet incorporating heated egg is well tolerated.
Subjects with documented IgE-mediated egg allergy underwent physician-supervised oral food challenges to extensively heated egg (in the form of a muffin and a waffle), with tolerant subjects also undergoing regular egg challenges (in a form of scrambled egg or French toast). Heated egg-tolerant subjects incorporated heated egg into their diets. Skin prick test wheal diameters and egg white, ovalbumin, and ovomucoid IgE levels, as well as ovalbumin and ovomucoid IgG4 levels, were measured at baseline for all subjects and at 3, 6, and 12 months for those tolerant of heated egg.
Sixty-four of 117 subjects tolerated heated egg, 23 tolerated regular egg, and 27 reacted to heated egg. Heated egg-reactive subjects had larger skin test wheals and greater egg white-specific, ovalbumin-specific, and ovomucoid-specific IgE levels compared with heated egg- and egg-tolerant subjects. Continued ingestion of heated egg was associated with decreased skin test wheal diameters and ovalbumin-specific IgE levels and increased ovalbumin-specific and ovomucoid-specific IgG4 levels.
The majority of subjects with egg allergy were tolerant of heated egg. Continued ingestion of heated egg was well tolerated and associated with immunologic changes that paralleled the changes observed with the development of clinical tolerance to regular egg.
Atopic eczema (AE) is a chronic inflammatory skin disease characterized by pruritus, dry skin and an ongoing course of exacerbations and remissions. AE is a common disorder in children with a worldwide cumulative prevalence of 15-20% in this age group. AE has a strong familial predisposition. While AE is a complex disease with multiple gene involvement, recent interest has focused on genes involved in skin barrier/epidermal differentiation and in immune response/host defense. Recent developments and future directions on pathogenesis, diagnosis, natural course and prognosis are discussed.
There is much evidence that the development of allergic disorders may be related to early exposure of allergens, including those in breastmilk. We have tried to find out whether avoidance of food and inhaled allergens in infancy protects against the development of allergic disorders in high-risk infants. In a prenatally randomised, controlled study 120 infants with family history of atopy and high (greater than 0.5 kU/l) cord-blood concentrations of total IgE were allocated randomly to prophylactic and control groups. In the prophylactic group (n = 58), lactating mothers avoided allergenic foods (milk, egg, fish, and nuts) and avoided feeding their infants these foods and soya, wheat, and orange up to the age of 12 months; the infants' bedrooms and living rooms were treated with an acaricidal powder and foam every 3 months, and concentrations of Dermatophagoides pteronyssinus antigen(Der p l) in dust samples were measured by enzyme-linked immunosorbent assay. In the control group (n = 62), the diet of mothers and infants was unrestricted; no acaricidal treatment was done and Der p l concentrations were measured at birth and at 9 months. A paediatric allergy specialist unaware of group assignment examined the infants for allergic disorders at 10-12 months. Odds ratios were calculated by logistic regression analysis for various factors with control for other confounding variables. At 12 months, allergic disorders had developed in 25 (40%) control infants and in 8 (13%) of the prophylactic group (odds ratio 6.34, 95% confidence intervals 2.0-20.1). The prevalences at 12 months of asthma (4.13, 1.1-15.5) and eczema (3.6, 1.0-12.5) were also significantly greater in the control group. Parental smoking was a significant risk factor for total allergy at 12 months whether only one parent smoked (3.97, 1.2-13.6) or both parents smoked (4.72, 1.2-18.2).
Laboratory and clinical investigations over the past two decades have demonstrated that food allergy plays a pathogenic role in a subset of patients, primarily infants and children, with atopic dermatitis (AD). Approximately 40% of infants and young children with moderate to severe AD have food allergy, but identifying this subset of patients and isolating the relevant food allergens requires a high index of suspicion, the use of appropriate laboratory tests, and, in some cases, physician-supervised oral food challenges. Removal of the causal food protein(s) leads to clinical improvement but requires a great deal of education because most of the common causal foods (egg, milk, wheat, soy, peanut, and so forth) are ubiquitous in the food supply, and food elimination diets risk causing nutritional deficits. Fortunately, most food allergies resolve in early childhood, and food allergy is not a common cause for AD in older children and adults.
In many developed countries over one-fifth of the population are affected by one or more atopic allergic disorders. Several time-trend studies indicate that the prevalence and severity of eczema, rhinitis, and asthma is rapidly increasing1,2,3; and this observation, coupled with the widespread geographical variations in disease prevalence noted by the International Studies of Asthma and Allergies in Childhood, points to the strong contribution of environment to the aetiology4. However, the tendency of atopic allergic conditions to cluster both within individuals and within families suggests that genetic factors are also important.
Asthma is a condition characterized by reversible airflow obstruction and lower airway hyper-responsiveness, which results in episodic cough, wheeze and shortness of breath5. Inflammation of the nasal passages, manifesting as sneezing, nasal blockage and itchy rhinorrhoea, is the symptom complex known as rhinitis6. Eczema is the commonest cause of dermatitis in developed countries and affects approximately 20% of the general population7. The distribution of eczematous lesions varies with age, the face and trunk being most affected in infants whereas the flexor aspects of the limbs are typically affected in older children and adults. Advances in our understanding of the immunobiology of these disorders have shown them to have a common pathophysiological basis—an exaggerated and inappropriate IgE-mediated inflammation in response to allergen exposure—referred to as atopy8. The absence of objective and reliable criteria for defining either atopy or the atopic allergic conditions (eczema, rhinitis and asthma) has been and continues to be a major obstacle to establishing the genetic basis of atopic disorders.
This review is based in the main on articles retrieved by searching Medline, EMBASE and OMIM (Online Mendelian Inheritance in Man) electronic databases. Key websites of possible relevance were also searched9, including those of the British Society for Human Genetics10, the European Society for Human Genetics11, and the Human Mutation Database12. Allergy and genetic texts were consulted, and the analysis was helped by personal contacts with several experts on human genetics.
The prevalence of peanut allergy appears to have increased in recent decades. Other than a family history of peanut allergy and the presence of atopy, there are no known risk factors.
We used data from the Avon Longitudinal Study of Parents and Children, a geographically defined cohort study of 13,971 preschool children, to identify those with a convincing history of peanut allergy and the subgroup that reacted to a double-blind peanut challenge. We first prospectively collected data on the whole cohort and then collected detailed information retrospectively by interview from the parents of children with peanut reactions and of children from two groups of controls (a random sample from the cohort and a group of children whose mothers had a history of eczema and who had had eczema themselves in the first six months of life).
Forty-nine children had a history of peanut allergy; peanut allergy was confirmed by peanut challenge in 23 of 36 children tested. There was no evidence of prenatal sensitization from the maternal diet, and peanut-specific IgE was not detectable in the cord blood. Peanut allergy was independently associated with intake of soy milk or soy formula (odds ratio, 2.6; 95 percent confidence interval, 1.3 to 5.2), rash over joints and skin creases (odds ratio, 2.6; 95 percent confidence interval, 1.4 to 5.0), and oozing, crusted rash (odds ratio, 5.2; 95 percent confidence interval, 2.7 to 10.2). Analysis of interview data showed a significant independent relation of peanut allergy with the use of skin preparations containing peanut oil (odds ratio, 6.8; 95 percent confidence interval, 1.4 to 32.9).
Sensitization to peanut protein may occur in children through the application of peanut oil to inflamed skin. The association with soy protein could arise from cross-sensitization through common epitopes. Confirmation of these risk factors in future studies could lead to new strategies to prevent sensitization in infants who are at risk for subsequent peanut allergy.
Epidemiological studies indicate that the prevalence of allergic disorders such as allergic rhinitis, asthma, and eczema have increased during recent decades in many Western countries.1 Although anecdotal reports suggest that the prevalence of systemic allergic conditions may also be changing, only limited evidence exists to support this assertion.2 We report on trends in admissions for anaphylaxis, angio-oedema, food allergy, and urticaria, analysed by using national hospital discharge statistics from 1990-1 to 2000-1.
We obtained hospital admissions data from the hospital episode statistics system.3 This database records episodes of care after admission to hospital and assigns a primary diagnosis on discharge based on the international classification of diseases (ICD).4 Data are available by financial year (1 April-31 March). Diagnoses were classified using the ninth revision (ICD-9) up to March 1995 and using the tenth revision (ICD-10) thereafter. …
The nomenclature proposed in the October 2003 report of the Nomenclature Review Committee of the World Allergy Organization is an update of the European Academy of Allergology and Clinical Immunology Revised Nomenclature for Allergy Position Statement published in 2001. The nomenclature can be used independently of target organ or patient age group and is based on the mechanisms that initiate and mediate allergic reactions. It is assumed that as knowledge about basic causes and mechanisms improves, the nomenclature will need further review.
The "hygiene hypothesis" offers a potentially credible and parsimonious explanation for the increasing prevalence of allergy noted in many westernized populations. The authors review recent evidence both for and against this hypothesis.
A strong body of epidemiologic evidence indicates that the original observations, namely of a birth order effect and increased risk of atopic disorders in those born into small, affluent households, are robust findings. Improved hygiene is believed to mediate its effect through decreased exposure to infectious agents in early life, and recent evidence has focused attention on the importance of the gastrointestinal microbial environment. In particular, infection with hepatitis A, Helicobacter pylori, and toxoplasma in those living in temperate climates, and geoheminths in those living in endemic areas, have been shown to be associated with reduced risk of atopic manifestations. It is postulated that these infections exert their effect through critically altering T-helper (Th)1/Th2 regulation, which is supported by the examination of the cytokine profiles of cord mononuclear cells when exposed to gastrointestinal flora and, furthermore, emerging evidence on the benefits of probiotics on symptoms of atopic dermatitis. Attempts to identify an inverse relation between Th1- and Th2-mediated disorders (as might be predicted by the Th1/Th2 paradigm) have, however, yielded conflicting results, raising the possibility that this model may be something of an oversimplification.
The hygiene hypothesis remains a credible but nonspecific explanation for observed variations over time, place and persons at risk for developing atopic allergic disorders. More prospective studies are needed to unravel which infectious agents exert a protective effect and the time period of importance for sensitization. The clinical implications of these advances in our understanding of the etiology of atopic allergic disorders are currently limited.
The case of a 14-month-old boy with vitamin D deficiency rickets as a result of unsupervised dietary manipulation in the context of cow's milk allergy is presented. Adequate supervision by a qualified dietician, coupled with appropriate supplementation, is essential if nutritional compromise is to be avoided in children with food allergy.
Data for trends in prevalence of asthma, allergic rhinoconjunctivitis, and eczema over time are scarce. We repeated the International Study of Asthma and Allergies in Childhood (ISAAC) at least 5 years after Phase One, to examine changes in the prevalence of symptoms of these disorders.
For the ISAAC Phase Three study, between 2002 and 2003, we did a cross-sectional questionnaire survey of 193,404 children aged 6-7 years from 66 centres in 37 countries, and 304,679 children aged 13-14 years from 106 centres in 56 countries, chosen from a random sample of schools in a defined geographical area.
Phase Three was completed a mean of 7 years after Phase One. Most centres showed a change in prevalence of 1 or more SE for at least one disorder, with increases being twice as common as decreases, and increases being more common in the 6-7 year age-group than in the 13-14 year age-group, and at most levels of mean prevalence. An exception was asthma symptoms in the older age-group, in which decreases were more common at high prevalence. For both age-groups, more centres showed increases in all three disorders more often than showing decreases, but most centres had mixed changes.
The rise in prevalence of symptoms in many centres is concerning, but the absence of increases in prevalence of asthma symptoms for centres with existing high prevalence in the older age-group is reassuring. The divergent trends in prevalence of symptoms of allergic diseases form the basis for further research into the causes of such disorders.
Allergic disorders are common in the UK. This study reviews recent UK time trends in the prevalence, morbidity and mortality for allergic disorders, excluding asthma.
A trend analysis was performed over recent decades of national, representative or repeat surveys, primary care consultations, prescriptions, hospital admissions, and mortality.
Serial surveys showed that the prevalence of diagnosed allergic rhinitis and eczema in children have both trebled over the last three decades. While these long term trends were paralleled by the prevalence of disease symptoms, more recent symptom prevalence data suggest a decline. Similarly, GP consultation rates rose by 260% for hay fever and by 150% for eczema overall during the period 1971-91, but rates have stabilised over the past decade. Hospital admissions for eczema have been stable since 1995, and hospital admissions for allergic rhinitis have fallen to about 40% of their 1990 levels. Since 1990, admissions for anaphylaxis have increased by 700%, for food allergy by 500%, for urticaria by 100%, and for angio-oedema by 40%. Prescriptions issued for all types of allergy have increased since 1991.
The prevalence and healthcare usage for eczema and hay fever have increased substantially over recent decades, but may now be stabilising or even falling. In contrast, admissions for some systemic allergic diseases have risen sharply in the last decade which may indicate a rising incidence of these conditions. Although changes in treatment and other healthcare factors may have contributed to these trends, there may also be a change in the aetiology of allergic disease in the UK.
Early life allergen exposure may increase the risk of childhood allergy, but the protective effect of reduction in allergen exposure remains uncertain.
To evaluate the effect of reduction in food and house dust mite (HDM) allergen exposure in infancy in preventing asthma and allergy.
Infants, at higher risk because of family predisposition, were recruited prenatally and randomized to prophylactic (n = 58) and control (n = 62) groups. Prophylactic group infants were either breast-fed with mother on a low allergen diet or given an extensively hydrolyzed formula. Exposure to HDM was reduced by the use of an acaricide and mattress covers. The control group followed standard advice. Development of allergic diseases and sensitization to common allergens (atopy) was assessed blindly at ages 1, 2, 4, and 8 years in all 120 children.
Repeated measurement analysis, adjusted for all relevant confounding variables, confirmed a preventive effect on asthma: adjusted odds ratio (OR), 0.24; 95% CI, 0.09-0.66; P = .005; atopic dermatitis, OR, 0.23; CI, 0.08-0.64; P = .005; rhinitis, OR, 0.42; CI, 0.19-0.92; P = .03; and atopy, OR, 0.13; CI, 0.05-0.32; P < .001. The protective effect was primarily observed in the subgroup of children with persistent disease (symptoms at all visits) and in those with evidence of allergic sensitization.
Allergic diseases can be reduced, for at least the first 8 years of life, by combined food and HDM allergen avoidance in infancy.
Strict food and HDM allergen avoidance should be considered for prevention of allergy in high-risk infants.
Food allergy and atopic eczema (AE) may occur in the same patient. Besides typical immediate types of allergic reactions (i.e. noneczematous reactions) which are observed in patients suffering from AE, it is clear that foods, such as cow's milk and hen's eggs, can directly provoke flares of AE, particularly in sensitized infants. In general, inhaled allergens and pollen-related foods are of greater importance in older children, adolescents and adults. Clinical studies have revealed that more than 50% of affected children with AE that can be exacerbated by certain foods will react with a worsening of skin eczema either alone or in addition to immediate symptoms. Adolescents and adults may also react to foods, but reactions to 'classical' food allergens, such as hen's eggs and cow's milk, are not as common as in childhood. Some patients with AE do react to pollen-associated foods. Food-induced eczema should not be neglected by the allergologist: On the one hand, food can be a relevant trigger factor of persistent moderate-to-severe AE; on the other hand, unnecessary diets which are not based on a proper diagnosis may lead to malnutrition and additional psychological stress on patients suffering from AE. Eczematous reactions to food can only be diagnosed by a thorough diagnostic procedure, taking into account the patient's history, the degree of sensitization and the clinical relevance of the sensitization. The latter has often to be proven by oral food challenges. Upon oral food challenge it is most important to evaluate the status of the skin with an established score (e.g. SCORAD, EASI) after 24 h and later because otherwise worsening of eczema will be missed.
Whilst the association between eczema and food allergy is well established, the role of dietary manipulation in children with eczema remains controversial. These case histories highlight the differing outcomes that dietary manipulation may have in an infant with early onset, severe eczema and an older child with milder eczema. Management strategies and the evidence to support them are presented, followed by a review of clinical recommendations.
Longitudinal data from population-based studies on the development and persistence of food hypersensitivity (FHS) during childhood are almost absent.
A population-based birth cohort was established, and information on various exposures and symptoms of allergic disease were obtained from questionnaires when the children were 2 months, 1, 2, 4 and 8 years of age. Complete data were available on 3104 children. Children with reported FHS and doctor's diagnosis of food allergy (RDFA) were identified and allocated into transient, intermittent, late-onset and persistent phenotypes. Food allergen-specific IgE-antibodies (abs) to a mix of six common food allergens (fx5) were analysed at 4 and 8 years of age in 1857 children.
The overall prevalence of reported FHS in combination with RDFA should be 3.1% at 1 year to 7.6% at 8 years of age. However, reactions to milk, egg, fish and wheat decreased, whereas an increase was seen for peanuts and tree nuts. Reported reactions to egg, peanuts or tree nuts early in life, as well as IgE-abs to food allergens at the age of 4, increased the risk of FHS at 8 years of age. Furthermore, FHS at young ages increased the risk for asthma, eczema and allergic rhinitis at 8 years of age, even when adjustments were made for children with these symptoms during the first 2 years of life.
The increasing prevalence of FHS up to the age of 8 years probably reflects an increasing prevalence of allergy to birch pollen and pollen-related reactions to foods. Reactions to egg, peanuts and tree nuts early in life increase the risk of FHS at 8 years. Furthermore, reported FHS at young ages, even though transient, seems to increase the risk for other allergic diseases at 8 years of age.
This article reviews possible risk factors and theories for the development of food allergy. It is noted that previous strategies to prevent food allergy through allergen avoidance during pregnancy, breast-feeding, and infancy have more recently been called into question. Alternative hypotheses are examined with respect to food allergy, namely the hygiene hypothesis, the dietary fat hypothesis, the antioxidant hypothesis, and the vitamin D hypotheses. An alternative hypothesis is proposed, suggesting that sensitization to allergen occurs through environmental exposure to allergen through the skin and that consumption of food allergen induces oral tolerance. This hypothesis provides a possible explanation for the close link between eczema and the development of food allergies. It also suggests novel interventional strategies to prevent the development of food allergies.
Cow's milk allergy is the most common childhood food allergy. Previously we noted that children who outgrew their milk allergy had milk-specific IgE antibodies primarily directed against conformational epitopes; those with persistent milk allergy also had IgE antibodies directed against specific sequential epitopes.
Because high temperature largely destroys conformational epitopes, we hypothesized that some children with milk allergy would tolerate extensively heated (baked) milk products.
Children with milk allergy were challenged with heated milk products; heated milk-tolerant subjects were subsequently challenged with unheated milk. Heated milk-tolerant, unheated milk-reactive subjects ingested heated milk products for 3 months and were then re-evaluated. Immune responses were assessed in all subjects; growth and intestinal permeability were followed in heated milk-tolerant subjects.
One hundred children (mean age, 7.5 years; range, 2.1-17.3 years) underwent heated milk challenges. Sixty-eight subjects tolerated extensively heated milk only, 23 reacted to heated milk, and 9 tolerated both heated and unheated milk. Heated milk-reactive subjects had significantly larger skin prick test wheals and higher milk-specific and casein-specific IgE levels than other groups. At 3 months, subjects ingesting heated milk products had significantly smaller skin prick test wheals and higher casein-IgG(4) compared with baseline; other immunologic parameters, growth, and intestinal permeability were not significantly different. Heated milk-reactive subjects had more severe symptoms during heated milk challenge than heated milk-tolerant subjects experienced during their unheated milk challenge.
The majority (75%) of children with milk allergy tolerate heated milk.
Food allergy and atopic dermatitis often occur in the same patients. Food-induced eczema may be perceived as a controversial topic because the immunologic mechanisms have yet to be fully elucidated. Nevertheless, published clinical studies have clearly demonstrated that foods can induce symptoms in a subset of patients with atopic dermatitis. Those at greatest risk are young children in whom eczematous lesions are severe or recalcitrant to therapy. Allergy testing can be helpful but must be applied judiciously. A medical history obtained by a skilled and knowledgeable health care provider is of paramount importance to interpret test results appropriately. Finally, the implementation of proper dietary avoidance can improve symptoms and provide safety from potentially fatal anaphylaxis. However, if inappropriate prescribed, elimination diets can have significant negative nutritional and social consequences.
Learning early about peanut allergy
- Isrctn
- Trial
ISRCTN LEAP Trial. Learning early about peanut allergy. http://controlledtrials.com/ISRCTN94818122/leap. [Accessed 4 January 2010]