Dianne E. Campbell

A global survey of changing patterns of food allergy burden in children

While food allergies and eczema are among the most common chronic non-communicable diseases in children in many countries worldwide, quality data on the burden of these diseases is lacking, particularly in developing countries. This 2012 survey was performed to collect information on existing data on the global patterns and prevalence of food allergy by surveying all the national member societies of the World Allergy Organization, and some of their neighbouring countries. Data were collected from 89 countries, including published data, and changes in the health care burden of food allergy. More than half of the countries surveyed (52/89) did not have any data on food allergy prevalence. Only 10% (9/89) of countries had accurate food allergy prevalence data, based on oral food challenges (OFC). The remaining countries (23/89) had data largely based on parent-reporting of a food allergy diagnosis or symptoms, which is recognised to overestimate the prevalence of food allergy. Based on more accurate measures, the prevalence of clinical (OFC proven) food allergy in preschool children in developed countries is now as high as 10%. In large and rapidly emerging societies of Asia, such as China, where there are documented increases in food allergy, the prevalence of OFC-proven food allergy is now around 7% in pre-schoolers, comparable to the reported prevalence in European regions. While food allergy appears to be increasing in both developed and developing countries in the last 10–15 years, there is a lack of quality comparative data. This survey also highlights inequities in paediatric allergy services, availability of adrenaline auto-injectors and standardised National Anaphylaxis Action plans. In conclusion, there remains a need to gather more accurate data on the prevalence of food allergy in many developed and developing countries to better anticipate and address the rising community and health service burden of food allergy.

Consensus Communication on Early Peanut Introduction and the Prevention of Peanut Allergy in High-risk Infants

The purpose of this brief communication is to highlight emerging evidence to existing guidelines regarding potential benefits of supporting early, rather than delayed, peanut introduction during the period of complementary food introduction in infants. This document should be considered as interim guidance based on consensus among the following organizations: American Academy of Allergy, Asthma & Immunology; American Academy of Pediatrics; American College of Allergy, Asthma & Immunology; Australasian Society of Clinical Immunology and Allergy; Canadian Society of Allergy and Clinical Immunology; European Academy of Allergy and Clinical Immunology; Israel Association of Allergy and Clinical Immunology; Japanese Society for Allergology; Society for Pediatric Dermatology; and World Allergy Organization. More formal guidelines regarding early-life, complementary feeding practices and the risk of allergy development will follow in the next year from the National Institute of Allergy and Infectious Diseases – sponsored Working Group and the European Academy of Allergy and Clinical Immunology.

Immune Response to Infection with Mycobacterium ulcerans

ABSTRACT Mycobacterium ulcerans is a slow-growing, acid-fast bacillus that causes chronic necrotizing skin ulcers known as Buruli ulcers. Previously reported information on immunity to this mycobacterium is limited. We examined immune responses to M. ulcerans and M. bovis BCG in patients with M. ulcerans disease and in 20 healthy control subjects (10 tuberculin test positive and 10 tuberculin test negative). Cell-mediated immunity was assessed by stimulating peripheral blood mononuclear cells (PBMC) with whole mycobacteria and then measuring PBMC proliferation and the production of gamma interferon (IFN-γ). Humoral immunity was assessed by immunoblotting. PBMC from all subjects showed significantly greater proliferation and IFN-γ production in response to stimulation with living mycobacteria compared with killed cells. However, PBMC from subjects with past or current M. ulcerans disease showed significantly reduced proliferation and production of IFN-γ in response to stimulation with live M. ulcerans or M. bovis than PBMC from healthy, tuberculin test-positive subjects (P < 0.001) and showed results in these assays comparable to those of tuberculin test-negative subjects (P > 0.2). Serum from 9 of 11 patients with M. ulcerans disease, but no control subject, contained antibodies to M. ulcerans. The results indicate that patients with M. ulcerans infection mount an immune response to M. ulcerans as evidenced by antibody production, but they demonstrate profound systemic T-cell anergy to mycobacterial antigens. These findings may explain some of the distinct clinical and pathological features of M. ulcerans-induced disease.

Reviews and feature articleConsensus communication on early peanut introduction and the prevention of peanut allergy in high-risk infants

The purpose of this brief communication is to highlight emerging evidence to existing guidelines regarding potential benefits of supporting early, rather than delayed, peanut introduction during the period of complementary food introduction in infants. This document should be considered as interim guidance based on consensus among the following organizations: American Academy of Allergy, Asthma & Immunology, American Academy of Pediatrics, American College of Allergy, Asthma & Immunology, Australasian Society of Clinical Immunology and Allergy, Canadian Society of Allergy and Clinical Immunology, European Academy of Allergy and Clinical Immunology, Israel Association of Allergy and Clinical Immunology, Japanese Society for Allergology, Society for Pediatric Dermatology, and World Allergy Organization. More formal guidelines regarding early-life, complementary feeding practices and the risk of allergy development will follow in the next year from the National Institute of Allergy and Infectious Diseases-sponsored Working Group and the European Academy of Allergy and Clinical Immunology.

Monogenic mutations differentially affect the quantity and quality of T follicular helper cells in patients with human primary immunodeficiencies

BACKGROUND Follicular helper T (TFH) cells underpin T cell-dependent humoral immunity and the success of most vaccines. TFH cells also contribute to human immune disorders, such as autoimmunity, immunodeficiency, and malignancy. Understanding the molecular requirements for the generation and function of TFH cells will provide strategies for targeting these cells to modulate their behavior in the setting of these immunologic abnormalities. OBJECTIVE We sought to determine the signaling pathways and cellular interactions required for the development and function of TFH cells in human subjects. METHODS Human primary immunodeficiencies (PIDs) resulting from monogenic mutations provide a unique opportunity to assess the requirement for particular molecules in regulating human lymphocyte function. Circulating follicular helper T (cTFH) cell subsets, memory B cells, and serum immunoglobulin levels were quantified and functionally assessed in healthy control subjects, as well as in patients with PIDs resulting from mutations in STAT3, STAT1, TYK2, IL21, IL21R, IL10R, IFNGR1/2, IL12RB1, CD40LG, NEMO, ICOS, or BTK. RESULTS Loss-of-function (LOF) mutations in STAT3, IL10R, CD40LG, NEMO, ICOS, or BTK reduced cTFH cell frequencies. STAT3 and IL21/R LOF and STAT1 gain-of-function mutations skewed cTFH cell differentiation toward a phenotype characterized by overexpression of IFN-γ and programmed death 1. IFN-γ inhibited cTFH cell function in vitro and in vivo, as corroborated by hypergammaglobulinemia in patients with IFNGR1/2, STAT1, and IL12RB1 LOF mutations. CONCLUSION Specific mutations affect the quantity and quality of cTFH cells, highlighting the need to assess TFH cells in patients by using multiple criteria, including phenotype and function. Furthermore, IFN-γ functions in vivo to restrain TFH cell-induced B-cell differentiation. These findings shed new light on TFH cell biology and the integrated signaling pathways required for their generation, maintenance, and effector function and explain the compromised humoral immunity seen in patients with some PIDs.

Allergic Reactions to Propofol in Egg-Allergic Children

BACKGROUND: Egg and/or soy allergy are often cited as contraindications to propofol administration. Our aim was to determine whether children with an immunoglobulin (Ig)E-mediated egg and/or soy allergy had an allergic reaction after propofol use. METHODS: We performed a retrospective case review over an 11-year period (1999–2010) of children with IgE-mediated egg and/or soy allergy who had propofol administered to them at the Childrens Hospital Westmead, Sydney. RESULTS: Twenty-eight egg-allergic patients with 43 propofol administrations were identified. No child with a soy allergy who had propofol was identified. Twenty-one children (75%) were male, the median age at anesthesia was 2.4 years (range, 1–15 years), and the presence of other atopic disease was common (eczema 61%, asthma 32%, peanut allergy 43%). Most children (n = 19, 68%) had a history of an IgE-mediated clinical reaction to egg with evidence of a significantly positive egg white skin prick test (SPT) reaction (≥7 mm). Two of these had a history of egg anaphylaxis. The remaining children (n = 9, 32%) had never ingested egg because of significantly positive SPT (≥7 mm). All SPTs to egg were performed within 12 months of propofol administration. There was one nonanaphylactic immediate allergic reaction (n = 1 of 43, 2%) that occurred 15 minutes after propofol administration in a 7-year-old boy with a history of egg anaphylaxis and multiple other IgE-mediated food allergies (cows milk, nut, and sesame). SPT to propofol was positive at 3 mm. No other egg-allergic child reacted to propofol. CONCLUSIONS: Despite current Australian labeling warnings, propofol was frequently administered to egg-allergic children. Propofol is likely to be safe in the majority of egg-allergic children who do not have a history of egg anaphylaxis.

Food allergy: Is strict avoidance the only answer?

It is an immunological paradigm that avoidance of food allergen may reduce the risk or prevent immunological reactions and conversely that a greater exposure increases the magnitude of the immune response. Consequently, food allergen avoidance has been recommended to reduce the risk of sensitization in infants and to prevent clinical reactions in children with positive skin prick tests (SPT). In the latter setting, it is hoped that avoidance may either promote or at least not retard the development of tolerance. Animal studies, however, have demonstrated that tolerance to food allergens may be induced by either large (high zone tolerance) or small (low zone tolerance) doses, whereas doses in between may actually stimulate immune responses. In this review, we discuss whether strict allergen avoidance is always the most appropriate strategy for preventing or managing IgE‐mediated food allergy.

Safety of food challenges to extensively heated egg in egg-allergic children: a prospective cohort study

Many children with IgE‐mediated allergy to egg can tolerate egg in baked foods. However, the clinical characteristics and severity of reactions of egg‐allergic children who react to baked egg at open food challenge (OFC) are not well defined.

A randomized trial of egg introduction from 4 months of age in infants at risk for egg allergy

Background: Epidemiologic evidence suggests delayed introduction of egg might not protect against egg allergy in infants at risk of allergic disease. Objective: We sought to assess whether dietary introduction of egg between 4 and 6 months in infants at risk of allergy would reduce sensitization to egg. Methods: We conducted a randomized controlled trial in infants with at least 1 first‐degree relative with allergic disease. Infants with a skin prick test (SPT) response to egg white (EW) of less than 2 mm were randomized at age 4 months to receive whole‐egg powder or placebo (rice powder) until 8 months of age, with all other dietary egg excluded. Diets were liberalized at 8 months in both groups. The primary outcome was an EW SPT response of 3 mm or greater at age 12 months. Results: Three hundred nineteen infants were randomized: 165 to egg and 154 to placebo. Fourteen infants reacted to egg within 1 week of introduction (despite an EW SPT response <2 mm at entry) and were unsuitable for intervention. Two hundred fifty‐four (83%) infants were assessed at 12 months of age. Loss to follow‐up was similar between groups. Sensitization to EW at 12 months was 20% and 11% in infants randomized to placebo and egg, respectively (odds ratio, 0.46; 95% CI, 0.22–0.95; P = .03, χ2 test). The absolute risk reduction was 9.8% (95% CI, 8.2% to 18.9%), with a number needed to treat of 11 (95% CI, 6–122). Levels of IgG4 to egg proteins and IgG4/IgE ratios were higher in those randomized to egg (P < .0001 for each) at 12 months. There was no effect on the proportion of children with probable egg allergy (placebo, 13; egg, 8). Conclusions: Introduction of whole‐egg powder into the diets of high‐risk infants reduced sensitization to EW and induced egg‐specific IgG4 levels. However, 8.5% of infants randomized to egg were not amenable to this primary prevention.

Baked egg food challenges – clinical utility of skin test to baked egg and ovomucoid in children with egg allergy

Many children with IgE‐mediated egg allergy can tolerate products containing extensively heated (baked) egg. Aside from food challenge, there are no tests which reliably predict tolerance to baked egg in egg‐allergic individuals.