Identifying and managing patients at risk of severe allergic reactions to food: Report from two iFAAM workshops

Food allergy affects a small but important number of children and adults. Much of the morbidity associated with food allergy is driven by the fear of a severe reaction and fatalities continue to occur. Foods are the commonest cause of anaphylaxis. One of the aims of the European Union‐funded Integrated Approaches to Food Allergen and Allergy Risk Management (iFAAM) project was to improve the identification and management of children and adults at risk of experiencing a severe reaction. A number of interconnected studies within the project have focused on quantifying the severity of allergic reactions; the impact of food matrix, immunological factors on severity of reactions; the impact of co‐factors such as medications on the severity of reactions; utilizing single‐dose challenges to understand threshold and severity of reactions; and community studies to understand the experience of patients suffering real‐life allergic reactions to food. Associated studies have examined population thresholds and co‐factors such as exercise and stress. This paper summarizes two workshops focused on the severity of allergic reactions to food. It outlines the related studies being undertaken in the project indicating how they are likely to impact on our ability to identify individuals at risk of severe reactions and improve their management.     

Food allergy—From food avoidance to active treatment

The prevalence of food allergy (FA) has increased too rapidly, possibly due to environmental factors. The guidelines recommend strict allergen avoidance, but FA is still the main cause of anaphylaxis in all age groups. Immunotherapy is the only treatment able to change the course of allergic disease, and oral immunotherapy (OIT) is the more effective route in FA. However, it carries the risk of adverse reactions, including anaphylaxis. To improve OIT safety, adjuvant therapy with the immunoglobulin E (IgE) monoclonal antibody omalizumab has been extensively used. Results suggest particular benefit in patients with high risk of fatal anaphylaxis. An alternative approach is to use omalizumab instead of OIT to prevent severe allergic reactions upon accidental exposure. This paper reviews current evidence regarding IgE-mediated FA, focusing on natural tolerance and food sensitization acquisition, and on avoidance measures and their limitations.     

The management of anaphylaxis in childhood: position paper of the European academy of allergology and clinical immunology

Anaphylaxis is a growing paediatric clinical emergency that is difficult to diagnose because a consensus definition was lacking until recently. Many European countries have no specific guidelines for anaphylaxis. This position paper prepared by the EAACI Taskforce on Anaphylaxis in Children aims to provide practical guidelines for managing anaphylaxis in childhood based on the limited evidence available. Intramuscular adrenaline is the acknowledged first-line therapy for anaphylaxis, in hospital and in the community, and should be given as soon as the condition is recognized. Additional therapies such as volume support, nebulized bronchodilators, antihistamines or corticosteroids are supplementary to adrenaline. There are no absolute contraindications to administering adrenaline in children. Allergy assessment is mandatory in all children with a history of anaphylaxis because it is essential to identify and avoid the allergen to prevent its recurrence. A tailored anaphylaxis management plan is needed, based on an individual risk assessment, which is influenced by the child's previous allergic reactions, other medical conditions and social circumstances. Collaborative partnerships should be established, involving school staff, healthcare professionals and patients' organizations. Absolute indications for prescribing self-injectable adrenaline are prior cardiorespiratory reactions, exercise-induced anaphylaxis, idiopathic anaphylaxis and persistent asthma with food allergy. Relative indications include peanut or tree nut allergy, reactions to small quantities of a given food, food allergy in teenagers and living far away from a medical facility. The creation of national and European databases is expected to generate better-quality data and help develop a stepwise approach for a better management of paediatric anaphylaxis.     

Restaurant staff's knowledge of anaphylaxis and dietary care of people with allergies

Background Deaths caused by food‐induced anaphylactic reactions are increasing, with most caused by food purchased outside the home. Primary prevention by allergen avoidance is desirable, but is easier in the home than when eating out, where the responsibility is shared with restaurant staff. Objective To investigate restaurant staff's knowledge about food allergies. Method A structured telephone questionnaire was administered to a member of staff at 90 table‐service restaurants in Brighton. Results Fifty‐six percent (90/162) restaurants that were contacted agreed to participate. Responders included seven owners, 48 managers, 20 waiters and 15 chefs. Ninety per cent (81/90) reported food hygiene training; 33% (30/90) reported specific food allergy training. Fifty‐six percent (50/90) could name three or more food allergens. Eighty‐one percent reported confidence (very or somewhat) in providing a safe meal to a food‐allergic customer. Answers to true–false questions indicated some frequent misunderstandings: 38% believed an individual experiencing a reaction should drink water to dilute the allergen; 23% thought consuming a small amount of an allergen is safe; 21% reported allergen removal from a finished meal would render it safe; 16% agreed cooking food prevents it causing allergy and 12% were unaware allergy could cause death. Forty‐eight percent expressed interest in further training on food allergy. Conclusions and Clinical Relevance Despite a high confidence level, there are obvious gaps in restaurant staff's knowledge of allergy. Food‐allergic patients need to be aware of this and adapt their behaviour accordingly. Our data challenge the impact of current food allergy training practice for restaurant staff, and support the need for more rigorous and accessible training. Cite this as: S. Bailey, R. Albardiaz, A. J. Frew and H. Smith, Clinical & Experimental Allergy, 2011 (41) 713–717.     

Treatments for food allergy: how close are we?

Food allergy continues to be a challenging health problem, with prevalence continuing to increase and anaphylaxis still an unpredictable possibility. While improvements in diagnosis are more accurately identifying affected individuals, treatment options remain limited. The cornerstone of treatment relies on strict avoidance of the offending allergens and education regarding management of allergic reactions. Despite vigilance in avoidance, accidental ingestions and reactions continue to occur. With recent advances in the understanding of humoral and cellular immune responses in food allergy and mechanisms of tolerance, several therapeutic strategies for food allergies are currently being investigated with the hopes of providing a cure or long-term remission from food allergy.     

School readiness for children with food allergies.

BACKGROUND: Food allergy reactions and anaphylaxis may occur in children while at school. However, information regarding school readiness for children with food allergies is unknown. OBJECTIVE: To identify school education and prevention and treatment policies for food-allergic children in Michigan. METHODS: A questionnaire assessing food allergy awareness and avoidance and treatment strategies was mailed to a randomized sample (n = 273) of 2,082 public elementary school principals. RESULTS: One hundred four responses representing 109 schools were collected. From school estimates of 66,598 children, there was a 1.7% self-reported prevalence of food allergy. The most common allergens were milk and peanut, followed by tree nuts, shellfish, egg, and wheat. Affected children were identified primarily through office records, with few reporting individual emergency plans or designated classrooms, teachers, or lunch tables. Methods of food allergy education included parents of students and in-services. Avoidance strategies, food substitution, and "no-sharing" policies were common, whereas other measures such as food-label-teaching were uncommon. A minority of schools had epinephrine immediately accessible, either in the student's classroom, carried by the student, or passed by teachers. Principals, nurses, and teachers were most often trained to administer epinephrine. CONCLUSIONS: There appears to be a need for schools to formally educate staff on food allergy, provide information on prevention measures such as reading of food labels, establish immediate accessibility to emergency epinephrine, and train staff for appropriate epinephrine use.     

Reaction phenotypes in IgE-mediated food allergy and anaphylaxis

ObjectiveFood allergy encompasses a range of food hypersensitivities. Different clinical phenotypes for food allergy likely exist in much the same way as endotype discovery is now a major research theme in asthma. We discuss the emerging evidence for different reaction phenotypes (ie, symptoms experienced after allergen exposure in food allergic individuals) and their relevance for clinical practice.Data SourcesPublished and unpublished literature relating to reaction phenotypes in food allergy.Study SelectionsAuthors assessment of the available data.ResultsFood anaphylaxis may be pathophysiologically different than anaphylaxis caused by nonfood triggers. Currently, there are no robust, clinically useful predictors of severity in food allergy. It is likely that patient-specific reaction phenotypes exist in food allergy, which may affect the risk of severe anaphylaxis. Allergen immunotherapy may modulate these phenotypes.ConclusionData are emerging to confirm our clinical experience that many food allergic patients experience stereotypical symptoms after allergen exposure, both in the community and at supervised oral food challenge, in a manner that varies among patients. Integrating data sets from different cohorts and applying unbiased machine-based learning analyses may demonstrate specific food allergy endotypes in a similar way to asthma. Whether this results in improvements in patient management (eg, through facilitating risk stratification or affecting the decision to prescribe an epinephrine autoinjector and, perhaps, the number of devices) remains to be determined, but given our current inability to predict which patients are most at risk of severe food allergic reactions, this will clearly be an important area of research in the future.     

EAACI Food Allergy and Anaphylaxis Guidelines: diagnosis and management of food allergy

Food allergy can result in considerable morbidity, impact negatively on quality of life, and prove costly in terms of medical care. These guidelines have been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Guidelines for Food Allergy and Anaphylaxis Group, building on previous EAACI position papers on adverse reaction to foods and three recent systematic reviews on the epidemiology, diagnosis, and management of food allergy, and provide evidence‐based recommendations for the diagnosis and management of food allergy. While the primary audience is allergists, this document is relevant for all other healthcare professionals, including primary care physicians, and pediatric and adult specialists, dieticians, pharmacists and paramedics. Our current understanding of the manifestations of food allergy, the role of diagnostic tests, and the effective management of patients of all ages with food allergy is presented. The acute management of non‐life‐threatening reactions is covered in these guidelines, but for guidance on the emergency management of anaphylaxis, readers are referred to the related EAACI Anaphylaxis Guidelines.     

The impact of oral food challenge tests on food allergy health‐related quality of life

Food allergy health‐related quality of life (FAQOL) has been shown to improve after food challenge, but it is unknown whether this improvement is attributed to the procedure itself. Using the Food Allergy Quality of Life Questionnaire–Parent Form, we assessed FAQOL changes over time for children who underwent food challenges in the only paediatric allergy clinic in Ireland. Of 54 children who had a food challenge between September 2012 and February 2013, 25 were positive (allergic) and 29 were negative (nonallergic). FAQOL improved significantly from 2 months prechallenge to 2 months postchallenge for both groups, but began to decrease at 6 months postchallenge in allergic patients. Our findings confirm the positive therapeutic effect of the food challenge on FAQOL; however, the effect appears to wane between 2 and 6 months postchallenge in those confirmed food‐allergic, highlighting the importance of regular contact with families of food‐allergic children after the food challenge.     

ICON: food allergy

Food allergies can result in life-threatening reactions and diminish quality of life. In the last several decades, the prevalence of food allergies has increased in several regions throughout the world. Although more than 170 foods have been identified as being potentially allergenic, a minority of these foods cause the majority of reactions, and common food allergens vary between geographic regions. Treatment of food allergy involves strict avoidance of the trigger food. Medications manage symptoms of disease, but currently, there is no cure for food allergy. In light of the increasing burden of allergic diseases, the American Academy of Allergy, Asthma & Immunology; European Academy of Allergy and Clinical Immunology; World Allergy Organization; and American College of Allergy, Asthma & Immunology have come together to increase the communication of information about allergies and asthma at a global level. Within the framework of this collaboration, termed the International Collaboration in Asthma, Allergy and Immunology, a series of consensus documents called International Consensus ON (ICON) are being developed to serve as an important resource and support physicians in managing different allergic diseases. An author group was formed to describe the natural history, prevalence, diagnosis, and treatment of food allergies in the context of the global community.     

EAACI Guidelines on allergen immunotherapy: IgE‐mediated food allergy

Food allergy can result in considerable morbidity, impairment of quality of life, and healthcare expenditure. There is therefore interest in novel strategies for its treatment, particularly food allergen immunotherapy (FA‐AIT) through the oral (OIT), sublingual (SLIT), or epicutaneous (EPIT) routes. This Guideline, prepared by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force on Allergen Immunotherapy for IgE‐mediated Food Allergy, aims to provide evidence‐based recommendations for active treatment of IgE‐mediated food allergy with FA‐AIT. Immunotherapy relies on the delivery of gradually increasing doses of specific allergen to increase the threshold of reaction while on therapy (also known as desensitization) and ultimately to achieve post‐discontinuation effectiveness (also known as tolerance or sustained unresponsiveness). Oral FA‐AIT has most frequently been assessed: here, the allergen is either immediately swallowed (OIT) or held under the tongue for a period of time (SLIT). Overall, trials have found substantial benefit for patients undergoing either OIT or SLIT with respect to efficacy during treatment, particularly for cow's milk, hen's egg, and peanut allergies. A benefit post‐discontinuation is also suggested, but not confirmed. Adverse events during FA‐AIT have been frequently reported, but few subjects discontinue FA‐AIT as a result of these. Taking into account the current evidence, FA‐AIT should only be performed in research centers or in clinical centers with an extensive experience in FA‐AIT. Patients and their families should be provided with information about the use of FA‐AIT for IgE‐mediated food allergy to allow them to make an informed decision about the therapy.     

EAACI Food Allergy and Anaphylaxis Guidelines. Primary prevention of food allergy

Food allergy can have significant effects on morbidity and quality of life and can be costly in terms of medical visits and treatments. There is therefore considerable interest in generating efficient approaches that may reduce the risk of developing food allergy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on Prevention and is part of the EAACI Guidelines for Food Allergy and Anaphylaxis. It aims to provide evidence‐based recommendations for primary prevention of food allergy. A wide range of antenatal, perinatal, neonatal, and childhood strategies were identified and their effectiveness assessed and synthesized in a systematic review. Based on this evidence, families can be provided with evidence‐based advice about preventing food allergy, particularly for infants at high risk for development of allergic disease. The advice for all mothers includes a normal diet without restrictions during pregnancy and lactation. For all infants, exclusive breastfeeding is recommended for at least first 4–6 months of life. If breastfeeding is insufficient or not possible, infants at high‐risk can be recommended a hypoallergenic formula with a documented preventive effect for the first 4 months. There is no need to avoid introducing complementary foods beyond 4 months, and currently, the evidence does not justify recommendations about either withholding or encouraging exposure to potentially allergenic foods after 4 months once weaning has commenced, irrespective of atopic heredity. There is no evidence to support the use of prebiotics or probiotics for food allergy prevention.     

Pathogenesis of IgE‐mediated food allergy

Food allergy is a prevalent disease for which there is no current treatment beyond careful food avoidance. Accidental exposure to foods causes reactions in allergic individuals that can range in severity from mild skin reactions to severe and life‐threatening anaphylaxis, and there are no validated tools to predict severity of reactions. A greater understanding of the pathogenesis of food allergy is needed to develop prevention and treatment strategies for food allergy. In the last few years, there have been significant developments in the field of food allergy that have led to new ideas about food allergy prevention, diagnosis, and treatment. This review will discuss these recent advances in the food allergy field as well as identify gaps in our knowledge about the immune mechanisms of allergy and tolerance to foods.     

Development of a questionnaire to measure quality of life in families with a child with food allergy

BACKGROUND: Food allergy is potentially severe, affects approximately 5% of children, and requires numerous measures for food avoidance to maintain health. The effect of this disease on health-related quality of life (HRQL) has been documented by using generic instruments, but no disease-specific instrument is available. OBJECTIVE: To create a validated, food allergy-specific HRQL instrument to measure parental burden associated with having a child with food allergy: the Food Allergy Quality of Life-Parental Burden questionnaire. METHODS: After identification of 74 items affecting families with children with food allergy, 88 families were approached for effect scoring. Final items were generated by score results, elimination of redundancies, and content review. Resulting high-effect areas were queried for validation with a 7-point Likert scale. A final instrument including 17 items and 2 expectation of outcome questions was distributed to 352 families for validation. RESULTS: Areas of effect included family/social activities (restaurant meals, social activities, child care, vacation), school, time for meal preparation, health concerns, and emotional issues. Validation steps showed strong internal validity (Cronbach alpha, 0.95) and good correlation with expectation of outcome questions ( r = 0.412; P < .01) and scores on a generic HRQL instrument, the Children's Health Questionnaire-PF50 ( r = -0.36 to -0.4; P < .01). The instrument showed the ability to discriminate by disease burden: parents whose children had multiple (>2) food allergies were more affected than parents whose children had fewer allergies (scores, 3.1 vs 2.6; P < .001). CONCLUSIONS: The Food Allergy Quality of Life-Parental Burden demonstrates strong internal and cross-sectional validity. Its discriminative ability suggests that it will be a useful tool to measure outcomes in treatment studies of food allergy for children.     

Beyond allergen avoidance: update on developing therapies for peanut allergy

PURPOSE OF REVIEW: Food allergy has emerged as a significant health problem. Peanut allergy is a major cause of food-induced fatal and near fatal anaphylactic reactions, and the incidence in children is increasing. Attempts to manage peanut allergy by strict avoidance are often unsuccessful. The purpose of this review is to highlight the most promising novel approaches for treating peanut allergy beyond allergen avoidance. RECENT FINDINGS: In the past 5 years much effort has been devoted to developing a treatment for peanut allergy. A recent clinical trial showed that monthly injections of humanized recombinant anti-IgE antibodies increased the threshold for allergic responses of peanut-sensitive individuals, at least to small amounts of peanut protein. However, this treatment cannot cure peanut allergy, and continuous monthly injections are necessary to maintain protection. Developing new therapies for the treatment of peanut allergy is essential. In reviewing publications between 2003 and 2005, several novel therapeutic approaches, tested in the murine model of peanut anaphylaxis appeared promising. Immunotherapy with engineered recombinant peanut protein and bacterial adjuvant significantly protected peanut allergic mice from anaphylaxis. It was also found that a Chinese herbal medicine formula called Food Allergy Herbal Formula-2 completely blocked anaphylaxis up to 5 weeks following therapy. These potent therapeutic effects are associated with immunoregulation of Th1 and Th2 responses. SUMMARY: Although there is no effective and safe therapy for food allergy, many novel approaches are under investigation. Some of these approaches may provide allergists with effective treatments in the near future.     

Development and validation of the Food Allergy Quality of Life Questionnaire – Adult Form

Background: Health‐related quality of life (HRQL) may be affected by food allergy. Presently, no disease‐specific HRQL questionnaire exists for food allergic adults. Therefore, we developed and validated the Food Allergy Quality of Life Questionnaire – Adult Form (FAQLQ‐AF) in the Dutch language. Methods: Twenty‐two food allergic patients (≥18 years) were interviewed and generated 180 HRQL items. The most important items were identified by 54 food allergic patients using the clinical impact method resulting in the FAQLQ‐AF containing 29 items (score range 1 ‘not troubled’ to 7 ‘extremely troubled’). The FAQLQ‐AF, the Food Allergy Independent Measure (FAIM) and a generic HRQL questionnaire (RAND‐36) were sent to 100 other food allergic adults for cross‐sectional validation of the FAQLQ‐AF. Results: Cross‐sectional validity was assessed by the correlation between FAQLQ‐AF and FAIM (ρ = 0.76, P < 0.001). The FAQLQ‐AF had excellent internal consistency (Cronbach’s α = 0.97). The FAQLQ‐AF discriminated between patients who differ in severity of symptoms (anaphylaxis vs no anaphylaxis, total FAQLQ‐AF score 4.9 vs 4.1; P = 0.041) and number of food allergies (>3 food allergies vs≤3 food allergies, total FAQLQ‐AF score 5.2 vs 4.2; P = 0.008). The total FAQLQ‐AF score was correlated with one RAND‐36 scale (convergent/discriminant validity). Conclusions: The FAQLQ‐AF is the first disease‐specific HRQL questionnaire for food allergic adults and reflects the most important issues that food allergic patients have to face. The questionnaire is valid, reliable and discriminates between patients with different disease characteristics. The FAQLQ‐AF is short and easy to use and may therefore be a useful tool in clinical research.     

Introducing chemists to food allergy

Adverse reactions to food may be toxic or non toxic, depending on the susceptibility to a certain food; non toxic reactions that involve immune mechanisms are termed allergy if they are IgE-mediated. If no immunological mechanism is responsible, it is termed intolerance . The following disorders are considered a consequence of food allergy: gastrointestinal reactions (oral allergy syndrome, vomiting, diarrhea, protein-induced enterocolitic syndrome, eosinophilic gastroenteritis); respiratory reactions (rhinitis, asthma, laryngeal edema); cutaneous reactions (urticaria-angioedema, atopic dermatitis); anaphylaxis. There is much recent evidence to consider celiac disease an immunological disorder. Food allergy diagnosis is based on history, SPT, specific IgE, food challenges. DBPCFC is fundamental for diagnosing true food allergy; patients who have had anaphylaxis to food must not undergo DBPCFC. Rapidly progressive respiratory reactions and anaphylactic shock are life-threatening reactions that can be caused by food allergy. The doses of food inducing anaphylaxis can be very low, therefore commercial cross-contamination with an unsuspected food during food processing can be risky for the food allergic patient. The prevention of severe anaphylactic food reactions may lie in interdisciplinary collaboration among allergologists, chemists, food technologists, and experts in food industry research.     

Can we identify patients at risk of life‐threatening allergic reactions to food?

Anaphylaxis has been defined as a ‘severe, life‐threatening generalized or systemic hypersensitivity reaction’. However, data indicate that the vast majority of food‐triggered anaphylactic reactions are not life‐threatening. Nonetheless, severe life‐threatening reactions do occur and are unpredictable. We discuss the concepts surrounding perceptions of severe, life‐threatening allergic reactions to food by different stakeholders, with particular reference to the inclusion of clinical severity as a factor in allergy and allergen risk management. We review the evidence regarding factors that might be used to identify those at most risk of severe allergic reactions to food, and the consequences of misinformation in this regard. For example, a significant proportion of food‐allergic children also have asthma, yet almost none will experience a fatal food‐allergic reaction; asthma is not, in itself, a strong predictor for fatal anaphylaxis. The relationship between dose of allergen exposure and symptom severity is unclear. While dose appears to be a risk factor in at least a subgroup of patients, studies report that individuals with prior anaphylaxis do not have a lower eliciting dose than those reporting previous mild reactions. It is therefore important to consider severity and sensitivity as separate factors, as a highly sensitive individual will not necessarily experience severe symptoms during an allergic reaction. We identify the knowledge gaps that need to be addressed to improve our ability to better identify those most at risk of severe food‐induced allergic reactions.     

The impact of food allergy on the daily activities of children and their families.

BACKGROUND: Food allergy affects a significant number of children, and its management requires considerable time and vigilance. OBJECTIVE: To determine the impact of food allergy on the daily activities of food allergic children and their families. METHODS: Caregivers of food allergic children from a university-based allergy practice completed a questionnaire that evaluated their perception of the impact of their child's food allergy on family activities. RESULTS: Of the 87 families who completed the study, more than 60% of caregivers reported that food allergy significantly affected meal preparation and 49% or more indicated that food allergy affected family social activities. Forty-one percent of parents reported a significant impact on their stress levels and 34% reported that food allergy had an impact on school attendance, with 10% choosing to home school their children because of food allergy. The number of food allergies had a significant impact on activity scores, but the existence of comorbid conditions such as asthma and atopic dermatitis did not significantly affect the results. CONCLUSIONS: Food allergy has a significant effect on activities of families of food allergic children. Further study is needed to determine more detailed effects of food allergy on parent-child interactions and development.     

Food reactions during avoidance: Focus on peanut

ObjectivePeanut allergy has historically been difficult to manage, with most cases persisting into adulthood. Novel therapies for peanut allergy treatment are on the horizon, yet allergists must maintain a robust understanding of the risks and benefits of the current standard of therapy, avoidance diet.Data SourcesA comprehensive literature search using PubMed of reviews and clinical articles was performed.Study SelectionsArticles discussing peanut or other food-related allergic reactions, accidental exposures or anaphylaxis pertinent to avoidance diet or comparative to oral immunotherapy trials were selected.ResultsPeanut remains a leading allergen associated with accidental ingestions responsible for food-related reactions, both mild and severe. Fatal reactions, however, are rare and measures such as anaphylaxis plans can significantly decrease the risk of accidental anaphylaxis. Patients may over estimate situations thought to increase risk for reactions to peanut, such as inhalation or contact through skin. In oral immunotherapy trials, the rate of anaphylaxis secondary to treatment was significantly higher than avoidance practices.ConclusionClinicians should continue to discuss avoidance as a viable option for long-term peanut allergy management and empower patients to differentiate relevant situations in which accidental reactions might occur.