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1.  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
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.
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
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
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)
PMCID: PMC3949681  PMID: 24618794
2.  The effects of elimination diet on nutritional status in subjects with atopic dermatitis 
Nutrition Research and Practice  2013;7(6):488-494.
A food allergy is an adverse health effect arising from a specific immune response that occurs reproducibly upon exposure to a given food. In those with food allergies that are thought to cause aggravation of eczema, food avoidance is important. The objective of this study was to research the nutritional status of patients with food allergies. A total of 225 subjects diagnosed with atopic dermatitis underwent a skin prick test as well as measurement of serum immunoglobulin E. Food challenge tests were conducted using seven food items: milk, eggs, wheat, soybeans, beef, pork, and chicken. At post-food challenge visits to the test clinic, participants completed a three-day dietary record, which included two week days and one weekend day, in order to evaluate energy intake and diet quality during the challenge. We analyzed nutrient intake based on differential food allergens. Subjects with a food allergy to milk showed lower intake of Ca, Zn, and vitamin B2, and subjects with a food allergy to egg showed lower intake of vitamin A, B1, B2, niacin, and cholesterol. Subjects with a food allergy to wheat and soybean showed lower intake of Ca, P, Fe, K, Zn, vitamin B2, vitamin B6, and niacin; and subjects with a food allergy to beef, pork, and chicken showed lower intake of Fe and higher intake of K, vitamin A, B2. Subjects with atopic dermatitis were lacking in several nutrients, including vitamin A and vitamin C. A greater number of food allergies showed an association with a greater number of nutrient intake deficiencies. Allergen avoidance is the basic treatment for atopic dermatitis. However, when the allergen is food, excessive restriction can lead to nutrition deficiency. Findings of this study suggest the necessity for enhanced nutritional education in order to provide substitute foods for patients with food allergies who practice food restriction.
PMCID: PMC3865272  PMID: 24353835
Food allergy; atopic dermatitis; food restriction
3.  Food allergies in developing and emerging economies: need for comprehensive data on prevalence rates 
Although much is known today about the prevalence of food allergy in the developed world, there are serious knowledge gaps about the prevalence rates of food allergy in developing countries. Food allergy affects up to 6% of children and 4% of adults. Symptoms include urticaria, gastrointestinal distress, failure to thrive, anaphylaxis and even death. There are over 170 foods known to provoke allergic reactions. Of these, the most common foods responsible for inducing 90% of reported allergic reactions are peanuts, milk, eggs, wheat, nuts (e.g., hazelnuts, walnuts, almonds, cashews, pecans, etc.), soybeans, fish, crustaceans and shellfish. Current assumptions are that prevalence rates are lower in developing countries and emerging economies such as China, Brazil and India which raises questions about potential health impacts should the assumptions not be supported by evidence. As the health and social burden of food allergy can be significant, national and international efforts focusing on food security, food safety, food quality and dietary diversity need to pay special attention to the role of food allergy in order to avoid marginalization of sub-populations in the community. More importantly, as the major food sources used in international food aid programs are frequently priority allergens (e.g., peanut, milk, eggs, soybean, fish, wheat), and due to the similarities between food allergy and some malnutrition symptoms, it will be increasingly important to understand and assess the interplay between food allergy and nutrition in order to protect and identify appropriate sources of foods for sensitized sub-populations especially in economically disadvantaged countries and communities.
PMCID: PMC3551706  PMID: 23256652
Food allergy; Food hypersensitivity; Nutrition; Developing countries
4.  Impairing oral tolerance promotes allergy and anaphylaxis: A new murine food allergy model 
Food allergy is a disorder in which antigenic food proteins elicit immune responses. Animal models of food allergy have several limitations that influence their utility, including failure to recapitulate several key immunologic hallmarks. Consequently, little is known regarding the pathogenesis and mechanisms leading to food allergy. Staphylococcus aureus–derived enterotoxins, a common cause of food contamination, are associated with antigen responses in atopic dermatitis.
We hypothesized that S aureus–derived enterotoxins might influence the development of food allergy. We examined the influence of administration of staphylococcal enterotoxin B (SEB) with food allergens on immunologic responses and compared these responses with those elicited by a cholera toxin–driven food allergy model.
Oral administration of ovalbumin or whole peanut extract with or without SEB was performed once weekly. After 8 weeks, mice were challenged with oral antigen alone, and the physiologic and immunologic responses to antigen were studied.
SEB administered with antigen resulted in immune responses to the antigen. Responses were highly TH2 polarized, and oral challenge with antigen triggered anaphylaxis and local and systemic mast cell degranulation. SEB-driven sensitization induced eosinophilia in the blood and intestinal tissues not observed with cholera toxin sensitization. SEB impaired tolerance specifically by impairing expression of TGF-b and regulatory T cells, and tolerance was restored with high-dose antigen.
We demonstrate a new model of food allergy to oral antigen in common laboratory strains of mice that recapitulates many features of clinical food allergy that are not seen in other models. We demonstrate that SEB impairs oral tolerance and permits allergic responses.
PMCID: PMC2787105  PMID: 19022495
Food allergy; Staphylococcus aureus enterotoxin B; TH2; anaphylaxis; murine; peanut; ovalbumin; tolerance; mast cells; eosinophils
5.  Manifestations of food protein induced gastrointestinal allergies presenting to a single tertiary paediatric gastroenterology unit 
Food protein induced gastrointestinal allergies are difficult to characterise due to the delayed nature of this allergy and absence of simple diagnostic tests. Diagnosis is based on an allergy focused history which can be challenging and often yields ambiguous results. We therefore set out to describe a group of children with this delayed type allergy, to provide an overview on typical profile, symptoms and management strategies.
This retrospective analysis was performed at Great Ormond Street Children’s Hospital. Medical notes were included from 2002 – 2009 where a documented medical diagnosis of food protein induced gastrointestinal allergies was confirmed by an elimination diet with resolution of symptoms, followed by reintroduction with reoccurrence of symptoms. Age of onset of symptoms, diagnosis, current elimination diets and food elimination at time of diagnosis and co-morbidities were collected and parents were phoned again at the time of data collection to ascertain current allergy status.
Data from 437 children were analysis. The majority (67.7%) of children had an atopic family history and 41.5% had atopic dermatitis at an early age. The most common diagnosis included, non-IgE mediated gastrointestinal food allergy (n = 189) and allergic enterocolitis (n = 154) with symptoms of: vomiting (57.8%), back-arching and screaming (50%), constipation (44.6%), diarrhoea (81%), abdominal pain (89.9%), abdominal bloating (73.9%) and rectal bleeding (38.5%). The majority of patients were initially managed with a milk, soy, egg and wheat free diet (41.7%). At a median age of 8 years, 24.7% of children still required to eliminate some of the food allergens.
This large retrospective study on children with food induced gastrointestinal allergies highlights the variety of symptoms and treatment modalities used in these children. However, further prospective studies are required in this area of food allergy.
PMCID: PMC3828665  PMID: 23919257
6.  Referrals to a regional allergy clinic - an eleven year audit 
BMC Public Health  2010;10:790.
Allergy is a serious and apparently increasing public health problem yet relatively little is known about the types of allergy seen in routine tertiary practice, including their spatial distribution, co-occurrence or referral patterns. This study reviewed referrals over an eleven year period to a regional allergy clinic that had a well defined geographical boundary. For those patients confirmed as having an allergy we explored: (i) differences over time and by demographics, (ii) types of allergy, (iii) co-occurrence, and (iv) spatial distributions.
Data were extracted from consultant letters to GPs, from September 1998 to September 2009, for patients confirmed as having an allergy. Other data included referral statistics and population data by postcode. Simple descriptive analysis was used to describe types of allergy. We calculated 11 year standardised morbidity ratios for postcode districts and checked for spatial clustering. We present maps showing 11 year rates by postcode, and 'difference' maps which try to separate referral effect from possible environmental effect.
Of 5778 referrals, 961 patients were diagnosed with an allergy. These were referred by a total of 672 different GPs. There were marked differences in referral patterns between GP practices and also individual GPs. The mean age of patients was 35 and there were considerably more females (65%) than males. Airborne allergies were the most frequent (623), and there were very high rates of co-occurrence of pollen, house dust mite, and animal hair allergies. Less than half (410) patients had a food allergy, with nuts, fruit, and seafood being the most common allergens. Fifteen percent (142) had both a food and a non-food allergy. Certain food allergies were more likely to co-occur, for example, patients allergic to dairy products were more likely to be allergic to egg.
There were age differences by types of allergy; people referred with food allergies were on average 5 years younger than those with other allergies, and those allergic to nuts were much younger (26 Vs 38) than those with other food allergies.
There was clear evidence for spatial clustering with marked clustering around the referral hospital. However, the geographical distribution varied between allergies; airborne (particularly pollen allergies) clustered in North Dartmoor and Exmoor, food allergies (particularly nut allergies) in the South Hams, and on small numbers, some indication of seafood allergy in the far south west of Cornwall and in the Padstow area.
This study shows marked geographical differences in allergy referrals which are likely to reflect a combination of environmental factors and GP referral patterns. The data suggest that GPs may benefit from education and ongoing decision support and be supported by public education on the nature of allergy. It suggests further research into what happens to patients with allergy where there has been low use of tertiary services and further research into cross-reactivity and co-occurrence, and spatial distribution of allergy.
PMCID: PMC3022859  PMID: 21190546
7.  Impact of primary food allergies on the introduction of other foods amongst Canadian children and their siblings 
Food-allergic children frequently avoid other highly allergenic foods. The NIAID 2010 guidelines state that individuals with an IgE-mediated food allergy should avoid their specific allergens and physicians should help patients to decide whether certain cross-reactive foods also should be avoided. Patients at risk for developing food allergy do not need to limit exposure to foods that may be cross-reactive with the major food allergens. The purpose of this study was to determine if parents of food-allergic children are given advice regarding introduction of allergenic foods; if these foods are avoided or delayed; if there is anxiety when introducing new foods; and if introducing other allergenic foods leads to any allergic reaction. The study also determined if there was a similar pattern seen amongst younger siblings.
An online survey was administered between December 2011 and March 2012 via Anaphylaxis Canada’s website, available to Canadian parents and caregivers who are registered members of the organization and who have a child with a food allergy.
644 parents completed the online survey. 51% of families were given advice regarding the introduction of other allergenic foods. 72% were told to avoid certain foods, and 41% to delay certain foods. 58% of parents did avoid or delay other highly allergenic foods, mainly due to a fear of allergic reaction. 69% of children did not have an allergic reaction when these foods were subsequently introduced. 68% of parents felt moderate or high levels of anxiety when introducing other foods. A similar pattern was seen amongst the younger siblings.
Canadian parents and caregivers of children with food allergies receive varied advice from health care professionals regarding the introduction of new allergenic foods, and feel moderate to high levels of anxiety. A similar pattern may be seen amongst younger siblings. While the majority of children in our study did not have an allergic reaction to a new food, a significant proportion of children did react. A more consistent approach to the advice given by health care professionals may decrease parental anxiety. Further research to support the 2010 NIAID guidelines may be necessary to clarify recommendations.
PMCID: PMC4063690  PMID: 24949023
Food allergy; Siblings; Food introduction; Anxiety
8.  Variably severe systemic allergic reactions after consuming foods with unlabelled lupin flour: a case series 
Lupin allergy remains a significant cause of food-induced allergic reactivity and anaphylaxis. Previous work suggests a strong association with legume allergy and peanut allergy in particular. Both doctors and the public have little awareness of lupin as an allergen.
Case presentation
Case 1 was a 41-year-old Caucasian woman without previous atopy who developed facial swelling, widespread urticaria with asthma and hypotension within minutes of eating a quiche. Her lupin allergy was confirmed by both blood and skin tests. Her lupin sensitivity was so severe that even the miniscule amount of lupin allergen in the skin testing reagent produced a mild reaction.
Case 2 was a 42-year-old mildly atopic Caucasian woman with three episodes of worsening urticaria and asthma symptoms over 6 years occurring after the consumption of foods containing lupin flour. Blood and skin tests were positive for lupin allergy.
Case 3 was a 38-year-old Caucasian woman with known oral allergy syndrome who had two reactions associated with urticaria and vomiting after consuming foods containing lupin flour. Skin testing confirmed significant responses to a lupin flour extract and to one of the foods inducing her reaction.
Case 4 was a 54-year-old mildly atopic Caucasian woman with a 7 year history of three to four episodes each year of unpredictable oral tingling followed by urticaria after consuming a variety of foods. The most recent episode had been associated with vomiting. She had developed oral tingling with lentil and chickpeas over the previous year. Skin and blood tests confirmed lupin allergy with associated sensitivity to several legumes.
Lupin allergy can occur for the first time in adults without previous atopy or legume sensitivity. Although asymptomatic sensitisation is frequent, clinical reactivity can vary in severity from severe anaphylaxis to urticaria and vomiting. Lupin allergy may be confirmed by skin and specific immunoglobulin E estimation. Even skin testing can cause symptoms in some highly sensitive individuals. The diagnosis of lupin allergy in adults may be difficult because it is frequently included as an undeclared ingredient. Better food labelling and medical awareness of lupin as a cause of serious allergic reactions is suggested.
PMCID: PMC3943371  PMID: 24529316
Anaphylaxis; Food labelling; Gluten-free spaghetti; Lupin allergy; Oral allergy
9.  Cow’s milk allergy: evidence-based diagnosis and management for the practitioner 
European Journal of Pediatrics  2014;174:141-150.
This review summarizes current evidence and recommendations regarding cow’s milk allergy (CMA), the most common food allergy in young children, for the primary and secondary care providers. The diagnostic approach includes performing a medical history, physical examination, diagnostic elimination diets, skin prick tests, specific IgE measurements, and oral food challenges. Strict avoidance of the offending allergen is the only therapeutic option. Oral immunotherapy is being studied, but it is not yet recommended for routine clinical practice. For primary prevention of allergy, exclusive breastfeeding for at least 4 months and up to 6 months is desirable. Infants with a documented hereditary risk of allergy (i.e., an affected parent and/or sibling) who cannot be breastfed exclusively should receive a formula with confirmed reduced allergenicity, i.e., a partially or extensively hydrolyzed formula, as a means of preventing allergic reactions, primarily atopic dermatitis. Avoidance or delayed introduction of solid foods beyond 4–6 months for allergy prevention is not recommended.
Conclusion: For all of those involved in taking care of children’s health, it is important to understand the multifaceted aspects of CMA, such as its epidemiology, presentation, diagnosis, and dietary management, as well as its primary prevention.
PMCID: PMC4298661  PMID: 25257836
Allergy; Children; Infants; Pediatrics
10.  496 Cross Sectional Study of 1,822 Pediatric Food Allergy Patients 
The World Allergy Organization Journal  2012;5(Suppl 2):S174-S175.
The aim of this study is to clarify the cross section of pediatric food allergy patients. We investigated the profiles of food allergy (FA) patients seen in our department.
The number of food allergy patients seen in our department from January to December in 2010 was a total of 1,822 (male: 1207, female: 615, mean age: 5.8 ± 3.8 year). We collected and analyzed the clinical information of these patients from our medical record. We obtained information on the age of FA onset & FA diagnosis, clinical types of FA at the onset, causative food allergens, other allergic complications, and application of oral immunotherapy (OIT).
The average age of FA onset was 8 months, and that of diagnosis was 1 year old, respectively. The most common clinical types of FA at the time of onset were infantile atopic dermatitis (AD) type with food allergy (66.4%) followed by immediate type (30.8%). Food allergens avoided by the patients were the total number of 4,203 items (2.1 items as average). The most common eliminated food was hen's egg (1,245 cases; 29.6%), followed by cow's milk (786 cases; 18.7%), peanut (449 cases; 10.7%), and wheat (407 cases; 9.7%). Food-dependent exercise-induced anaphylaxis (FDEIA) was the total of 18 cases, and the most common causative food for FDEIA was wheat (10 cases) followed by peach (4 cases). One hundred and seventy five cases (9.6%) were currently receiving OIT. Main causative foods under OIT were hen's egg (63 cases), cow's milk (80 cases), and wheat (30 cases). The average starting age of OIT was 7.1 years old. Regarding complications of allergic diseases other than FA, 1119 (61.4%) had atopic dermatitis, and 541 (29.7%) bronchial asthma.
We were able to clarify the cross section of food allergy patients in our department and to obtain the basic data to follow continuous transition of these patients.
PMCID: PMC3512856
11.  365 Patch Testing Results in Contact Dermatitis from the Allergist's Perspective 
Contact Dermatitis (CD) is a frequently encountered skin disease by allergists and dermatologists that results from contact with external allergens. Patch Testing (PT) remains the gold standard in the diagnosis of allergic CD. Studies evaluating PT from allergy practices are lacking.
A multi-center, retrospective chart review of PT within the last 5 years at allergy practices in 3 institutions. We report PT results using allergens in the Thin-Layer Rapid-Use Epicutaneous Test (TT) and additional supplemental allergens [North American Contact Dermatitis (NACD) Panel, Dormer Cosmetic Panel, hairdresser's panel, corticosteroid panel and personal products]. Additionally, patient characteristics including age, gender, occupation, dermatitis site, history of atopic disease and final diagnosis were also obtained.
A total of 427 patients (mean age = 49.8 years) were patch tested, 82% were female, 54% reported an atopic history (history of asthma, atopic dermatitis, allergic rhinitis or food allergy), 30% were tested with TT, 60% with NACD panel, 30% with cosmetic series, 15% with corticosteroid series and 35% with personal products. The 5 most common positive PT allergens were nickel sulfate, fragrance mix I, P-phenylenediamine, thimerosal and cobalt chloride. The most common dermatitis sites were eyelid/periorbital (31%), facial (25%) and trunk (21%). 56.9% of patients were positive to at least one TT allergen. 25.6% of patients were positive to both a TT and a supplemental allergen (these patients would have been “partially evaluated” with TT allergens alone as they are positive to at least 1 TT allergen and 1 supplemental allergen). 12.5% of patients were negative to a TT allergen and positive to at least 1 supplemental allergen only (these patients would have been “missed” as they are negative to all TT allergens, but positive to at least 1 supplemental allergen).
Nickel remains the most common allergen. When evaluating patients with CD, testing with TT allergens alone would miss 12.5% of patients while 25.6% of patients would be only partially evaluated. As half of our patients were positive to at least 1 TT allergen, the TT remains an adequate screening tool but a more comprehensive panel may be needed to fully evaluate contact dermatitis.
PMCID: PMC3513026
12.  Food allergy 
Food allergy is defined as an adverse immunologic response to a dietary protein. Food-related reactions are associated with a broad array of signs and symptoms that may involve many bodily systems including the skin, gastrointestinal and respiratory tracts, and cardiovascular system. Food allergy is a leading cause of anaphylaxis and, therefore, referral to an allergist for appropriate and timely diagnosis and treatment is imperative. Diagnosis involves a careful history and diagnostic tests, such as skin prick testing, serum-specific immunoglobulin E (IgE) testing and, if indicated, oral food challenges. Once the diagnosis of food allergy is confirmed, strict elimination of the offending food allergen from the diet is generally necessary. For patients with significant systemic symptoms, the treatment of choice is epinephrine administered by intramuscular injection into the lateral thigh. Although most children “outgrow” allergies to milk, egg, soy and wheat, allergies to peanut, tree nuts, fish and shellfish are often lifelong. This article provides an overview of the epidemiology, pathophysiology, diagnosis, management and prognosis of patients with food allergy.
PMCID: PMC3245440  PMID: 22166142
13.  Food Allergy--Lessons from Asia 
This is a review on published data available on food allergy in East Asia and a discussion on the insights that it offers.
PubMed searches were made for terms food allergy and anaphylaxis, in combination with Asia.
There is a paucity of population-based prevalence studies on food allergy in Asia. Certain unique food allergens, such as buckwheat, chestnuts, chickpeas, bird's nest, and royal jelly, which are consumed extensively by certain Asian populations have resulted in clinical food allergy of little importance in other populations. Crustacean shellfish is of importance in this region relative to other common food allergens. The high consumption of these foods and possibly coupled with cross-reactive tropomyosins from dominant inhalant dust mite and cockroach allergens in this region may explain this phenomenon. In contrast, the prevalence of peanut allergy is relatively low in this region. The reasons for this difference are not apparent. However, this may be a reflection of the general reduced propensity in this region to allergic diseases as seen with asthma.
Further research on food allergy in Asia is warranted because it offers unique opportunities to further our understanding on the influence of population and environment.
PMCID: PMC3650988  PMID: 23282480
food allergy; Asia; shellfish allergy; peanut allergy; buckwheat; bird's nest; chickpeas; royal jelly
14.  Prevalence of Allergies among University Students: A Study from Ajman, United Arab Emirates 
ISRN Allergy  2014;2014:502052.
Aim. Urbanization and globalization in the Middle East have resulted in drastic environmental changes and increased allergens present in the environment. This study aimed to assess the prevalence of allergies among undergraduate students from a university. Material and Methods. This cross-sectional survey was carried out among undergraduate students of a University at Ajman, UAE. A self-administered questionnaire was used as research instrument for data collection. The demographic data and the allergy characteristics were collected and analyzed using SPSS version 19. Descriptive and inferential statistics were performed. Results. A total of 255 students (33.3% males; 66.7% females) were included. Commonest allergies among the students were allergic conjunctivitis (104 (40.8%)), allergic dermatitis (89 (34.9%)), and eczema (38 (14.9%)). Family history of allergies was strongly associated with occurrence of allergic conjunctivitis and allergic dermatitis. In about 58 (22%) of the students, dust was the most common triggering factor for allergies. Allergies associated with pollen, food, and drugs were less frequent. The distribution of allergies based on gender revealed female preponderance in all types of allergies. Students with allergies reported interference with their daily activities, and academic, social, and extracurricular activities. Conclusions. Allergic conjunctivitis and allergic dermatitis were the frequent allergies reported. Adequate preventive strategies can crumb the prevalence of allergies.
PMCID: PMC3950405  PMID: 24701360
15.  434 Frequency of Food-sensitization by Prick-to-Prick Test and Atopy Patch Test in Allergic Children 
Food-allergy is a substantial and evolving health issue. We evaluate the frequency of food sensitization by prick-to-prick and atopy patch test (APT) in allergic children in a tertiary pediatric care center.
Cross-sectional retrospective study of prick-to-prick and APT tests made in atopic children attending to the Pediatric Allergy and Clinical Immunology outpatient clinic aged 6 months to 19 years. Patients were stratified in 4 groups according to age (<1, 1–5, 6–10 and >11 years), and by atopy-related diagnosis (asthma, rhinitis, food allergy, atopic dermatitis and eosinophilic gastroenteropathy).
Total of 170 prick-to-prick with fresh foods were made, 135 were positive with the next distribution: milk 28.8%, (95% CI, 21.3-36.3%), egg white 20.1% (95% CI, 13.5-26.8%), banana 19.4% (95% CI, 12.8-26%). Sensitization to milk was most common in children aged 1 to 5 years old with 26.9% (95% CI, 17.1-36.8%) compared with corn, nuts and peanuts P < 0.05. Sensitization to milk was the most frequent in the food allergy diagnosis group with 27.1% (95% CI,15.8-38.5%) compared with wheat, corn and peanuts P < 0.05.
A total of 140 APT tests were made, 105 were positive with the next distribution: soybeans 53.3% (95% CI,43.8-62.8%), peanut and chocolate both with 50.5% (95% CI,40.9-60,.0). This finding was sustained in patients with atopic dermatitis with soybean 55.6% (95% CI,36.8-74.3) compared to egg yolk. Sensitization to soybeans was most common in children aged 1 to 5 years old with 52.1% (95% CI,40.6-63.6) compared to rice and egg yolk P < 0.05. A different distribution was found for the 6 to 10 years old aged group: peanut 41.9% (95% CI,27.1-56.6) compared with egg yolk P < 0.05.
Milk is the most common food-allergen found by prick-to-prick in children independent of age or allergic diagnosis, with statistical significant difference, when compared to other food-allergens, in the group of food-allergy diagnosis and in the 1 to 5 years old age-group. Soybean is the most common food-allergen found in atopy patch test in the groups <1, 1 to 5 and >11 years old, independent of atopy related diagnosis, with statistical significant difference, when compared to other food-allergens in the group of atopic dermatitis and in the 1 to 5 years old age-group. For the 6 to 10 years old group peanut was the most common food-allergen found by APT, independent of atopy related diagnosis
PMCID: PMC3513170
16.  435 Increasing Incidence of Food Allergy in Zimbabwe 
The World Allergy Organization Journal  2012;5(Suppl 2):S155-S156.
Data relating to allergic diseases in general and food allergies in particular in the Central African region is scant. Despite observations by the ISAAC studies that airborne allergen sources were common, little has been reported about food allergens. We reviewed data from our laboratory and outpatient records of patients consulted to estimate the magnitude of the disease in our population.
Patients attending the only specialist allergy diagnostic facility in the country (Asthma, Allergy and Immune Dysfunction Clinic) were offered semi-quantitative allergen specific IgE antibody determination as part of their diagnostic work-up. Alongside skin-prick testing, the Euroimmun immunoblots were used to establish IgE reactivity to a variety of allergen sources.
Six hundred thirty five patients were enrolled between January 2009 and April 2011. These were born between 1931 and 2010. IgE reactivity to egg, codfish, cows milk, wheat flour, rice, soya bean, peanut, hazelnut, carrot, potato and apple was investigated using the immunoblot technique. Results were scored negative or positive. The grades of positive were weak (±), low (+), moderate (++) and high (+++). Overall, 47% of the patients reacted to one or multiple allergen sources. Across the age spectrum, allergen specific IgE reactivity was most frequent against potato (16%) and peanut (15%) and lowest against milk (2.7%) and codfish (2.7%), others were intermediate. Egg white reactivity was highest in those below the age of 5 years (7%). IgE reactivity in patients born before 1959 was less than 1%. This increased to 3.4%, 4.8% and 64% respectively in those born before 1969, 1979 and 1989. Nineteen (19%) of patients born in 1990 to 1999 were reactive to a variety of food allergen sources. Likewise, 12% of those born between 2000 and 2011 were reactive. Food allergen reactivity paralleled inhalant allergen source sensitisation in all age groups.
In this sample of symptomatic patients we have shown that allergen specific IgE reactivity to dietary sources was high. An exponential increase in IgE reactivity in patients born between 1990 and 2011 was a surprising observation. Possible explanations include urbanisation, life-style and dietary changes in this predominantly urban population. The results call for a systematic investigation of the predisposing factors.
PMCID: PMC3512812
17.  Management of the Patient with Multiple Food Allergies 
Food allergies affect 6% of children and 3% to 4% of adults in the United States. Although several studies have examined the prevalence of food allergy, little information is available regarding the prevalence of multiple food allergies. Estimates of prevalence of people allergic to multiple foods is difficult to ascertain because those with allergy to one food may avoid additional foods for concerns related to cross-reactivity, positive tests, or prior reactions, or they may be reluctant to introduce foods known to be common allergens. Diagnosis relies on an accurate history and selective IgE testing. It is important to understand the limitations of the available tests and the role of cross-reactivity between allergens. Allergen avoidance and readily accessible emergency medications are the cornerstones of management. In addition, a multidisciplinary approach to management of individuals with multiple food allergies may be needed, as avoidance of several food groups can have nutritional, developmental, and psychosocial consequences.
PMCID: PMC3071637  PMID: 20431971
Multiple food allergy; IgE; Sensitization; Cross-reactivity; Diagnosis; Allergy management
18.  422 A Rare Case of Food-induced Anaphylaxis to Pink Peppercorns 
The incidence and prevalence of food allergies appear to be on the rise over the past 20 years. The most common foods to produce an IgE mediated hypersensitivity reaction in adults include peanut, tree nuts, and seafood. The increased use of spices in the U.S. has resulted in a growing number of patients presenting with hypersensitivity reactions.
We report a case of a 26 year-old-female who developed anaphylaxis after ingesting pink peppercorn seasoning. The patient was diagnosed with a tree nut allergy at 18 years of age when she developed hives, vomiting and throat closure after ingesting cashews. More recently, she had 3 similar anaphylactic episodes requiring epinephrine and emergency room care when she unknowingly consumed tree nuts contained in foods while dining out (veggie burger, pesto sauce, almonds in Indian food). She again had similar symptoms while eating a home prepared meal in which tree nuts were not included. Intramuscular epinephrine was administered and she was subsequently treated with oral steroids and antihistamines. It was later determined that a new peppercorn medley with pink peppercorns was used for seasoning. The reaction did not occur when she ate the same meal without pink peppercorn seasoning. Food specific IgE testing revealed an elevated IgE for cashews (2.52 kUA/L) and pistachios (2.85 kUA/L).
Pink peppercorn is not a true pepper, but dried roasted berries derived from Schinus terebinthifolius, a flowering plant in the family Anacardiaceae, native to South America. Common names include Brazilian Pepper, Rose Pepper and Christmasberry. Pink peppercorns are used as a spice to add a mild pepper-like taste to foods. It may potentially cause an irritating skin effect and has been associated with atopic dermatitis in canines. Interestingly, S. terebinthifolius is a member of the family Anacardiaceae, which include plants in the genus Anacardium (cashew nut) and Pistacia (pistachio). No allergens from this plant have been characterized but there is potential for cross-reactivity among different members of the Anacardiaceae family.
This is the first reported case of a patient developing anaphylaxis after pink peppercorn ingestion. Patients with tree nut allergies may need to be educated regarding this potential allergen.
PMCID: PMC3512604
19.  Guidelines for the Diagnosis and Management of Food Allergy in the United States 
Food allergy is an important public health problem that affects children and adults and may be increasing in prevalence. Despite the risk of severe allergic reactions and even death, there is no current treatment for food allergy: the disease can only be managed by allergen avoidance or treatment of symptoms. The diagnosis and management of food allergy also may vary from one clinical practice setting to another. Finally, because patients frequently confuse nonallergic food reactions, such as food intolerance, with food allergies, there is an unfounded belief among the public that food allergy prevalence is higher than it truly is. In response to these concerns, the National Institute of Allergy and Infectious Diseases, working with 34 professional organizations, federal agencies, and patient advocacy groups, led the development of clinical guidelines for the diagnosis and management of food allergy. These Guidelines are intended for use by a wide variety of health care professionals, including family practice physicians, clinical specialists, and nurse practitioners. The Guidelines include a consensus definition for food allergy, discuss comorbid conditions often associated with food allergy, and focus on both IgE-mediated and non-IgE-mediated reactions to food. Topics addressed include the epidemiology, natural history, diagnosis, and management of food allergy, as well as the management of severe symptoms and anaphylaxis. These Guidelines provide 43 concise clinical recommendations and additional guidance on points of current controversy in patient management. They also identify gaps in the current scientific knowledge to be addressed through future research.
PMCID: PMC4241964  PMID: 21134576
food; allergy; anaphylaxis; diagnosis; disease management; guidelines
20.  Food allergy: Diagnosis, management & emerging therapies 
IgE-mediated food allergy is an important health concern with increasing prevalence worldwide. Manifestations of IgE-mediated food allergy include urticaria, angioedema, pruritus, difficulty in breathing, laryngeal oedema, vomiting, diarrhoea and/or hypotension within minutes to two hours of the offending food's ingestion. Diagnosis requires both a careful history and supportive testing with laboratory studies and possibly oral food challenges. Current treatment of food allergy focuses on avoidance of the allergen and prompt emergency management of reactions. Epinephrine autoinjectors are provided to patients for the treatment of severe reactions. More research is needed to determine the optimal timing with which to introduce common allergens into a child's diet to possibly prevent the development of food allergy. Novel therapies are under investigation given the difficulty of allergen avoidance and the potentially fatal nature of reactions. Both allergen specific therapies such as oral, sublingual and epicutaneous immunotherapy and allergen non-specific therapies such the Chinese herbal formula FAHF-2 and omalizumab show promise though more data on efficacy and long-term safety are needed before these therapies become mainstream.
PMCID: PMC4164992  PMID: 25109714
Anaphylaxis; avoidance; diagnosis; food allergy; skin prick test; testing; treatment
21.  430 Comparative Analysis of Patients with Birch Pollinosis and Patients with Associated Plant Food Allergy 
Even 70% patients allergic to pollens of plants are developing undesirable symptoms after eating foods of the plant origin. It is most often a result of the cross-allergy between these allergens. The aim of the study was to compare the group of patients with pollinosis with patients with pollinosis and food allergy.
Fifty eight patients at the age above 16 were included in the study. Patients were divided into 2 groups. Patients included in the first group were birch allergic without any symptoms after eating food (23 persons). Patients in the other group had birch pollen allergy and they had reported clinical symptoms after eating foods such as: apple, celery, carrot, tomato, banana, peach, peanut and hazelnut (35 persons). The skin prick tests with pollen and food allergens (commercial and native) and serum IgE concentration (total and specific) were determined for all individuals. The immunoblotting was performed for the patients with the positive value of birch, apple, celery and/or carrot specific IgE to confirm the cross-reactivity.
Patients with pollinosis and symptoms after eating plant foods were characterized by a significantly larger percentage of positive skin tests with the hazel allergen. In the first group patients revealed positive results of skin tests with food allergens, although they didn't reported the problem after consumption of them. No difference in total IgE levels was found between the 2 groups (271.5 ± 403.8 IU/mL vs 242.5 ± 340.9 IU/mL). Patients with birch allergy and hypersensitivity to food allergens showed significantly higher birch pollen specific IgE levels (11.8 ± 14.1 IU/mL vs 4.1 ± 6.6 IU/mL).
Sixty percent of all the patients with birch pollinosis reported manifestations symptoms after eating certain kind of food. These patients had most often clinical symptoms after eating apples, hazelnuts and of peaches, and less frequently symptoms after eating carrots, celery, peanuts, tomatoes and bananas. Although it seems that false positive results of skin tests with food allergens in the control group and the high level of the birch specific IgE might be the predictive factor of the allergy which may develop later; they require further studies.
PMCID: PMC3513115
22.  Kidney Bean: A Major Sensitizer among Legumes in Asthma and Rhinitis Patients from India 
PLoS ONE  2011;6(11):e27193.
The prevalence of IgE mediated food allergies has increased over the last two decades. Food allergy has been reported to be fatal in highly sensitive individuals. Legumes are important food allergens but their prevalence may vary among different populations. The present study identifies sensitization to common legumes among Indian population, characterizes allergens of kidney bean and establishes its cross reactivity with other legumes.
Patients (n = 355) with history of legume allergy were skin prick tested (SPT) with 10 legumes. Specific IgE (sIgE) and total IgE were estimated in sera by enzyme-linked immunosorbent assay. Characterization of kidney bean allergens and their cross reactivity was investigated by immunobiochemical methods. Identification of major allergens of kidney bean was carried out by mass spectrometry.
Principal Findings
Kidney bean exhibited sensitization in 78 (22.0%) patients followed by chickpea 65 (18.0%) and peanut 53 (15%). SPT positive patients depicted significantly elevated sIgE levels against different legumes (r = 0.85, p<0.0001). Sera from 30 kidney bean sensitive individuals exhibited basophil histamine release (16–54%) which significantly correlated with their SPT (r = 0.83, p<0.0001) and sIgE (r = 0.99, p<0.0001). Kidney bean showed eight major allergens of 58, 50, 45, 42, 40, 37, 34 and 18 kDa on immunoblot and required 67.3±2.51 ng of homologous protein for 50% IgE inhibition. Inhibition assays revealed extensive cross reactivity among kidney bean, peanut, black gram and pigeon pea. nLC-MS/MS analysis identified four allergens of kidney bean showing significant matches with known proteins namely lectin (phytohemagglutinin), phaseolin, alpha-amylase inhibitor precursor and group 3 late embryogenesis abundant protein.
Among legumes, kidney bean followed by chick pea and peanut are the major allergic triggers in asthma and rhinitis patients in India. Kidney bean showed eight major allergens and cross reacted with other legumes. A combination of SPT, sIgE and histamine release assay is helpful in allergy diagnosis.
PMCID: PMC3212544  PMID: 22096535
23.  Tick-induced allergies: mammalian meat allergy, tick anaphylaxis and their significance 
Asia Pacific Allergy  2015;5(1):3-16.
Serious tick-induced allergies comprise mammalian meat allergy following tick bites and tick anaphylaxis. Mammalian meat allergy is an emergent allergy, increasingly prevalent in tick-endemic areas of Australia and the United States, occurring worldwide where ticks are endemic. Sensitisation to galactose-α-1,3-galactose (α-Gal) has been shown to be the mechanism of allergic reaction in mammalian meat allergy following tick bite. Whilst other carbohydrate allergens have been identified, this allergen is unique amongst carbohydrate food allergens in provoking anaphylaxis. Treatment of mammalian meat anaphylaxis involves avoidance of mammalian meat and mammalian derived products in those who also react to gelatine and mammalian milks. Before initiating treatment with certain therapeutic agents (e.g., cetuximab, gelatine-containing substances), a careful assessment of the risk of anaphylaxis, including serological analysis for α-Gal specific-IgE, should be undertaken in any individual who works, lives, volunteers or recreates in a tick endemic area. Prevention of tick bites may ameliorate mammalian meat allergy. Tick anaphylaxis is rare in countries other than Australia. Tick anaphylaxis is secondarily preventable by prevention and appropriate management of tick bites. Analysis of tick removal techniques in tick anaphylaxis sufferers offers insights into primary prevention of both tick and mammalian meat anaphylaxis. Recognition of the association between mammalian meat allergy and tick bites has established a novel cause and effect relationship between an environmental exposure and subsequent development of a food allergy, directing us towards examining environmental exposures as provoking factors pivotal to the development of other food allergies and refocusing our attention upon causation of allergy in general.
PMCID: PMC4313755  PMID: 25653915
Mammalian meat; Ticks; Anaphylaxis; Alpha-gal; Cetuximab
24.  Purification, biochemical, and immunological characterisation of a major food allergen: different immunoglobulin E recognition of the apo- and calcium-bound forms of carp parvalbumin 
Gut  2000;46(5):661-669.
BACKGROUND—Almost 4% of the population suffer from food allergy which is an adverse reaction to food with an underlying immunological mechanism.
AIMS—To characterise one of the most frequent IgE defined food allergens, fish parvalbumin.
METHODS—Tissue and subcellular distribution of carp parvalbumin was analysed by immunogold electron microscopy and cell fractionation. Parvalbumin was purified to homogeneity, analysed by mass spectrometry and circular dichroism (CD) spectroscopy, and its allergenic activity was analysed by IgE binding and basophil histamine release tests.
RESULTS—The isoelectric point (pI) 4.7 form of carp parvalbumin, a three EF-hand calcium-binding protein, was purified to homogeneity. CD analysis revealed a remarkable stability and refolding capacity of calcium-bound parvalbumin. This may explain why parvalbumin, despite cooking and exposure to the gastrointestinal tract, can sensitise patients. Purified parvalbumin reacted with IgE of more than 95% of individuals allergic to fish, induced dose-dependent basophil histamine release and contained, on average, 83% of the IgE epitopes present in other fish species. Calcium depletion reduced the IgE binding capacity of parvalbumin which, according to CD analysis, may be due to conformation-dependent IgE recognition.
CONCLUSIONS—Purified carp parvalbumin represents an important cross reactive food allergen. It can be used for in vitro and in vivo diagnosis of fish-induced food allergy. Our finding that the apo-form of parvalbumin had a greatly reduced IgE binding capacity indicates that this form may be a candidate for safe immunotherapy of fish-related food allergy.

Keywords: food allergy; parvalbumin; circular dichroism; epitopes; antibodies; immunochemistry
PMCID: PMC1727915  PMID: 10764710
25.  Allergenic potential and enzymatic resistance of buckwheat 
Buckwheat is known as a health food but is one of the major food allergens triggering potentially fatal anaphylaxis in Asia, especially in Japan and Korea. This study was conducted to investigate the characteristic of enzymatic resistance of buckwheat protein and allergenic potential. Enzymatic resistance of buckwheat protein was performed with in vitro digestibility test in simulated gastric fluid (SGF), pH 1.2, using pepsin and simulated intestinal fluid (SIF) using chymotrypsin. Reactivity of buckwheat proteins to human IgE was performed using six allergic patients sensitized to buckwheat. Buckwheat's IgE levels were measured using the Phadia UniCAP-system. Buckwheat protein, 16 kDa, still remained after 30 min treatment of pepsin on SDS-PAGE. Even though 16 kDa almost disappeared after 60 min treatment, two out of the six buckwheat patients' sera showed reactivity to hydrolysate after 60 min treatment, indicating that allergenicity still remained. In simulated intestinal fluid (SIF) using chymotrypsin, buckwheat protein, 24 kDa, showed resistance to hydrolysis with chymotrypsin on SDS-PAGE, and still had allergenicity based on the result of ELISA. Our results suggest that buckwheat proteins have strong resistance to enzyme degradation. This may be attributed in part to the allergenic potential of buckwheat. Further study should be continued regarding buckwheat allergy.
PMCID: PMC3572223  PMID: 23423876
Buckwheat; hydrolysis; pepsin; chymotrypsin; allergenicity

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