Recent advances in understanding and preventing peanut and tree nut hypersensitivity.

Peanut allergy, the most persistent and deadly of the food allergies, has become more prevalent worldwide in recent decades. Numerous explanations have been offered for the rise in peanut allergy, which has been more pronounced in Western, industrialized nations. In infants who are at increased risk of peanut allergy, new evidence indicates that early introduction of peanuts can help prevent allergy development. This counterintuitive finding directly contradicts the previously established practice of peanut avoidance for high-risk infants but is supported by clinical and basic science evidence. Here, we review the literature contributing to our evolving understanding of nut allergy, emphasizing the translation of this work to clinical practice

The Influence of Dietary Factors on Child Food Allergies

Solid food introduction guidelines were recently amended to suggest that earlier introduction of peanuts is associated with a decreased prevalence of peanut allergies in high-risk children. This study aimed to determine whether there is a relationship between timing of introduction to the eight most common food allergens and the development of a food allergy. A total of 177 biological mothers of school-aged New Hampshire children completed the survey, but some were excluded due to answering \u3c50% of the survey or not consenting to participate in the study. This left data on 101 participants, and the number of participants then varied between the various food allergens. Out of the 22 children with a milk allergy, 10 children were introduced to milk when they were less than 12 months old and 12 children were introduced at or after one year old. Fifty-nine percent of those introduced before 12 months of age developed a milk allergy, while only 17% of those introduced at or past 12 months developed a milk allergy (p = 0.00). Out of the 55 participants that developed a peanut/tree nut allergy, 12 were introduced to peanuts/tree nuts before the age of 12 months, and 43 introduced after. This means that 63% of those introduced before a year developed an allergy, while only 33% introduced later developed an allergy (p = 0.01). Although not significant, the results for egg, wheat, and peanut also demonstrated that earlier introduction may be associated with an increased risk of an allergy to that food. When only one child per family was considered, to exclude genetic confounders, the only significant value was for a milk allergy, in which 64% of children introduced before 12 months developed a food allergy, while only 18% of children introduced at or after 12 months developed one (p = 0.00). Results were similar even after the exclusion of child one and two. The results of this study concur with the recommendation of introducing milk after one year, but do not support earlier introduction to other food allergens in the general population

An algorithm for diagnosing IgE-mediated food allergy in study participants who do not undergo food challenge.

BACKGROUND: Food allergy diagnosis in clinical studies can be challenging. Oral food challenges (OFC) are time-consuming, carry some risk and may, therefore, not be acceptable to all study participants. OBJECTIVE: To design and evaluate an algorithm for detecting IgE-mediated food allergy in clinical study participants who do not undergo OFC. METHODS: An algorithm for trial participants in the Barrier Enhancement for Eczema Prevention (BEEP) study who were unwilling or unable to attend OFC was developed. BEEP is a pragmatic, multi-centre, randomized-controlled trial of daily emollient for the first year of life for primary prevention of eczema and food allergy in high-risk infants (ISRCTN21528841). We built on the European iFAAM consensus guidance to develop a novel food allergy diagnosis algorithm using available information on previous allergenic food ingestion, food reaction(s) and sensitization status. This was implemented by a panel of food allergy experts blind to treatment allocation and OFC outcome. We then evaluated the algorithm's performance in both BEEP and Enquiring About Tolerance (EAT) study participants who did undergo OFC. RESULTS: In 31/69 (45%) BEEP and 44/55 (80%) EAT study control group participants who had an OFC the panel felt confident enough to categorize children as "probable food allergy" or "probable no food allergy". Algorithm-derived panel decisions showed high sensitivity 94% (95%CI 68, 100) BEEP; 90% (95%CI 72, 97) EAT and moderate specificity 67% (95%CI 39, 87) BEEP; 67% (95%CI 39, 87) EAT. Sensitivity and specificity were similar when all BEEP and EAT participants with OFC outcome were included. CONCLUSION: We describe a new algorithm with high sensitivity for IgE-mediated food allergy in clinical study participants who do not undergo OFC. CLINICAL RELEVANCE: This may be a useful tool for excluding food allergy in future clinical studies where OFC is not conducted

Profile of allergy-related articles in the primary academic publication for UK General Practitioners

Background: Concern is often expressed about primary health care professionals’ lack of knowledge about allergies, particularly diagnostic testing and the management of atopic disorders. Limited training opportunities in allergy have been documented in both undergraduate and postgraduate education. The British Journal of General Practice is the leading UK-based Family Practice journal, it has a strong clinical focus. The BJGP was established in 1953. It is a high quality journal and is the world’s 2nd most highly cited journal of general practice and primary care. Methods: Keyword search of bjgp.org. Terms used were ‘allergy’, ‘allergies’, ‘allergic’, ‘rhinitis’, ‘urticaria’, ‘eczema’, ‘angioedema’. All titles and articles from 1953 to 2013 were searched. Full copies of relevant publications were downloaded and variables extracted, including title, year of publication, type of article, clinical focus. As a comparator a similar search was conducted for articles about asthma using the search term ‘asthma’. Results: 41 allergy-related articles were identified in the 60 years since the journal was launched. In the same time period there were 147 articles about asthma. In 31 of the 60 years reviewed there were no articles at all about any allergy-related topic. The focus of the articles published were eczema (6), food allergy (6), rhinoconjunctivitis (5), anaphylaxis (4), urticaria (1). There were no articles on angioedema. Some articles addressed multiple atopic disorders, eg ‘Allergic diseases in the elderly’ (1968), ‘Allergic disorders amongst horticultural, agricultural and forestry workers’ [letter] (1965). Conclusions: Allergy has a low profile in the British Journal of General Practice. This low profile persists despite the increasing prevalence of atopic disorders and major national reports highlighting the need for better care of the allergic patient in primary care. Our exploratory study highlights a missed opportunity to educate and inform General Practitioners about allergy through this widely circulated journal. Further work is needed to understand better why so few articles on allergy are published in the BJGP. If the paucity of publications reflects the number of articles submitted then BSACI members interested in informing and improving allergy management in General Practice should include the BJGP on their list of target journals. Where next: To share these observations with the Editor of the BJGP to understand whether they reflect editorial policy or lack of submissions from clinicians and researchers with expertise in allergy. To work with the BJGP to identify collaborative initiatives to address the serious mismatch between the prevalence of allergy in the clinical consultation and the number of allergy- related articles in the literature for GPs

Peanut allergy:effect of environmental peanut exposure in children with filaggrin loss-of-function mutations

BackgroundFilaggrin (FLG) loss-of-function mutations lead to an impaired skin barrier associated with peanut allergy. Household peanut consumption is associated with peanut allergy, and peanut allergen in household dust correlates with household peanut consumption.ObjectiveWe sought to determine whether environmental peanut exposure increases the odds of peanut allergy and whether FLG mutations modulate these odds.MethodsExposure to peanut antigen in dust within the first year of life was measured in a population-based birth cohort. Peanut sensitization and peanut allergy (defined by using oral food challenges or component-resolved diagnostics [CRD]) were assessed at 8 and 11 years. Genotyping was performed for 6 FLG mutations.ResultsAfter adjustment for infantile atopic dermatitis and preceding egg skin prick test (SPT) sensitization, we found a strong and significant interaction between natural log (ln [loge]) peanut dust levels and FLG mutations on peanut sensitization and peanut allergy. Among children with FLG mutations, for each ln unit increase in the house dust peanut protein level, there was a more than 6-fold increased odds of peanut SPT sensitization, CRD sensitization, or both in children at ages 8 years, 11 years, or both and a greater than 3-fold increased odds of peanut allergy compared with odds seen in children with wild-type FLG. There was no significant effect of exposure in children without FLG mutations. In children carrying an FLG mutation, the threshold level for peanut SPT sensitization was 0.92 μg of peanut protein per gram (95% CI, 0.70-1.22 μg/g), that for CRD sensitization was 1.03 μg/g (95% CI, 0.90-1.82 μg/g), and that for peanut allergy was 1.17 μg/g (95% CI, 0.01-163.83 μg/g).ConclusionEarly-life environmental peanut exposure is associated with an increased risk of peanut sensitization and allergy in children who carry an FLG mutation. These data support the hypothesis that peanut allergy develops through transcutaneous sensitization in children with an impaired skin barrier

Addressing the need for an adult allergy clinic in Malta

The incidence of allergy is globally on the increase. Allergology is a relatively new speciality with rapidly growing needs. Many patients have co-existent allergic conditions including asthma, eczema, allergic rhinitis, food and drug allergy. It is recommended internationally that patients suffering from allergic conditions including anaphylaxis are investigated, treated and followed up by an allergy specialist in a safe environment with resuscitation facilitations readily available, especially when certain investigations are performed. This article highlights the importance of the need for such an allergy service for adult patients at Mater Dei Hospital, in patients with new onset or previously undiagnosed allergic conditions as well as transition of care from paediatric services, with the intention of performing specialist investigations, providing optimal expert management and expert to allergy sufferers locally whilst improving patients’ quality of life. A multidisciplinary team approach would further improve this service.peer-reviewe

What proportion of adult allergy referrals to secondary care could be dealt with in primary care by a GP with special interest?

Background: The concept of a General Practitioner with Special Interest (GPwSI) was first proposed in the 2000 National Health Service Plan, as a way of providing specialised treatment closer to the patient’s home and reducing hospital waiting times. Given the patchy and inadequate provision of allergy services in the UK the introduction of GPwSIs might reduce the pressure on existing specialist services. Objectives: This study assessed what proportion of referrals to a specialist allergy clinic could be managed in a GPwSI allergy service with a predefined range of facilities and expertise (accurate diagnosis and management of allergy; skin prick testing; provision of advice on allergen avoidance; ability to assess suitability for desensitisation). Methods: 100 consecutive GP referrals to a hospital allergy clinic were reviewed to determine whether patients could be seen in a community-based clinic led by a general practitioner with special interest (GPwSI) allergy. The documentation relating to each referral was independently assessed by three allergy specialists. The referrals were judged initially on the referral letter alone and then re-assessed with the benefit of information summarised in the clinic letter, to determine whether appropriate triage decisions could be made prospectively. The proportion of referrals suitable for a GPwSI was calculated and their referral characteristics identified. Results: 29 % referrals were judged unanimously appropriate for management by a GPwSI and an additional 30 % by 2 of the 3 reviewers. 18 % referrals were unsuitable for a GPwSI service because of the complexity of the presenting problem, patient co-morbidity or the need for specialist knowledge or facilities. Conclusions and clinical relevance: At least a quarter, and possibly half, of allergy referrals to our hospital-based service could be dealt with in a GPwSI clinic, thereby diversifying the patient pathway, allowing specialist services to focus on more complex cases and reducing the waiting time for first appointments

A recipe for myositis : nuclear factor κB and nuclear factor of activated T-cells transcription factor pathways spiced up by cytokines

Nuclear factor κB (NF-κB) is a well-known pro-inflammatory transcription factor that regulates the expression of the tissue’s immune-active components, which include cytokines, chemokines and adhesion molecules. In addition, the versatile nuclear factor of activated T-cells (NFAT) family of transcription factors plays a crucial role in the development and function of the immune system, integrating calcium signaling with other signaling pathways. NF-κB and NFAT share many structural and functional characteristics and likely regulate gene expression through shared enhancer elements. This review describes recent research data that has led to new insights into the involvement of NFκB- and NFAT-mediated pathways in the different idiopathic inflammatory myopathies. The general activation of NF-κB p65 in blood vessel endothelium, seems to flag down inflammatory cells that subsequently accumulate mostly at perimysial sites in dermatomyositis. The joint activation of p65 and NFAT5 in myofibers specifically at perifascicular areas reflects the characteristic tissue damage pattern observed in that particular subgroup of patients. In immune cells actively invading nonnecrotic muscle fibers in polymyositis and sporadic inclusion body myositis on the other hand, p65 activation is an important aspect of their cytotoxic and chemoattactant properties. In addition, both transcription factor families are generally upregulated in regenerating muscle fibers as components of the differentiation process. It can be concluded that the two transcription factor families function in close relationship with each other, representing two-edged swords for muscle disease: on the one hand promoting cell growth and regeneration, while on the other hand actively participating in inflammatory cell damage. In this respect, cytokines function as important go-betweens at the crossroads of the pathways. Beyond NF-κB and NFAT, many fascinating winding roads relevant to inflammatory myopathy disease management still lie ready for the exploring