Jonathan O'b Hourihane

Standardization of food challenges in patients with immediate reactions to foods – position paper from the European Academy of Allergology and Clinical Immunology

At present, the double blind placebo controlled foodchallenge(DBPCFC)representstheonlywaytoestablishorruleoutanadversereactiontoafoodinolderchildrenand adults, whereas an open challenge controlled bytrained personnel is sufficient in infants and youngchildren (1). The challenge procedure is not, however,C.Bindslev-Jensen

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.

Assessment of quality of life in children with peanut allergy

Children with a peanut allergy (PA) are faced with food and social restrictions due to the potentially life‐threatening nature of their disease, for which there is no cure or treatment. This inevitably impacts upon their quality of life (QoL). QoL of 20 children with PA and 20 children with insulin‐dependent diabetes mellitus (IDDM) was measured using two disease‐specific QoL questionnaires (higher scores correspond to a poorer QoL). One questionnaire was designed by us and the other was adapted from the Vespid Allergy QoL questionnaire. We gave subjects cameras to record how their QoL is affected over a 24‐h period. Response rates for both questionnaires were 100%. Mean ages were 9.0 and 10.4 years for PA and IDDM subjects, respectively. Children with a PA reported a poorer quality of life than children with IDDM: mean scores were 54.85 for PA subjects and 46.40 for diabetics (p = 0.004) in questionnaire 1 and 54.30 and 34.50 (p≤0.001) in questionnaire 2. PA children reported more fear of an adverse event and more anxiety about eating, especially when eating away from home. Photographs fell into seven common categories: food, management, environment, away from home, physical activities, restaurant and people. Most photographs related to food and management issues and revealed difficulties for both groups regarding food restrictions. PA subjects felt more threatened by potential hazards within their environment, felt more restricted by their PA regarding physical activities, and worried more about being away from home. However, they felt safe when carrying epinephrine kits and were positive about eating at familiar restaurants. The QoL in children with PA is more impaired than in children with IDDM. Their anxiety may be considered useful in some situations, promoting better adherence to allergen avoidance advice and rescue plans.

Diversity of Bifidobacteria within the Infant Gut Microbiota

Background The human gastrointestinal tract (GIT) represents one of the most densely populated microbial ecosystems studied to date. Although this microbial consortium has been recognized to have a crucial impact on human health, its precise composition is still subject to intense investigation. Among the GIT microbiota, bifidobacteria represent an important commensal group, being among the first microbial colonizers of the gut. However, the prevalence and diversity of members of the genus Bifidobacterium in the infant intestinal microbiota has not yet been fully characterized, while some inconsistencies exist in literature regarding the abundance of this genus. Methods/Principal Findings In the current report, we assessed the complexity of the infant intestinal bifidobacterial population by analysis of pyrosequencing data of PCR amplicons derived from two hypervariable regions of the 16 S rRNA gene. Eleven faecal samples were collected from healthy infants of different geographical origins (Italy, Spain or Ireland), feeding type (breast milk or formula) and mode of delivery (vaginal or caesarean delivery), while in four cases, faecal samples of corresponding mothers were also analyzed. Conclusions In contrast to several previously published culture-independent studies, our analysis revealed a predominance of bifidobacteria in the infant gut as well as a profile of co-occurrence of bifidobacterial species in the infant’s intestine.

Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy

Background IgE-mediated peanut allergy is a complex trait with strong heritability, but its genetic basis is currently unknown. Loss-of-function mutations within the filaggrin gene are associated with atopic dermatitis and other atopic diseases; therefore, filaggrin is a candidate gene in the etiology of peanut allergy. Objective To investigate the association between filaggrin loss-of-function mutations and peanut allergy. Methods Case-control study of 71 English, Dutch, and Irish oral food challenge–positive patients with peanut allergy and 1000 non peanut-sensitized English population controls. Replication was tested in 390 white Canadian patients with peanut allergy (defined by food challenge, or clinical history and skin prick test wheal to peanut ≥8 mm and/or peanut-specific IgE ≥15 kUL−1) and 891 white Canadian population controls. The most prevalent filaggrin loss-of-function mutations were assayed in each population: R501X and 2282del4 in the Europeans, and R501X, 2282del4, R2447X, and S3247X in the Canadians. The Fisher exact test and logistic regression were used to test for association; covariate analysis controlled for coexistent atopic dermatitis. Results Filaggrin loss-of-function mutations showed a strong and significant association with peanut allergy in the food challenge–positive patients (P = 3.0 × 10−6; odds ratio, 5.3; 95% CI, 2.8-10.2), and this association was replicated in the Canadian study (P = 5.4 × 10−5; odds ratio, 1.9; 95% CI, 1.4-2.6). The association of filaggrin mutations with peanut allergy remains significant (P = .0008) after controlling for coexistent atopic dermatitis. Conclusion Filaggrin mutations represent a significant risk factor for IgE-mediated peanut allergy, indicating a role for epithelial barrier dysfunction in the pathogenesis of this disease.

Peanut allergy in relation to heredity, maternal diet, and other atopic diseases: results of a questionnaire survey, skin prick testing, and food challenges.

Abstract Objectives: To determine rates of other atopic manifestations in people with peanut allergy and the prevalence of such allergy in their families. Design: A survey of people with self reported peanut allergy and people referred by their general practitioner for suspected peanut allergy; survey and skin testing of 50 children with reported peanut allergy and their available first degree relatives. Subjects: 622 adults and children with reported, suspected, or known peanut allergy. Main outcome measures: Prevalence of peanut allergy and other allergies in the families of people with peanut allergy. Results: 622 valid completed questionnaires were returned out of the 833 questionnaires dispatched (74.7%). All forms of atopy were both more common in successive generations (P<0.0001) and more common in maternal than paternal relatives (P<0.0001). Peanut allergy was reported by 0.1% (3/2409) of grandparents, 0.6% (7/1213) of aunts and uncles, 1.6% (19/1218) of parents, and 6.9% (42/610) of siblings. Consumption of peanuts while pregnant or breast feeding was more common among mothers of probands aged </=5 years than mothers of probands aged >5 years (P<0.001). Age of onset correlated inversely with year of birth (r = -0.6, P<0.001). Skin prick testing of 50 children with reported peanut allergy and their families: 7 probands (14%) had a negative result for peanut. Peanut allergy was refuted by food challenge in all those tested (5/7). No parent and 13% (5/39) of siblings had a positive result on skin prick testing for peanut. Two of these siblings had negative challenge with peanuts. The prevalence of peanut allergy in siblings is therefore 3/39 (7%). Conclusions: Peanut allergy is more common in siblings of people with peanut allergy than in the parents or the general population. Its apparently increasing prevalence may reflect a general increase of atopy, which is inherited more commonly from the mother. Peanut allergy is presenting earlier in life, possibly reflecting increased consumption of peanut by pregnant and nursing mothers. Key messages The apparent epidemic of peanut allergy is a reflection of the general increase in atopic diseases and increased case identification The age of onset of peanut allergy is decreasing, possibly secondary to increased consumption by mothers and by infants early in life Peanut allergy affects 7% of siblings of people with peanut allergy but only 1.3% of the general population

An evaluation of the sensitivity of subjects with peanut allergy to very low doses of peanut protein: A randomized, double-blind, placebo-controlled food challenge study☆☆☆★

BACKGROUND The minimum dose of food protein to which subjects with food allergy have reacted in double-blind, placebo-controlled food challenges is between 50 and 100 mg. However, subjects with peanut allergy often report severe reactions after minimal contact with peanuts, even through intact skin. OBJECTIVE We sought to determine whether adults previously proven by challenge to be allergic to peanut react to very low doses of peanut protein. METHODS We used a randomized, double-blind, placebo-controlled food challenge of 14 subjects allergic to peanuts with doses of peanut ranging from 10 microg to 50 mg, administered in the form of a commercially available peanut flour. RESULTS One subject had a systemic reaction to 5 mg of peanut protein, and two subjects had mild objective reactions to 2 mg and 50 mg of peanut protein, respectively. Five subjects had mild subjective reactions (1 to 5 mg and 4 to 50 mg). All subjects with convincing objective reactions had short-lived subjective reactions to preceding doses, as low as 100 microg in two cases. Five subjects did not react to any dose up to 50 mg. CONCLUSION Even in a group of well-characterized, highly sensitive subjects with peanut allergy, the threshold dose of peanut protein varies. As little as 100 microg of peanut protein provokes symptoms in some subjects with peanut allergy.

Clinical characteristics of peanut allergy

Background Current clinical advice regarding peanut allergy is based on small series of patients.

Resolution of peanut allergy: case-control study

Abstract Objectives: To determine whether there are any differences between children who remain mildly or moderately allergic to peanut and children with similar histories but a negative reaction on challenge with peanut. Design: Case-controls matched for age and sex. Setting: Childrens day wards in two teaching hospitals. Intervention: Open food challenge with peanut. Subjects: 15 children with resolved peanut allergy (resolvers) and 15 with persistent allergy (persisters). Main outcome measure: Reaction on challenge with peanut, serum total and peanut specific IgE concentrations. Results: The groups had a similar median age at first reaction to peanut (11 months, range 5-38) and similar symptoms. Allergy to other foods was less common in resolvers (2/15) than persisters (9/15) (P=0.02). On skin prick testing with peanut all 13 resolvers tested but only 3/14 persisters had a weal of <6 mm (P<0.0001). Total and peanut specific IgE concentrations did not differ much between the groups. Conclusion: Appropriately trained clinicians must be prepared to challenge preschool children with peanut as some will be tolerant despite a history of reactions to peanut and a positive skin prick test with peanut. Preschool children whose apparent peanut allergy is refuted by food challenge show allergy to other foods less often than those in whom peanut allergy persists. The size of weal on skin prick testing to peanut predicts reactivity but not severity on peanut challenge. Key messages Peanut allergy rarely resolves in older children and adults Skin prick testing with peanut has a high negative predictive value, but some people with positive skin tests do not react to peanut challenge Some preschool children with a convincing history of reaction to peanut may become tolerant of peanut. Such children have fewer other manifestations of atopy than children whose peanut allergy persists Paediatricians must be prepared to undertake peanut challenges or refer children to units that will undertake such challenges

A consensus protocol for the determination of the threshold doses for allergenic foods: how much is too much?

Background While the ingestion of small amounts of an offending food can elicit adverse reactions in individuals with IgE‐mediated food allergies, little information is known regarding these threshold doses for specific allergenic foods. While low‐dose challenge trials have been conducted on an appreciable number of allergic individuals, a variety of different clinical protocols were used making the estimation of the threshold dose very difficult.