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1.  A Randomised Controlled Trial of Ion-Exchange Water Softeners for the Treatment of Eczema in Children 
PLoS Medicine  2011;8(2):e1000395.
In a randomized trial evaluating the effect of installation of ion-exchange water softeners in the households of children with eczema, the researchers found no evidence of improvement in eczema severity as compared to usual care in the study population.
Background
Epidemiological studies and anecdotal reports suggest a possible link between household use of hard water and atopic eczema. We sought to test whether installation of an ion-exchange water softener in the home can improve eczema in children.
Methods and Findings
This was an observer-blind randomised trial involving 336 children (aged 6 months to 16 years) with moderate/severe atopic eczema. All lived in hard water areas (≥200 mg/l calcium carbonate). Participants were randomised to either installation of an ion-exchange water softener plus usual eczema care, or usual eczema care alone. The primary outcome was change in eczema severity (Six Area Six Sign Atopic Dermatitis Score, SASSAD) at 12 weeks, measured by research nurses who were blinded to treatment allocation. Analysis was based on the intent-to-treat population. Eczema severity improved for both groups during the trial. The mean change in SASSAD at 12 weeks was −5.0 (20% improvement) for the water softener group and −5.7 (22% improvement) for the usual care group (mean difference 0.66, 95% confidence interval −1.37 to 2.69, p = 0.53). No between-group differences were noted in the use of topical corticosteroids or calcineurin inhibitors.
Conclusions
Water softeners provided no additional benefit to usual care in this study population. Small but statistically significant differences were found in some secondary outcomes as reported by parents, but it is likely that such improvements were the result of response bias, since participants were aware of their treatment allocation. A detailed report for this trial is also available at http://www.hta.ac.uk.
Trial registration
Current Controlled Trials ISRCTN71423189
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Eczema (sometimes referred to as atopic dermatitis) is a chronic, inflammatory skin condition that affects about 20% of school children in developed countries. Eczema is often associated with other conditions, such as asthma, hay-fever and food allergy and can cause intractable itching leading to thickened skin, bleeding, secondary infection, sleep loss, poor concentration, and psychological distress. Current topical treatments for eczema have side effects, for example, topical corticosteroids may cause skin thinning and the long term safety of topical tacrolimus and pimecrolimus has yet to be determined. Therefore, there is a lot of interest in exploring the benefits of non-pharmacological treatments that have no apparent side effects.
Water hardness (≥200 mg/l calcium carbonate) has become a recent focus of attention.
Why Was This Study Done?
In addition to some epidemiological evidence linking increased water hardness with increased eczema prevalence, there have been widespread anecdotal reports of improvement in the skin of children with eczema when the family has moved from a hard to a soft water area. In addition, some patients report how their eczema symptoms have rapidly improved following the installation of a water softener. However, to date there have been no relevant published trials evaluating the potential benefit of water softeners for eczema. Given the lack of evidence, the high public interest in their potential benefit and the low risk of adverse effects, the researcher conducted a study to assess whether the installation of an ion-exchange water softener reduces the severity of eczema in children with moderate to severe eczema.
What Did the Researchers Do and Find?
The researchers did a pilot study that showed that it was not possible to blind participants to their treatment allocation using real and “dummy” water softener units because the softened water produced more soap suds. So the researchers conducted an observer-blind randomised controlled trial in which they used trained research nurses to conduct an objective assessment of every participant's skin. The researchers recruited 336 children who all lived in hard water areas in England. Eligible children were aged 6 months to 16 years who had a diagnosis of eczema (in line with the UK working party's diagnostic criteria) and an eczema severity score of 10 or over. Participants were randomised to either installation of an ion-exchange water softener plus usual eczema care, or usual eczema care alone. Trained research nurses examined each child's skin at baseline and at 6, 12, and 16 weeks to record changes in eczema severity. The researchers also analysed any changes in symptoms over the study period such as, sleep loss and itchiness, the amount of topical corticosteroid/calcineurin inhibitors used, the Dermatitis Family Impact questionnaire and the health related Quality of Life (children's version).
Although both treatment groups improved in disease severity during the course of the trial, the researchers found no difference between the treatment groups in the main outcome—eczema severity. Similar finding were found for night movement (scratching) and the use of topical medications (creams/ointments applied to the skin), both of which were blinded to intervention status. Nevertheless, parents in the trial did report small health benefits, and just over 50% chose to buy the water softener at the end of the trial because of perceived improvements in the eczema and the wider benefits of water softeners. It is unclear how much of this effect can be explained by prior belief in the effectiveness of the water softeners for the treatment of eczema.
What Do These Findings Mean?
The results of this study suggest that water softeners provide no additional clinical benefit to usual care in children with eczema so the use of ion-exchange water softeners for the treatment of moderate to severe eczema in children should not be recommended. However, it is up to each family to decide whether or not the wider benefits of installing a water softener in their home are sufficient to consider buying one.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000395.
The UK's NHS presents information on eczema for patients and families
MedlinePlus gives information for patients, families, and caregivers on eczema and other similar conditions
The National Eczema Society in the UK provides information and a helpline for eczema patients, families, and caregivers
Medinfo provides information for eczema patients
Wikipedia has more information about water softening (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
doi:10.1371/journal.pmed.1000395
PMCID: PMC3039684  PMID: 21358807
2.  Developmental Profiles of Eczema, Wheeze, and Rhinitis: Two Population-Based Birth Cohort Studies 
PLoS Medicine  2014;11(10):e1001748.
Using data from two population-based birth cohorts, Danielle Belgrave and colleagues examine the evidence for atopic march in developmental profiles for allergic disorders.
Please see later in the article for the Editors' Summary
Background
The term “atopic march” has been used to imply a natural progression of a cascade of symptoms from eczema to asthma and rhinitis through childhood. We hypothesize that this expression does not adequately describe the natural history of eczema, wheeze, and rhinitis during childhood. We propose that this paradigm arose from cross-sectional analyses of longitudinal studies, and may reflect a population pattern that may not predominate at the individual level.
Methods and Findings
Data from 9,801 children in two population-based birth cohorts were used to determine individual profiles of eczema, wheeze, and rhinitis and whether the manifestations of these symptoms followed an atopic march pattern. Children were assessed at ages 1, 3, 5, 8, and 11 y. We used Bayesian machine learning methods to identify distinct latent classes based on individual profiles of eczema, wheeze, and rhinitis. This approach allowed us to identify groups of children with similar patterns of eczema, wheeze, and rhinitis over time.
Using a latent disease profile model, the data were best described by eight latent classes: no disease (51.3%), atopic march (3.1%), persistent eczema and wheeze (2.7%), persistent eczema with later-onset rhinitis (4.7%), persistent wheeze with later-onset rhinitis (5.7%), transient wheeze (7.7%), eczema only (15.3%), and rhinitis only (9.6%). When latent variable modelling was carried out separately for the two cohorts, similar results were obtained. Highly concordant patterns of sensitisation were associated with different profiles of eczema, rhinitis, and wheeze. The main limitation of this study was the difference in wording of the questions used to ascertain the presence of eczema, wheeze, and rhinitis in the two cohorts.
Conclusions
The developmental profiles of eczema, wheeze, and rhinitis are heterogeneous; only a small proportion of children (∼7% of those with symptoms) follow trajectory profiles resembling the atopic march.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Our immune system protects us from viruses, bacteria, and other pathogens by recognizing specific molecules on the invader's surface and initiating a sequence of events that culminates in the death of the pathogen. Sometimes, however, our immune system responds to harmless materials (allergens such as pollen) and triggers allergic, or atopic, symptoms. Common atopic symptoms include eczema (transient dry itchy patches on the skin), wheeze (high pitched whistling in the chest, a symptom of asthma), and rhinitis (sneezing or a runny nose in the absence of a cold or influenza). All these symptoms are very common during childhood, but recent epidemiological studies (examinations of the patterns and causes of diseases in a population) have revealed age-related changes in the proportions of children affected by each symptom. So, for example, eczema is more common in infants than in school-age children. These findings have led to the idea of “atopic march,” a natural progression of symptoms within individual children that starts with eczema, then progresses to wheeze and finally rhinitis.
Why Was This Study Done?
The concept of atopic march has led to the initiation of studies that aim to prevent the development of asthma in children who are thought to be at risk of asthma because they have eczema. Moreover, some guidelines recommend that clinicians tell parents that children with eczema may later develop asthma or rhinitis. However, because of the design of the epidemiological studies that support the concept of atopic march, children with eczema who later develop wheeze and rhinitis may actually belong to a distinct subgroup of children, rather than representing the typical progression of atopic diseases. It is important to know whether atopic march adequately describes the natural history of atopic diseases during childhood to avoid the imposition of unnecessary strategies on children with eczema to prevent asthma. Here, the researchers use machine learning techniques to model the developmental profiles of eczema, wheeze, and rhinitis during childhood in two large population-based birth cohorts by taking into account time-related (longitudinal) changes in symptoms within individuals. Machine learning is a data-driven approach that identifies structure within the data (for example, a typical progression of symptoms) using unsupervised learning of latent variables (variables that are not directly measured but are inferred from other observable characteristics).
What Did the Researchers Do and Find?
The researchers used data from two UK birth cohorts—the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Manchester Asthma and Allergy Study (MAAS)—for their study (9,801 children in total). Both studies enrolled children at birth and monitored their subsequent health at regular review clinics. At each review clinic, information about eczema, wheeze, and rhinitis was collected from the parents using validated questionnaires. The researchers then used these data and machine learning methods to identify groups of children with similar patterns of onset of eczema, wheeze, and rhinitis over the first 11 years of life. Using a type of statistical model called a latent disease profile model, the researchers found that the data were best described by eight latent classes—no disease (51.3% of the children), atopic march (3.1%), persistent eczema and wheeze (2.7%), persistent eczema with later-onset rhinitis (4.7%), persistent wheeze with later-onset rhinitis (5.7%), transient wheeze (7.7%), eczema only (15.3%), and rhinitis only (9.6%).
What Do These Findings Mean?
These findings show that, in two large UK birth cohorts, the developmental profiles of eczema, wheeze, and rhinitis were heterogeneous. Most notably, the progression of symptoms fitted the profile of atopic march in fewer than 7% of children with symptoms. The researchers acknowledge that their study has some limitations. For example, small differences in the wording of the questions used to gather information from parents about their children's symptoms in the two cohorts may have slightly affected the findings. However, based on their findings, the researchers propose that, because eczema, wheeze, and rhinitis are common, these symptoms often coexist in individuals, but as independent entities rather than as a linked progression of symptoms. Thus, using eczema as an indicator of subsequent asthma risk and assigning “preventative” measures to children with eczema is flawed. Importantly, clinicians need to understand the heterogeneity of patterns of atopic diseases in children and to communicate this variability to parents when advising them about the development and resolution of atopic symptoms in their children.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001748.
The UK National Health Service Choices website provides information about eczema (including personal stories), asthma (including personal stories), and rhinitis
The US National Institute of Allergy and Infectious Diseases provides information about atopic diseases
The UK not-for-profit organization Allergy UK provides information about atopic diseases and a description of the atopic march
MedlinePlus encyclopedia has pages on eczema, wheezing, and rhinitis (in English and Spanish)
MedlinePlus provides links to further resources about allergies, eczema, and asthma (in English and Spanish)
Information about ALSPAC and MAAS is available
Wikipedia has pages on machine learning and latent disease profile models (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
doi:10.1371/journal.pmed.1001748
PMCID: PMC4204810  PMID: 25335105
3.  Gene-Environment Interaction in the Onset of Eczema in Infancy: Filaggrin Loss-of-Function Mutations Enhanced by Neonatal Cat Exposure  
PLoS Medicine  2008;5(6):e131.
Background
Loss-of-function variants in the gene encoding filaggrin (FLG) are major determinants of eczema. We hypothesized that weakening of the physical barrier in FLG-deficient individuals may potentiate the effect of environmental exposures. Therefore, we investigated whether there is an interaction between FLG loss-of-function mutations with environmental exposures (pets and dust mites) in relation to the development of eczema.
Methods and Findings
We used data obtained in early life in a high-risk birth cohort in Denmark and replicated the findings in an unselected birth cohort in the United Kingdom. Primary outcome was age of onset of eczema; environmental exposures included pet ownership and mite and pet allergen levels. In Copenhagen (n = 379), FLG mutation increased the risk of eczema during the first year of life (hazard ratio [HR] 2.26, 95% confidence interval [CI] 1.27–4.00, p = 0.005), with a further increase in risk related to cat exposure at birth amongst children with FLG mutation (HR 11.11, 95% CI 3.79–32.60, p < 0.0001); dog exposure was moderately protective (HR 0.49, 95% CI 0.24–1.01, p = 0.05), but not related to FLG genotype. In Manchester (n = 503) an independent and significant association of the development of eczema by age 12 mo with FLG genotype was confirmed (HR 1.95, 95% CI 1.13–3.36, p = 0.02). In addition, the risk increased because of the interaction of cat ownership at birth and FLG genotype (HR 3.82, 95% CI 1.35–10.81, p = 0.01), with no significant effect of the interaction with dog ownership (HR 0.59, 95% CI 0.16–2.20, p = 0.43). Mite-allergen had no effects in either cohort. The observed effects were independent of sensitisation.
Conclusions
We have demonstrated a significant interaction between FLG loss-of-function main mutations (501x and 2282del4) and cat ownership at birth on the development of early-life eczema in two independent birth cohorts. Our data suggest that cat but not dog ownership substantially increases the risk of eczema within the first year of life in children with FLG loss-of-function variants, but not amongst those without. FLG-deficient individuals may need to avoid cats but not dogs in early life.
In two independent cohorts of children, Hans Bisgaard and colleagues show an association between mutations in the filaggrin gene (FLG) and ownership of cats, but not dogs, with development of eczema.
Editors' Summary
Background.
Eczema is a skin condition characterized by dry, red, and itchy patches on the skin. Eczema is associated with asthma and allergy, though allergy rarely plays a role in development or severity of eczema. Eczema usually begins during infancy, typically on the face, scalp, neck, extensor sides of the forearms, and legs. Up to one in five infants develops eczema, but in more than half of them, the condition improves or disappears completely before they are 15 years old. If eczema persists into adulthood, it usually affects the face and the skin inside the knees and elbows. There is no cure for eczema but it can be controlled by avoiding anything that makes its symptoms worse. These triggers include irritants such as wool, strong soaps, perfumes, and dry environments. A good skin-care routine and frequent moisturizing can also help to keep eczema under control, but in many cases, corticosteroid creams and ointments may be necessary to reduce inflammation.
Why Was This Study Done?
Eczema tends to run in families. This suggests that eczema is caused by genetic factors as well as by environmental factors. Recently, researchers discovered that two common “loss-of-function” variants in the gene encoding filaggrin (FLG) predispose people to eczema. People who inherit one or two defective genes make no filaggrin, a protein that normally forms a physical barrier in the skin that protects the body from potentially harmful substances in the environment. Might the weakening of this barrier in filaggrin-deficient individuals affect their responses to environmental substances to which the skin is exposed? In this study, the researchers test this potential explanation for how genetic and environmental factors (in particular, exposure to pets) might interact to determine an individual's chances of developing eczema.
What Did the Researchers Do and Find?
To test their hypothesis, the researchers studied two independent groups of infants during their first year of life—a high-risk group consisting of infants born in Copenhagen, Denmark to mothers with asthma and a group of infants born to women from the general population in Manchester, United Kingdom. The researchers determined which FLG variants each child had inherited and classified those with either one or two defective copies of FLG as having an FLG mutation. They determined pet exposure in early life by asking whether a dog or a cat was living in the parental home when the child was born (“pet ownership”) and then analyzed how these genetic and environmental factors affected the age of onset of eczema. In both groups, children with FLG mutations were twice as likely to develop eczema during the first year of life as children without FLG mutations. For children without FLG mutations, cat ownership at birth had no effect on eczema risk but for children with FLG mutations, cat ownership at birth (but not dog ownership) further increased the risk of developing eczema.
What Do These Findings Mean?
These findings show that FLG mutations and cat ownership at birth interact to determine the chances of a child developing eczema during the first year of life. They provide support, therefore, for the researchers' suggestion that the weakening of the skin's protective barrier that is caused by filaggrin deficiency increases the child's susceptibility to factors associated with cat exposure. Only a small number of children in this study carried FLG mutations and were exposed to cats from birth, so these findings need confirming in independent studies. In addition, it is still not clear how exposure to cats drives the development of eczema. Allergy was not the mechanism as the FLG-deficient children exposed to cat and who developed eczema did not develop cat-specific immunoglobin E antibodies. Nevertheless, these findings suggest that, to reduce their risk of developing eczema, filaggrin-deficient individuals should avoid cats (but not dogs) during the first few months of life.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050131.
The MedlinePlus Encyclopedia has a page on eczema (in English and Spanish); links to further information are provided by MedlinePlus
EczemaNet is a comprehensive online information resource about eczema provided by the American Academy of Dermatologists
The US National Institute of Arthritis and Musculoskeletal and Skin Diseases provides information on eczema
The UK National Health Service Direct health encyclopedia provides information for patients on eczema (in several languages)
The Copenhagen Studies on Asthma in Childhood (COPSAC) and Manchester Asthma and Allergy Study (MAAS) Web sites provide more information about the children involved in this research
doi:10.1371/journal.pmed.0050131
PMCID: PMC2504043  PMID: 18578563
4.  Eczema 
Clinical Evidence  2011;2011:1716.
Introduction
Eczema, as defined by the World Allergy Organization (WAO) revised nomenclature in 2003, affects 15% to 20% of school children and 2% to 5% of adults worldwide. About 50% of people with eczema demonstrate atopy, with specific immunoglobulin E responses to allergens.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of topical medical treatments, and dietary interventions in adults and children with established eczema? What are the effects of breastfeeding, reducing allergens, or dietary interventions for primary prevention of eczema in predisposed infants? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 54 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: breastfeeding, controlling house dust mites, corticosteroids, dietary exclusion of eggs or cow's milk, elementary diets, emollients, essential fatty oils, few-foods diet, multivitamins, pimecrolimus, probiotics, pyridoxine, reducing maternal dietary allergens, tacrolimus, vitamin E, and zinc supplements.
Key Points
Eczema, as defined by the World Allergy Organization (WAO) revised nomenclature in 2003, affects 15% to 20% of school children worldwide and 2% to 5% of adults. Only about 50% of people with eczema demonstrate allergic sensitisation. Remission occurs in two-thirds of children by the age of 15 years, but relapses may occur later.
Emollients are generally considered to be effective for treating the symptoms of eczema. However, the few small short-term RCTs that have been done so far do not confirm this. Sufficiently powered long-term RCTs are needed to clarify the role of emollients in the treatment of eczema.
Corticosteroids improve clearance of lesions and decrease relapse rates compared with placebo in adults and children with eczema, although we don't know which is the most effective corticosteroid or the most effective dosing regimen. Topical corticosteroids seem to have few adverse effects when used intermittently, but if they are of potent or very potent strength, they may cause burning, skin thinning, and telangiectasia, especially in children.
The calcineurin inhibitors pimecrolimus and tacrolimus improve clearance of lesions compared with placebo and may have a role in people in whom corticosteroids are contraindicated. They also seem suitable for topical use in body areas where the skin is particularly thin, such as the face.
CAUTION: An association has been suggested between pimecrolimus and tacrolimus and skin cancer in animal models. Although this association has not been confirmed in humans, calcineurin inhibitors should be used only when other treatments have failed.
We don't know whether vitamin E or multivitamins reduce symptoms in adults with eczema or whether pyridoxine, zinc supplementation, exclusion diets, or elemental diets are effective in children with eczema, as there are insufficient good-quality studies. Probiotics do not seem to reduce symptoms in children with established eczema. Essential fatty acids, such as evening primrose oil, blackcurrant seed oil, or fish oil, do not seem to reduce symptoms in people with eczema.
We don't know whether control of house dust mites or maternal dietary restriction can prevent the development of eczema in children. Observational data suggest that exclusive breastfeeding for at least 3 months does not reduce eczema risk and there is no evidence to suggest that exclusive breastfeeding alleviates eczema symptoms, unless a child is allergic to cow's milk protein.Introduction of probiotics in the last trimester of pregnancy and during breastfeeding may reduce the risk of eczema in the baby, although it remains unclear whether both antenatal and postnatal supplementation together yields the strongest protective effect. It is equally unclear which strains of probiotics are most effective.
PMCID: PMC3217753  PMID: 21609512
5.  Active or Passive Exposure to Tobacco Smoking and Allergic Rhinitis, Allergic Dermatitis, and Food Allergy in Adults and Children: A Systematic Review and Meta-Analysis 
PLoS Medicine  2014;11(3):e1001611.
In a systematic review and meta-analysis, Bahi Takkouche and colleagues examine the associations between exposure to tobacco smoke and allergic disorders in children and adults.
Please see later in the article for the Editors' Summary
Background
Allergic rhinitis, allergic dermatitis, and food allergy are extremely common diseases, especially among children, and are frequently associated to each other and to asthma. Smoking is a potential risk factor for these conditions, but so far, results from individual studies have been conflicting. The objective of this study was to examine the evidence for an association between active smoking (AS) or passive exposure to secondhand smoke and allergic conditions.
Methods and Findings
We retrieved studies published in any language up to June 30th, 2013 by systematically searching Medline, Embase, the five regional bibliographic databases of the World Health Organization, and ISI-Proceedings databases, by manually examining the references of the original articles and reviews retrieved, and by establishing personal contact with clinical researchers. We included cohort, case-control, and cross-sectional studies reporting odds ratio (OR) or relative risk (RR) estimates and confidence intervals of smoking and allergic conditions, first among the general population and then among children.
We retrieved 97 studies on allergic rhinitis, 91 on allergic dermatitis, and eight on food allergy published in 139 different articles. When all studies were analyzed together (showing random effects model results and pooled ORs expressed as RR), allergic rhinitis was not associated with active smoking (pooled RR, 1.02 [95% CI 0.92–1.15]), but was associated with passive smoking (pooled RR 1.10 [95% CI 1.06–1.15]). Allergic dermatitis was associated with both active (pooled RR, 1.21 [95% CI 1.14–1.29]) and passive smoking (pooled RR, 1.07 [95% CI 1.03–1.12]). In children and adolescent, allergic rhinitis was associated with active (pooled RR, 1.40 (95% CI 1.24–1.59) and passive smoking (pooled RR, 1.09 [95% CI 1.04–1.14]). Allergic dermatitis was associated with active (pooled RR, 1.36 [95% CI 1.17–1.46]) and passive smoking (pooled RR, 1.06 [95% CI 1.01–1.11]). Food allergy was associated with SHS (1.43 [1.12–1.83]) when cohort studies only were examined, but not when all studies were combined.
The findings are limited by the potential for confounding and bias given that most of the individual studies used a cross-sectional design. Furthermore, the studies showed a high degree of heterogeneity and the exposure and outcome measures were assessed by self-report, which may increase the potential for misclassification.
Conclusions
We observed very modest associations between smoking and some allergic diseases among adults. Among children and adolescents, both active and passive exposure to SHS were associated with a modest increased risk for allergic diseases, and passive smoking was associated with an increased risk for food allergy. Additional studies with detailed measurement of exposure and better case definition are needed to further explore the role of smoking in allergic diseases.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
The immune system protects the human body from viruses, bacteria, and other pathogens. Whenever a pathogen enters the body, immune system cells called T lymphocytes recognize specific molecules on its surface and release chemical messengers that recruit and activate other types of immune cells, which then attack the pathogen. Sometimes, however, the immune system responds to harmless materials (for example, pollen; scientists call these materials allergens) and triggers an allergic disease such as allergic rhinitis (inflammation of the inside of the nose; hay fever is a type of allergic rhinitis), allergic dermatitis (also known as eczema, a disease characterized by dry, itchy patches on the skin), and food allergy. Recent studies suggest that all these allergic (atopic) diseases are part of a continuous state called the “atopic march” in which individuals develop allergic diseases in a specific sequence that starts with allergic dermatitis during infancy, and progresses to food allergy, allergic rhinitis, and finally asthma (inflammation of the airways).
Why Was This Study Done?
Allergic diseases are extremely common, particularly in children. Allergic rhinitis alone affects 10%–30% of the world's population and up to 40% of children in some countries. Moreover, allergic diseases are becoming increasingly common. Allergic diseases affect the quality of life of patients and are financially costly to both patients and health systems. It is important, therefore, to identify the factors that cause or potentiate their development. One potential risk factor for allergic diseases is active or passive exposure to tobacco smoke. In some countries up to 80% of children are exposed to second-hand smoke so, from a public health point of view, it would be useful to know whether exposure to tobacco smoke is associated with the development of allergic diseases. Here, the researchers undertake a systematic review (a study that uses predefined criteria to identify all the research on a given topic) and a meta-analysis (a statistical approach for combining the results of several studies) to investigate this issue.
What Did the Researchers Do and Find?
The researchers identified 196 observational studies (investigations that observe outcomes in populations without trying to affect these outcomes in any way) that examined the association between smoke exposure and allergic rhinitis, allergic dermatitis, or food allergy. When all studies were analyzed together, allergic rhinitis was not associated with active smoking but was slightly associated with exposure to second-hand smoke. Specifically, compared to people not exposed to second-hand smoke, the pooled relative risk (RR) of allergic rhinitis among people exposed to second-hand smoke was 1.10 (an RR of greater than 1 indicates an increased risk of disease development in an exposed population compared to an unexposed population). Allergic dermatitis was associated with both active smoking (RR = 1.21) and exposure to second-hand smoke (RR = 1.07). In the populations of children and adolescents included in the studies, allergic rhinitis was associated with both active smoking and exposure to second-hand smoke (RRs of 1.40 and 1.09, respectively), as was allergic dermatitis (RRs of 1.36 and 1.06, respectively). Finally food allergy was associated with exposure to second-hand smoke (RR = 1.43) when cohort studies (a specific type of observational study) only were examined but not when all the studies were combined.
What Do These Findings Mean?
These findings provide limited evidence for a weak association between smoke exposure and allergic disease in adults but suggest that both active and passive smoking are associated with a modestly increased risk of allergic diseases in children and adolescents. The accuracy of these findings may be affected by the use of questionnaires to assess smoke exposure and allergic disease development in most of the studies in the meta-analysis and by the possibility that individuals exposed to smoke may have shared other characteristics that were actually responsible for their increased risk of allergic diseases. To shed more light on the role of smoking in allergic diseases, additional studies are needed that accurately measure exposure and outcomes. However, the present findings suggest that, in countries where many people smoke, 14% and 13% of allergic rhinitis and allergic dermatitis, respectively, among children may be attributable to active smoking. Thus, the elimination of active smoking among children and adolescents could prevent one in seven cases of allergic rhinitis and one in eight cases of allergic dermatitis in such countries.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001611.
The UK National Health Service Choices website provides information about allergic rhinitis, hay fever (including personal stories), allergic dermatitis (including personal stories), and food allergy (including personal stories)
The US National Institute of Allergy and Infectious Disease provides information about allergic diseases
The UK not-for-profit organization Allergy UK provides information about all aspects of allergic diseases and a description of the atopic march
MedlinePlus encyclopedia has pages on allergic rhinitis and allergic dermatitis (in English and Spanish)
MedlinePlus provides links to further resources about allergies, eczema, and food allergy (in English and Spanish)
doi:10.1371/journal.pmed.1001611
PMCID: PMC3949681  PMID: 24618794
6.  Eczema in early childhood is strongly associated with the development of asthma and rhinitis in a prospective cohort 
BMC Dermatology  2012;12:11.
Background
This study aimed to estimate the association between eczema in early childhood and the onset of asthma and rhinitis later in life in children.
Methods
A total of 3,124 children aged 1–2 years were included in the Dampness in Building and Health (DBH) study in the year 2000, and followed up 5 years later by a parental questionnaire based on an International Study of Asthma and Allergies in Childhood protocol. The association between eczema in early childhood and the incidence of asthma and rhinitis later in life was estimated by univariable and multivariable logistic regression modelling.
Results
The prevalence of eczema in children aged 1–2 years was 17.6% at baseline. Children with eczema had a 3-fold increased odds of developing asthma (adjusted odds ratio [aOR], 3.07; 95% confidence interval (CI) 1.79–5.27), and a nearly 3-fold increased odds of developing rhinitis (aOR, 2.63; 1.85–3.73) at follow-up compared with children without eczema, adjusted for age, sex, parental allergic disease, parental smoking, length of breastfeeding, site of living, polyvinylchloride flooring material, and concomitant allergic disease. When eczema was divided into subgroups, moderate to severe eczema (aOR, 3.56; 1.62–7.83 and aOR, 3.87; 2.37–6.33, respectively), early onset of eczema (aOR, 3.44; 1.94–6.09 and aOR, 4.05; 2.82–5.81; respectively), and persistence of eczema (aOR, 5.16; 2.62–10.18 and aOR, 4.00; 2.53–6.22, respectively) further increased the odds of developing asthma and rhinitis. Further independent risk factors increasing the odds of developing asthma were a parental history of allergic disease (aOR, 1.83; 1.29–2.60) and a period of breast feeding shorter than 6 months (aOR, 1.57; 1.03–2.39). The incidence of rhinitis was increased for parental history of allergic disease (aOR, 2.00; 1.59–2.51) and polyvinylchloride flooring (aOR, 1.60; 1.02–2.51).
Conclusion
Eczema in infancy is associated with development of asthma and rhinitis during the following 5-year period, and eczema is one of the strongest risk factors. Early identification is valuable for prediction of the atopic march.
doi:10.1186/1471-5945-12-11
PMCID: PMC3469362  PMID: 22839963
7.  Overview of Reviews The prevention of eczema in infants and children: an overview of Cochrane and non-Cochrane reviews 
Background
Eczema is the most common inflammatory skin disease of childhood, characterized by an itchy red rash that usually involves the face and skin folds. There is currently no curative treatment for eczema, so the reduction of eczema incidence through disease prevention is a desirable goal. Potential interventions for preventing eczema include exclusive breastfeeding, hydrolysed protein formulas and soy formulas when bottle feeding, maternal antigen avoidance, omega oil supplementation, prebiotics and probiotics.
Objectives
This overview of reviews aims to present the current body of data from Cochrane and non-Cochrane reviews to provide the most up-to-date evidence on the efficacy and safety of interventions to prevent eczema in infants and children at different risk levels for developing allergic disease.
Methods
Our pool of Cochrane and non-Cochrane reviews came from the 2010 United Kingdom National Health Service (NHS) Evidence Skin Disorders Annual Evidence Updates Mapping Exercise on Atopic Eczema. This group used a comprehensive search strategy last conducted in August 2010 to identify all systematic reviews on eczema prevention. We identified all reviews that met our pre-specified inclusion criteria, and data were extracted, analysed, compiled into tables and synthesized using quantitative and qualitative methods.
Main results
Seven systematic reviews containing 39 relevant trials with 11 897 participants were included in this overview. Overall, there was no clear evidence that any of the main interventions reviewed reduced eczema incidence. In subgroup analyses of infants at high risk of allergic disease, an observational study found that exclusive breastfeeding for at least six months compared with introduction of solids at three to six months decreased the incidence of eczema by 60% (risk ratio (RR): 0.40; 95% confidence interval (CI): 0.21, 0.78), and a randomized controlled trial found that prebiotics compared with no prebiotics decreased incidence by 58% (RR: 0.42; 95% CI: 0.21, 0.84). However, each of these findings was based on the results of a single small trial, and no intervention reduced eczema incidence beyond the first two years of life. Although we pre-specified incidence of atopic eczema (i.e. eczema associated with immunoglobulin E (IgE) sensitization) as a primary outcome, data on whether participants diagnosed with eczema were truly atopic were largely lacking from systematic reviews. Similarly, data on atopy, measured using skin prick tests or specific IgE tests to allergens, were not reported in many reviews. No interventions were found to decrease atopy when reported. Adverse events data were generally lacking, but data from a trial of probiotics versus no probiotics showed significantly more spitting up in the first one (RR: 1.88; 95% CI: 1.03, 3.45) and two (RR: 1.69; 95% CI: 1.02, 2.80) months of life, but no overall increase in risk of gastrointestinal symptoms in the first year.
Authors’ conclusions
Although there is currently no clear evidence showing that any of the interventions examined in this overview prevent eczema in participants not selected for risk of allergic disease, there is some evidence that exclusive breastfeeding for at least six months and prebiotics might reduce eczema incidence in high-risk participants. However, these conclusions are based on limited evidence with methodological shortcomings. Future research on prevention of eczema is needed and should examine different types of hydrolysed formulas, prebiotics and probiotics, as well as enhancement of the skin barrier and other novel approaches in infants at different risk levels for developing allergic disease.
doi:10.1002/ebch.827
PMCID: PMC3399595  PMID: 22822349
eczema; overview; skin disease; systematic review
8.  Filaggrin gene defects and risk of developing allergic sensitisation and allergic disorders: systematic review and meta-analysis 
Objective 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.
Design Systematic review and meta-analysis.
Data sources 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.
Study selection Genetic epidemiological studies (family, case-control) of the association between filaggrin gene defects and allergic sensitisation or allergic disorders.
Data extraction 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.
Data synthesis 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.
Conclusions 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.
doi:10.1136/bmj.b2433
PMCID: PMC2714678  PMID: 19589816
9.  Potential mechanisms for the association between fall birth and food allergy 
Allergy  2012;67(6):775-782.
BACKGROUND
Season of birth has been reported as a risk factor for food allergy, but the mechanisms by which it acts are unknown.
METHODS
Two populations were studied; 5862 children from the National Health and Nutrition Examination Survey (NHANES) III, 1514 well-characterized food allergic children from the Johns Hopkins Pediatric Allergy Clinic (JHPAC). Food allergy was defined as self report of an acute reaction to a food (NHANES), or as milk, egg and peanut allergy. Logistic regression compared fall or non-fall birth between (1) food allergic and non-allergic subjects in NHANES, adjusted for ethnicity, age, income and sex, and (2) JHPAC subjects and the general Maryland population. For NHANES, stratification by ethnicity and for JHPAC, eczema, was examined.
RESULTS
Fall birth was more common among food allergic subjects in both NHANES (OR: 1.91, 95%CI: 1.31–2.77) and JHPAC/Maryland (OR: 1.31, 95%CI: 1.18–1.47). Ethnicity interacted with season (OR 2.34, 95%CI 1.43–3.82 for Caucasians, OR 1.19, 95%CI 0.77–1.86 for non-Caucasians, p=0.04 for interaction), as did eczema (OR 1.47, 95%CI 1.29–1.67 with eczema, OR 1.00, 95%CI 0.80–1.23 without eczema, p=0.002 for interaction).
Conclusions
Fall birth is associated with increased risk of food allergy, and this risk is greatest among those most likely to have seasonal variation in vitamin D during infancy (Caucasians) and those at risk for skin barrier dysfunction (subjects with a history of eczema), suggesting that vitamin D and the skin barrier may be implicated in seasonal associations with food allergy.
doi:10.1111/j.1398-9995.2012.02823.x
PMCID: PMC3349789  PMID: 22515802
food allergy; season of birth; eczema; vitamin D
10.  Probiotics in the Treatment and Prevention of Allergy in Children 
Several fold increase in allergic diseases in developed, high-income countries during recent decades is attributed to environmental changes such as urbanization with improved hygiene. This, together with conquering severe bacterial infections during childhood, has reduced the microbial stimulation of the developing immune system of infants. Studies on the pathogenesis of allergy both in man and experimental animal have shown the importance of commensal bacteria in the gastrointestinal tract in stimulating and directing the immune system. The interest in modulating commensal bacterial flora with probiotics to prevent and treat allergy has multiplied in recent years.
In the present review we report results on randomized, controlled studies in which childhood atopic eczema was treated or which aimed to prevent development of allergy during childhood.
Nine studies with 639 patients have looked at the effect of probiotics in treatment of eczema. While 3 studied showed no effect, other studies suggested a moderate benefit of the use of probiotics on the severity of eczema. Studies suggested that the effect may be seen particularly in patients with food allergy and/or sensitization.
Nine studies have reported on the prevention of allergy on 6 study population with altogether 1989 high risk infants. While the early study reporting the development of allergy at ages 2, 4 and 7 years showed a marked reduction of eczema in 77 treated infants, later studies have failed to show similar success. Two studies showed no effect. In the largest study with more than 900 children at age 2 atopic eczema was reduced by 20%, but at age 5 positive effect was present in only the subgroup of children who had born by cesarean section. None of studies has reported adverse effects of probiotics in infants.
Result in both treatment and prevention studies are quite variable, the major reason being the use of different strains of probiotic bacteria and varying types of intervention. Even if the results are encouraging, we need a stronger effect. This may be reached by finding new strains of probiotics affecting stronger stimulation of immune system, together with longer lasting and varying treatment schedules. However, safety issues have to be observed.
doi:10.1097/WOX.0b013e3181a45ee5
PMCID: PMC3651021  PMID: 23283013
probiotics; prevention of allergic diseases; treatment of allergic diseases; atopic eczema
11.  Prevalence and co-occurrence of parentally reported possible asthma and allergic manifestations in pre-school children 
BMC Public Health  2013;13:764.
Background
The aim of this study was to make an in-depth analysis of the prevalence and co-occurrence in pre-school children of possible asthma and atopic manifestations.
Methods
In Sweden 74%-84% of preschool children, depending on age, attend municipality organised day-care centres. Parents of 5,886 children 1–6 years of age, sampled from day-care centres in 62 municipalities all over Sweden, responded to a postal questionnaire regarding symptoms indicating prevalent possible asthma, allergic rhinitis, eczema, and food, furred pet and pollen allergy and other data in their children. Possible asthma was defined as any of the four criteria wheezing four times or more during the last year, physician diagnosis and current wheezing, ever had asthma and current wheezing, and current use of inhalation steroids, all based on questionnaire responses.
Results
The overall prevalence of possible asthma was 8.9%, of eczema 21.7%, of rhinitis 8.1%, and of food allergy 6.6%. There was a highly significant co-occurrence between possible asthma and all atopic manifestations, 35.7% having any of the manifestations. Presence of pet allergy was the manifestation showing the closest co-occurrence with presence of possible asthma, presence of pollen allergy with presence of rhinitis, and presence of food allergy with presence of eczema. Assessed from plots of age-specific prevalence of possible asthma, rhinitis, eczema and food allergy, the prevalence of all manifestations increased from one to three years of age and then decreased, except for rhinitis where the prevalence increased until six years of age, indicating no specific ordered sequence.
Conclusions
Parentally reported possible asthma, eczema and food allergy had a curvilinear prevalence course across age with a maximum at age 3, while rhinitis prevalence increased consistently with age. Co-occurrence between possible asthma and atopic manifestations was common, and some combinations were more common than others, but there was no evidence of a specific ordered onset sequence.
doi:10.1186/1471-2458-13-764
PMCID: PMC3765705  PMID: 23953349
12.  Maternal fish and shellfish consumption and wheeze, eczema and food allergy at age two: a prospective cohort study in Brittany, France 
Environmental Health  2013;12:102.
Background
Environmental exposures, including dietary contaminants, may influence the developing immune system. This study assesses the association between maternal pre-parturition consumption of seafood and wheeze, eczema, and food allergy in preschool children. Fish and shellfish were studied separately as they differ according to their levels of omega-3 polyunsaturated fatty acids (which have anti-allergic properties) and their levels of contaminants.
Methods
The PELAGIE cohort included 3421 women recruited at the beginning of pregnancy. Maternal fish and shellfish intake was measured at inclusion by a food frequency questionnaire. Wheeze, eczema, and food allergy were evaluated by a questionnaire completed by the mother when the child was 2 years old (n = 1500). Examination of the associations between seafood intake and outcomes took major confounders into account. Complementary sensitivity analyses with multiple imputation enabled us to handle missing data, due mostly to attrition.
Results
Moderate maternal pre-parturition fish intake (1 to 4 times a month) was, at borderline significance, associated with a lower risk of wheeze (adjusted OR = 0.69 (0.45-1.05)) before age 2, compared with low intake (< once/month). This result was not, however, consistent: after multiple imputation, the adjusted OR was 0.86 (0.63-1.17). Shellfish intake at least once a month was associated with a higher risk of food allergy before age 2 (adjusted OR = 1.62 (1.11-2.37)) compared to low or no intake (< once/month). Multiple imputation confirmed this association (adjusted OR = 1.52 (1.05-2.21)).
Conclusions
This study suggests that maternal pre-parturition shellfish consumption may increase the risk of food allergy. Further large-scale epidemiologic studies are needed to corroborate these results, identify the contaminants or components of shellfish responsible for the effects observed, determine the persistence of the associations seen at age 2, and investigate potential associations with health effects observable at later ages, such as allergic asthma.
doi:10.1186/1476-069X-12-102
PMCID: PMC3893486  PMID: 24295221
Fish intake; Shellfish intake; Pregnancy; Wheeze; Allergy; Children
13.  441 Patterns of Food Allergens in Kenyan Children 
The World Allergy Organization Journal  2012;5(Suppl 2):S157-S158.
Background
To determine the patterns of food allergens in children presenting to pediatric gastroenterology clinic at the Aga Khan University Hospital, Nairobi.
Methods
This data includes children evaluated from March to November, 2010.All the children presenting for evaluation of various gastrointestinal symptoms and who had positive history of atopy in at least one first degree relative were included. History of reccurent cough was sought and the skin was examined for eczema. Skin Prick Test was perfomed by an expert in allergy and immunology. Prick to Prick Test was done for local foods where commercial antigens were not available. Positive tests were followed by an exclusion and rechallenge progamme but this was excluded from analysis due to poor compliance. Analysis was performed to determine frequencies and associations of the different gastrointestinal symptoms and food allergens. Both skin Prick and Prick to Prick results were analysed together.
Results
The commonest food allergens in order of frequency were cow milk (65%), egg (35%), beef (26%), beans (14%), chicken, corn, wheat, soya and rice (9%), fish (8%) and peanut (5%).Common local infant complementary foods including potatoes, bananas and vegetables all tested positive in 4% of the children. Pumpkin tested positive in one infant who had presented with rectal bleeding. Majority of the children had positive tests to multiple foods. Only 14% of the children had negative tests. The commonest gastrointestinal (GI) symptoms were abdominal pain (38%), constipation (36%), vomiting (14%), diarrhoea (11%), failure to thrive (9%) and colics (3%). Majority of the children had multiple GI symptoms. Eczema and cough were associated symptoms in 9% and 3% of the children respectively.
Conclusions
The prevalence of food allergy as suggested by this study is high in Kenyan children and contributes signficantly towards gastrointestinal morbidity. While cow milk, egg and beef are the commonest allergens, the emerging allergy to local infant complementary foods is also significant. The high frequency of multiple allergens partly contributed to poor compliance in the exclusion rechallenge programme due to lack of options on alternative foods.
doi:10.1097/01.WOX.0000412204.60821.e4
PMCID: PMC3512893
14.  Prenatal Exposure to Butylbenzyl Phthalate and Early Eczema in an Urban Cohort 
Environmental Health Perspectives  2012;120(10):1475-1480.
Background: Recent cross-sectional studies suggest a link between butylbenzyl phthalate (BBzP) in house dust and childhood eczema.
Objectives: We aimed to evaluate whether concentrations of monobenzyl phthalate (MBzP), the main BBzP metabolite in urine, during pregnancy are associated prospectively with eczema in young children, and whether this association varies by the child’s sensitization to indoor allergens or serological evidence of any allergies.
Methods: MBzP was measured in spot urine samples during the third trimester of pregnancy from 407 African-American and Dominican women residing in New York City in 1999–2006. Repeated questionnaires asked mothers whether their doctor ever said their child had eczema. Child blood samples at 24, 36, and 60 months of age were analyzed for total, anti-cockroach, dust mite, and mouse IgE. Relative risks (RR) were estimated with multivariable modified Poisson regression. Analyses included a multinomial logistic regression model for early- and late-onset eczema versus no eczema through 60 months of age.
Results: MBzP was detected in > 99% of samples (geometric mean = 13.6; interquartile range: 5.7–31.1 ng/mL). By 24 months, 30% of children developed eczema, with the proportion higher among African Americans (48%) than among Dominicans (21%) (p < 0.001). An interquartile range increase in log MBzP concentration was associated positively with early-onset eczema (RR = 1.52 for eczema by 24 months; 95% confidence interval: 1.21, 1.91, p = 0.0003, n = 113 reporting eczema/376 total sample), adjusting for urine specific gravity, sex, and race/ethnicity. MBzP was not associated with allergic sensitization, nor did seroatopy modify consistently the MBzP and eczema association.
Conclusions: Prenatal exposure to BBzP may influence the risk of developing eczema in early childhood.
doi:10.1289/ehp.1104544
PMCID: PMC3491925  PMID: 22732598
butylbenzyl phthalate; eczema; plasticizers
15.  A global survey of changing patterns of food allergy burden in children 
While food allergies and eczema are among the most common chronic non-communicable diseases in children in many countries worldwide, quality data on the burden of these diseases is lacking, particularly in developing countries. This 2012 survey was performed to collect information on existing data on the global patterns and prevalence of food allergy by surveying all the national member societies of the World Allergy Organization, and some of their neighbouring countries. Data were collected from 89 countries, including published data, and changes in the health care burden of food allergy. More than half of the countries surveyed (52/89) did not have any data on food allergy prevalence. Only 10% (9/89) of countries had accurate food allergy prevalence data, based on oral food challenges (OFC). The remaining countries (23/89) had data largely based on parent-reporting of a food allergy diagnosis or symptoms, which is recognised to overestimate the prevalence of food allergy. Based on more accurate measures, the prevalence of clinical (OFC proven) food allergy in preschool children in developed countries is now as high as 10%. In large and rapidly emerging societies of Asia, such as China, where there are documented increases in food allergy, the prevalence of OFC-proven food allergy is now around 7% in pre-schoolers, comparable to the reported prevalence in European regions. While food allergy appears to be increasing in both developed and developing countries in the last 10–15 years, there is a lack of quality comparative data. This survey also highlights inequities in paediatric allergy services, availability of adrenaline auto-injectors and standardised National Anaphylaxis Action plans. In conclusion, there remains a need to gather more accurate data on the prevalence of food allergy in many developed and developing countries to better anticipate and address the rising community and health service burden of food allergy.
doi:10.1186/1939-4551-6-21
PMCID: PMC3879010  PMID: 24304599
Food allergy; Allergic disease; Allergy epidemic; Allergy prevention; Food allergens
16.  Early eczema and the risk of childhood asthma: a prospective, population-based study 
BMC Pediatrics  2012;12:168.
Background
Severe eczema in young children is associated with an increased risk of developing asthma and rhino-conjunctivitis. In the general population, however, most cases of eczema are mild to moderate. In an unselected cohort, we studied the risk of current asthma and the co-existence of allergy-related diseases at 6 years of age among children with and without eczema at 2 years of age.
Methods
Questionnaires assessing various environmental exposures and health variables were administered at 2 years of age. An identical health questionnaire was completed at 6 years of age. The clinical investigation of a random subsample ascertained eczema diagnoses, and missing data were handled by multiple imputation analyses.
Results
The estimate for the association between eczema at 2 years and current asthma at 6 years was OR=1.80 (95% CI 1.10-2.96). Four of ten children with eczema at 6 years had the onset of eczema after the age of 2 years, but the co-existence of different allergy-related diseases at 6 years was higher among those with the onset of eczema before 2 years of age.
Conclusions
Although most cases of eczema in the general population were mild to moderate, early eczema was associated with an increased risk of developing childhood asthma. These findings support the hypothesis of an atopic march in the general population.
Trial registration
The Prevention of Allergy among Children in Trondheim study has been identified as ISRCTN28090297 in the international Current Controlled Trials database
doi:10.1186/1471-2431-12-168
PMCID: PMC3532218  PMID: 23095804
Eczema; Asthma; Child; Preschool; Cohort; Questionnaires
17.  Eczema and early solid feeding in preterm infants 
Archives of Disease in Childhood  2004;89(4):309-314.
Aims: To establish whether development of eczema is influenced by feeding practices in preterm infants, while taking account of confounding factors.
Methods: Data were assembled from 257 infants born prematurely and studied to 12 months post-term. Logistic regression analysis was performed to establish the association between feeding practices and eczema, allowing for potential confounding factors including the infants' gender, parental atopic status, social background, and parental smoking habits.
Results: For the development of eczema (with or without other symptoms) by 12 months post-term, the introduction of four or more solid foods by or before 17 weeks post-term was a significant risk (odds ratio 3.49). Male infants were at significantly higher risk (odds ratio 1.84). In addition, having non-atopic parents who introduced solid foods before 10 weeks post-term or having at least one atopic parent represented a significant risk scenario (odds ratio 2.94).
Conclusions: Early introduction of a diverse range of solid foods may predispose the preterm infant to eczema development by 12 months post-term. Furthermore, non-atopic parents who practice early as opposed to late introduction of solid foods may be exposing preterm infants to a greater risk of eczema by 12 months post-term.
doi:10.1136/adc.2002.020065
PMCID: PMC1719859  PMID: 15033836
18.  Clinical study of peanut and nut allergy in 62 consecutive patients: new features and associations. 
BMJ : British Medical Journal  1996;312(7038):1074-1078.
OBJECTIVE--To investigate clinical features of acute allergic reactions to peanuts and other nuts. DESIGN--Analysis of data from consecutive patients seen by one doctor over one year in an allergy clinic at a regional referral centre. SUBJECTS--62 patients aged 11 months to 53 years seen between October 1993 and September 1994. MAIN OUTCOME MEASURES--Type and severity of allergic reactions, age at onset of symptoms, type of nut causing allergy, results of skin prick tests, and incidence of other allergic diseases and associated allergies. RESULTS--Peanuts were the commonest cause of allergy (47) followed by Brazil nut (18), almond (14), and hazelnut (13). Onset of allergic symptoms occurred by the age of 2 years in 33/60 and by the age of 7 in 55/60. Peanuts accounted for all allergies in children sensitised in the first year of life and for 82% (27/33) of allergies in children sensitised by the third year of life. Multiple allergies appeared progressively with age. The commonest symptom was facial angioedema, and the major feature accounting for life threatening reactions was laryngeal oedema. Hypotension was uncommon. Of 55 patients, 53 were atopic--that is, had positive skin results of tests to common inhaled allergens--and all 53 had other allergic disorders (asthma, rhinitis, eczema) due to several inhaled allergens and other foods. CONCLUSIONS--Sensitisation, mainly to peanuts, is occurring in very young children, and multiple peanut/nut allergies appear progressively. Peanut and nut allergy is becoming common and can cause life threatening reactions. The main danger is laryngeal oedema. Young atopic children should avoid peanuts and nuts to prevent the development of this allergy.
PMCID: PMC2350892  PMID: 8616415
19.  Tree Nut Allergy, Egg Allergy, and Asthma in Children 
Clinical pediatrics  2010;50(2):133-139.
Background
Children with food allergies often have concurrent asthma.
Objective
The authors aimed to determine the prevalence of asthma in children with food allergies and the association of specific food allergies with asthma.
Methods
Parental questionnaire data regarding food allergy, corroborated by allergic sensitization were completed for a cohort of 799 children with food allergies. Multivariate regression analysis tested the association between food allergy and reported asthma.
Results
In this cohort, the prevalence of asthma was 45.6%. After adjusting for each food allergy, environmental allergies, and family history of asthma, children with egg allergy (odds ratio [OR] = 2.0; 95% confidence interval [CI] = 1.3–3.2; P < .01) or tree nut allergy (OR = 2.0; 95% CI = 1.1–3.6; P = .02) had significantly greater odds of report of asthma.
Conclusion
There is a high prevalence of asthma in the food-allergic pediatric population. Egg and tree nut allergy are significantly associated with asthma, independent of other risk factors.
doi:10.1177/0009922810384720
PMCID: PMC3070157  PMID: 21098525
asthma; food allergy; food hypersensitivity; nut allergy; nut hypersensitivity; egg allergy; egg hypersensitivity; pediatrics; allergy; asthma epidemiology
20.  The introduction of solids in relation to asthma and eczema 
Archives of Disease in Childhood  2004;89(4):303-308.
Background: Despite scarce scientific evidence, current feeding guidelines recommend delayed introduction of solids for the prevention of asthma and allergy.
Aims: To explore whether late introduction of solids is protective against the development of asthma, eczema, and atopy.
Methods: A total of 642 children were recruited before birth and followed to the age of 5½ years. Main outcome measures were: doctor's diagnosis of eczema ever, atopy according to skin prick test results against inhalant allergens, preschool wheezing, transient wheezing, all defined at age 5–5½ years. Introduction of solids as main exposure measure was assessed retrospectively at age 1 year.
Results: There was no evidence for a protective effect of late introduction of solids for the development of preschool wheezing, transient wheezing, atopy, or eczema. On the contrary, there was a statistically significant increased risk of eczema in relation to late introduction of egg (aOR 1.6, 95% CI 1.1 to 2.4) and milk (aOR 1.7, 95% CI 1.1 to 2.5). Late introduction of egg was furthermore associated with a non-significant increased risk of preschool wheezing (aOR 1.5, 95% CI 0.92 to 2.4). There was no statistical evidence of feeding practices playing a different role in the development of asthma and eczema after stratification for parental asthma and atopy status.
Conclusions: Results do not support the recommendations given by present feeding guidelines stating that a delayed introduction of solids is protective against the development of asthma and allergy.
doi:10.1136/adc.2002.025353
PMCID: PMC1719882  PMID: 15033835
21.  TREATMENT OF ASTHMA AND FOOD ALLERGY WITH HERBAL INTERVENTIONS FROM TRADITIONAL CHINESE MEDICINE 
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 high prevalence of anxiety in particular 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 (TCM), used in Asia for centuries, is beginning to play a role in Western health care. There is increasing scientific evidence supporting the use of TCM for asthma treatment.
This review article discusses promising TCM interventions for asthma, food allergy and comorbid conditions and explores their possible mechanisms of action. Since 2005, several controlled clinical studies of “anti-asthma” herbal remedies have been published. Among the herbal medicines, anti-asthma herbal medicine intervention (ASHMI) is the only anti-asthma TCM product that is a US FDA investigational new drug (IND) that has entered clinical trials. Research into ASHMI’s effects and mechanisms of actions in animal models is actively being pursued. Research on TCM herbal medicines for treating food allergy is rare. The herbal intervention, Food Allergy Herbal Formula-2 (FAHF-2) is the only US FDA botanical IND under investigation as a multiple food allergy therapy. Published articles and abstracts, as well as new data generated in preclinical and clinical studies of ASHMI and FAHF-2 are the bases for this review. The effect of TCM therapy on food allergy associated recalcitrant eczema, based on case review, is also included.
Laboratory and clinical studies demonstrate a beneficial effect of ASHMI treatment on asthma. The possible mechanisms underlying the efficacy are multiple. Preclinical studies demonstrated the efficacy and safety of FAHF-2 for treating food allergy in a murine model. A clinical study demonstrated that FAHF-2 is safe, well tolerated, and exhibited beneficial immunomodulatory effects. A clinical report showed that TCM treatment reduced eczema scores and improved quality of life. Herbal interventions, ASHMI and FAHF-2 may be further developed as botanical drugs for treating asthma and food allergy. TCM may also be of benefit for comorbid conditions such as anxiety and recalcitrant eczema. More controlled studies are warranted.
In conclusion, novel approaches for treatment of asthma and food allergy and comorbid conditions such as anxiety and eczema are urgently needed. This article discusses promising interventions for such conditions from traditional Chinese medicine (TCM) and explores their possible mechanisms of action.
doi:10.1002/msj.20294
PMCID: PMC4118473  PMID: 21913200
Herbal interventions; traditional Chinese medicine; ASHMI; FAHF-2; asthma; food allergy
22.  Endotoxin Exposure and Eczema in the First Year of Life 
Pediatrics  2004;114(1):13-18.
Objective
Exposure to endotoxin in early life has been proposed as a factor that may protect against the development of allergic diseases such as eczema. The objective of this study was to examine the relation between endotoxin exposure in early life and eczema in the first year of life in children with parental history of asthma or allergies.
Methods
This study used a prospective birth cohort study of 498 children who had a history of allergy or asthma in at least 1 parent and lived in metropolitan Boston. A subset of 401 living rooms had house dust samples adequate for analysis of endotoxin.
Results
In multivariate analyses adjusting for gender, income, and season of birth, endotoxin levels in the living room at 2 to 3 months of age was inversely associated with physician- or nurse-diagnosed eczema in the first year of life (odds ratio [OR] for each quartile increment: 0.76; 95% confidence interval [CI]: 0.61–0.96). Exposure to a dog in the home at age 2 to 3 months was also inversely associated with eczema in the first year of life, but the CI widened when endotoxin was included in the multivariate model (OR: 0.54; 95% CI: 0.27–1.09). Other variables associated with eczema in the first year of life included paternal history of eczema (OR: 1.91; 95% CI: 1.03–3.55) and maternal specific immunoglobulin E positivity to ≥1 allergen (OR: 1.61; 95% CI: 1.01–2.56).
Conclusions
Among children with parental history of asthma or allergies, exposure to high levels of endotoxin in early life may be protective against eczema in the first year of life. In these children, paternal history of eczema and maternal sensitization to at least 1 allergen are associated with an increased risk of eczema in the first year of life.
PMCID: PMC1242194  PMID: 15231902
Ig, immunoglobulin; OR, odds ratio; CI, confidence interval; Th2, T-helper cell type 2
23.  Prevalence, incidence and predictive factors for hand eczema in young adults – a follow-up study 
BMC Dermatology  2013;13:14.
Background
Hand eczema is common in the general population and affects women twice as often as men. It is also the most frequent occupational skin disease. The economic consequences are considerable for society and for the affected individuals.
Methods
To investigate the prevalence and incidence of hand eczema and to evaluate risk factors for development of hand eczema in young adults. Subjects and methods; This is a prospective follow-up study of 2,403 young adults, 16 – 19 years old in 1995 and aged 29 – 32 years, 13 years later, in 2008. They completed a postal questionnaire that included questions regarding one-year prevalence of hand eczema, childhood eczema, asthma, rhino-conjunctivitis and factors considered to affect hand eczema such as hand-washing, washing and cleaning, cooking, taking care of small children and usage of moisturisers. These factors were evaluated with the multinominal logistic regression analysis.
Results
The one-year prevalence of hand eczema was 15.8% (females 20.3% and males 10.0%, p < 0.001). The incidence was 11.6 cases per 1000 person-years (females 14.3 and males 5.2, p < 0.001). Childhood eczema was the most important risk factor for hand eczema. The odds ratios were 13.17 when having hand eczema 1995 and 2008 compared to 5.17 in 2008 (p < 0.001). A high frequency of hand washing was important in predicting hand eczema only when having 1-year prevalence 2008, OR 1.02 (p = 0.038).
Conclusions
After 13 years an increased 1-year prevalence of hand eczema was found. The significant risk factors for hand eczema changed over time from endogenous to exogenous factors.
doi:10.1186/1471-5945-13-14
PMCID: PMC3819704  PMID: 24164871
Hand eczema; Childhood eczema; Prevalence; Incidence; Cohort; Gender; Skin care; Hand-wash
24.  429 Natural History of Food Allergy in Childhood -3 Years' Follow up of Pediatric Food Allergy Patients 
Background
Food allergy (FA) is prevalent among children however natural history of FA is not fully clarified.
Methods
We sought to investigate the natural course of childhood FA. To follow up the transition of same patients, we collected clinical records of patients with 3 years’ interval from 2008 to 2010. Four hundred ninety-one patients (male 321 and female 170) were recruited to this study.
Results
The onset of FA was at the age of 5 months ± 1 year 3 month (mean ± SD). The clinical type at the onset was with infantile atopic eczema (84.1%), and followed by immediate reactions without eczema (14.9%). The initial diagnosis age was 10 months ± 1 year 4 months, and the first visit to our department was 1 year 11 month ± 2 years 5 months. Current age of the patients was 7 years 5 months ± 2 years 11 months, and 444 patients (90.4%) had experienced immediate reactions. The number of eliminated foods decreased from 2.4 ± 1.5 items/patient (n = 1191) to 1.9 ± 1.6 items/patient (n = 926) in 3 years. The ratio of stopping elimination of major allergens was 35.9% (121/337 patients) for hen's egg, 25.6% (52/203 patients) for cow's milk and 47.8% (44/92 patients) for wheat. Fourteen patients (2.9%) had developed new food allergies, and 2 of them had experienced anaphylaxis by tree nuts. Newly diagnosed allergens were only 0.1 ± 0.3 items/patient (n = 32), and nuts (n = 6) and peanut (n = 5) were the most frequent. Seventy-nine patients (16.1%) had developed complete remission of FA in 3 years, and 21.5% of them (17 patients) had never developed immediate reactions.
Conclusions
Most of pediatric FA started during infancy with atopic eczema, and developing tolerance is expected with aging. In some patients, persistent FA is troublesome for school age children.
doi:10.1097/01.WOX.0000412192.55876.a1
PMCID: PMC3513182
25.  Eczema (atopic) 
Clinical Evidence  2006;2006:1716.
Introduction
Atopic eczema affects 15-20% of schoolchildren worldwide and 2-10% of adults. Only about 60% of people with eczema demonstrate atopy, with specific immunoglobulin E responses to allergens.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of self-care treatments, topical medical treatments, and dietary interventions in adults and children with established atopic eczema? What are the effects of breast feeding as a primary preventive intervention in predisposed infants? What are the effects of reducing allergens as a primary preventive intervention in predisposed infants? We searched: Medline, Embase, The Cochrane Library and other important databases up to September 2006 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 33 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: breast feeding, controlling house dust mites, corticosteroids, dietary exclusion of eggs or cows' milk, elemental diets, emollients, essential fatty oils, few-foods diet, multivitamins, pimecrolimus, probiotics, pyridoxine, reducing maternal dietary allergens, tacrolimus, vitamin E, and zinc supplements.
Key Points
Atopic eczema affects 15-20% of schoolchildren worldwide and 2-10% of adults. Only about 60% of people with eczema demonstrate atopy, with specific immunoglobulin E responses to allergens. Remission occurs in two thirds of children by the age of 15 years, but relapses may occur later.
There is a consensus that emollients are effective for treating the symptoms of atopic eczema, although little high quality research has been done to confirm this.
Corticosteroids improve clearance of lesions and decrease relapse rates compared with placebo, although we don't know which is the most effective corticosteroid or dosing regimen. Topical corticosteroids seem to have few adverse effects, but may cause burning, skin thinning and telangiectasia, especially in children.
Pimecrolimus and tacrolimus improve clearance of lesions compared with placebo and may have a role in people with a high risk of corticosteroid adverse effects.
CAUTION: An association has been suggested between pimecrolimus and tacrolimus and skin cancer. They should be used only where other treatments have failed.
We don't know whether vitamin E, pyridoxine, zinc supplementation, exclusion or elemental diets or probiotics reduce symptoms in atopic eczema, as there are insufficient good quality studies. Essential fatty acids such as evening primrose oil, blackcurrant seed oil or fish oil do not seem to reduce symptoms in atopic eczema.
We don't know whether prolonged breast feeding, reducing maternal dietary allergens, or control of house dust mites, can prevent the development of atopic eczema in children. Early introduction of probiotics in the last trimester of pregnancy and during breastfeeding may reduce the risk of atopic eczema in the baby.
PMCID: PMC2907628

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