A rare case of lysozyme-induced anaphylaxis in a child with egg allergy.

We report an unusual case of anaphylaxis induced by the lysozyme-containing over-the-counter-drug Lysopaine®, which contains 20 mg lysozyme hydrochloride and 1.5 mg cetylpyridinium chloride, in a 9-year-old child with allergy to hen's egg as well as multiple IgE-mediated food allergies. The involvement of lysozyme was confirmed by positive skin prick tests for Lysopaine® and the presence of specific IgE against lysozyme. Our case highlights the importance of properly educating allergic patients to recognize allergens, even minor ones. Despite the presence of lysozyme in various food and drug products, it is not necessarily perceived as an allergenic protein by patients with egg allergy, and the labeling may be misleading, thereby exposing patients to potentially severe reactions.

The association between environmental greenness and the risk of food allergy: A population-based study in Melbourne, Australia.

BACKGROUND: While exposure to environmental greenness in childhood has shown mixed associations with the development of allergic disease, the relationship with food allergy has not been explored. We investigated the association between exposure to environmental greenness and challenge-confirmed food allergy in a large population-based cohort. METHODS: The HealthNuts study recruited 5276 12-month-old infants in Melbourne, Australia, who underwent skin prick testing to peanut, egg, and sesame; infants with a detectable wheal underwent food challenges to determine food allergy status. Environmental greenness was estimated using the normalized difference vegetation index (NDVI) for five buffer zones around the infant's home address: at the home, 100 m, 500 m, 800 m, and 1600 m radial distances. Environmental greenness was categorized into 3 tertiles and mixed effects logistic regression models quantified the association between greenness and the risk of food allergy, adjusting for confounding and accounting for clustering at the neighborhood level. RESULTS: NDVI data were available for n = 5097. For most buffer zones, medium and high greenness, compared to low greenness, was associated with an increased risk of peanut allergy (eg, 100 m tertile 2 aOR 1.89 95% CI 1.22-2.95, tertile 3 aOR 1.78 95% CI 1.13-2.82). For egg allergy, the effect sizes were smaller (100 m tertile 2 aOR 1.52 95% CI 1.16-1.97, tertile 3 aOR 1.38 95% CI 1.05-1.82). Socioeconomic status (SES) modified the association between greenness and peanut allergy, but not egg allergy; associations were apparent in the low SES group but not in the high SES group (p for interaction 0.08 at 100 m). Air pollution (PM2.5) also modified the associations between environmental greenness and food allergy, with associations present in high air pollution areas but not low (p for interaction at 100 m 0.05 for peanut and 0.06 for egg allergy.) CONCLUSION: Increased exposure to environmental greenness in the first year of life was associated with an increased risk of food allergy. Increased greenness may correlate with higher pollen levels which may trigger innate immune responses skewing the immune system to the Th2-dependent allergic phenotype; additionally, some pollen and food allergens are cross-reactive. Given the mixed data on greenness and other allergies, the relationship appears complex and may also be influenced by confounding variables outside those that were measured in this study.

Atypical food protein-induced enterocolitis syndrome in children: Is IgE sensitisation an issue longitudinally?

BACKGROUND: Food Protein-Induced Enterocolitis Syndrome (FPIES) is a clinically well-characterised, non-Immunoglobulin E (IgE)-mediated food allergy syndrome, yet its rare atypical presentation remains poorly understood. OBJECTIVE: Aim of this study was to present the 10-year experience of a referral centre highlighting the atypical FPIES cases and their long-term outcome. METHODS: FPIES cases were prospectively evaluated longitudinally in respect of food outgrowth and developing other allergic diseases with or without concomitant IgE sensitisation. RESULTS: One hundred subjects out of a total of 14,188 referrals (0.7%) were identified. At presentation, 15 patients were found sensitised to the offending food. Fish was the most frequent eliciting food, followed by cow's milk and egg. Tolerance acquisition was earlier for cow's milk, followed by egg and fish, while found not to be protracted in atypical cases. Resolution was not achieved in half of the fish subjects during the 10-year follow-up time. Sensitisation to food was not related to infantile eczema or culprit food, but was related to sensitisation to aeroallergens. In the long-term evaluation, persistence of the FPIES or aeroallergen sensitisation was significantly associated with an increased hazard risk of developing early asthma symptoms. CONCLUSION: Sensitisation to food was related neither to eczema or culprit food nor to tolerance acquisition but rather to the development of allergic asthma through aeroallergen sensitisation. In addition to an IgE profile at an early age, FPIES persistence may also trigger mechanisms switching FPIES cases to a T-helper 2 cells immune response later in life, predisposing to atopic respiratory symptoms; albeit further research is required.

Altered immune cell profiles and impaired CD4 T-cell activation in single and multi-food allergic adolescents.

BACKGROUND: Approximately 5% of adolescents have a food allergy, with peanut and tree nut allergies the most common. Having two or more food allergies in adolescence also doubles the risk of any adverse food reaction, and is associated with increased dietary and social burden. Investigations of immune function in persistently food allergic children are rare. OBJECTIVE: In the present study, we aimed to investigate the immune mechanisms that underlie food allergy in adolescence. METHODS: We used high-dimensional flow cytometry, unsupervised computational analysis and functional studies to comprehensively phenotype a range of non-antigen-specific immune parameters in a group of well-characterized adolescents with clinically defined single peanut allergy, multi-food allergy and aged-matched non-food allergic controls. RESULTS: We show that food allergic adolescents have higher circulating proportions of dendritic cells (p = .0084, FDR-adjusted p = .087, median in no FA: 0.63% live cells, in FA: 0.93%), and higher frequency of activated, memory-like Tregs relative to non-food allergic adolescents (p = .011, FDR-adjusted p = .087, median in no FA: 0.49% live cells, in FA: 0.65%). Cytokine profiling revealed that CD3/CD28 stimulated naïve CD4 T cells from food allergic adolescents produced less IL-6 (p = .0020, FDR-adjusted p = .018, median log2 fold change [stimulated/unstimulated] in no FA: 3.03, in FA: 1.92) and TNFα (p = .0044, FDR-adjusted p = .020, median in no FA: 9.16, in FA: 8.64) and may secrete less IFNγ (p = .035, FDR-adjusted p = .11, median in no FA: 6.29, in FA: 5.67) than naïve CD4 T cells from non-food allergic controls. No differences between clinical groups were observed for LPS-stimulated monocyte secretion of cytokines. CONCLUSIONS: These results have important implications for understanding the evolution of the immune response in food allergy throughout childhood, revealing that dendritic cell and T-cell signatures previously identified in early life may persist through to adolescence.

Pros and cons of pre-emptive screening programmes before peanut introduction in infancy.

Peanut allergy is an important public health concern and causes substantial psychosocial comorbidity. Although fatal anaphylaxis is rare (occurring at 0·03-0·3 per million person-years in the general population), peanuts are one of the most frequent causes of food allergy mortality. The Learning Early About Peanut study transformed prevention of peanut allergy by showing that early introduction of peanut into the diet of children at high risk (ie, those with an egg allergy or severe eczema) reduced the relative risk of peanut allergy at age 5 years by 81%. Following publication of this study, the US National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, convened an expert panel, which recommended that, for infants with severe eczema or egg allergy, health professionals should strongly consider evaluation with peanut-specific serological IgE or skin prick test (or both) and, if necessary, an oral food challenge before peanut introduction. In the USA, depending on test results, peanut-containing foods are recommended to be introduced from age 4-6 months in infants with severe eczema or egg allergy. Early introduction to peanuts is also advocated for children with either mild to moderate or no eczema, and in children who are not allergic to egg, but without screening before peanut introduction. However, the NIAID addendum guidelines contrast with other international approaches that do not advocate for allergy screening at a population level before introducing peanuts into infants' diets. In this Review, we evaluate the advantages and disadvantages of a pre-emptive screening approach before the early introduction of peanuts in infants at high risk of peanut allergy.

Yellow Fever Vaccination In EGG-Allergic Children.

Yellow fever vaccine contains ovalbumin, and guidelines for vaccination of egg allergic patients vary widely. We present our experience of administering yellow fever vaccine to 11 egg-allergic children, including 3 with anaphylaxis to egg, in 2 Australian tertiary pediatric hospitals. There was variation in the vaccination protocols used; however, all patients were successfully vaccinated and no serious adverse events were reported.

Food-induced anaphylaxis in infancy compared to preschool age: A retrospective analysis.

OBJECTIVE: Little is known regarding food anaphylaxis in infancy. We aimed to describe specificities of food anaphylaxis in infants (≤12 months) as compared to preschool children (1-6 years). METHODS: We conducted a retrospective study of all food anaphylaxis cases recorded by the Allergy Vigilance Network from 2002 to 2018, in preschool children focusing on infants. RESULTS: Of 1951 food anaphylaxis reactions, 61 (3%) occurred in infants and 386 (20%) in preschool children. Two infants had two anaphylaxis reactions; thus, we analyzed data among 59 infants (male: 51%; mean age: 6 months [SD: 2.9]); 31% had a history of atopic dermatitis, 11% of previous food allergy. The main food allergens were cow's milk (59%), hen's egg (20%), wheat (7%) and peanut (3%) in infants as compared with peanut (27%) and cashew (23%) in preschool children. Anaphylaxis occurred in 28/61 (46%) cases at the first cow's milk intake after breastfeeding discontinuation. Clinical manifestations were mainly mucocutaneous (79%), gastrointestinal (49%), respiratory (48%) and cardiovascular (21%); 25% of infants received adrenaline. Hives, hypotension and neurologic symptoms were more likely to be reported in infants than in preschool children (P = .02; P = .004; P = .002, respectively). Antihistamines and corticosteroids were more often prescribed in preschool children than in infants (P = .005; P = .025, respectively). CONCLUSION: Our study found that in infants presenting with their first food allergy, in a setting with a high rate of infant formula use, the most predominant trigger was cow's milk. As compared to older preschool children, hives, hypotonia and hypotension were more likely to be reported in infants. We believe that this represents a distinct food anaphylaxis phenotype that can further support developing the clinical anaphylaxis criteria in infants.

Prevention of food allergy.

Primary prevention and secondary prevention in the context of food allergy refer to prevention of the development of sensitization (i.e., the presence of food-specific immunoglobulin E (IgE) as measured by skin-prick testing and/or laboratory testing) and sensitization plus the clinical manifestations of food allergy, respectively. Until recently, interventions that target the prevention of food allergy have been limited. Although exclusive breast-feeding for the first 6 months of life has been a long-standing recommendation due to associated health benefits, recommendations regarding complementary feeding in infancy have significantly changed over the past 20 years. There now is evidence to support early introduction of peanut into the diet of infants with egg allergy, severe atopic dermatitis, or both diagnoses, defined as high risk for peanut allergy, to try to prevent development of peanut allergy. Although guideline-based recommendations are not available for early introduction of additional allergenic foods, this topic is being actively studied. There is no evidence to support additional dietary modification of the maternal or infant diet for the prevention of food allergy. Similarly, there is no conclusive evidence to support maternal avoidance diets for the prevention of food allergy.

Acquisition of tolerance to egg and peanut in African food-allergic children with atopic dermatitis.

BACKGROUND: There are no previous data on tolerance development in children with atopic dermatitis (AD) and concomitant food allergy in low- and middle-income settings. OBJECTIVES: To determine the rate of tolerance acquisition to egg and peanut 5 years after diagnosing food allergies in South African (SA) children with AD, and to explore factors influencing tolerance acquisition. METHODS: Five years after first diagnosing food allergy in 37 SA children with egg and/or peanut allergy, they were reassessed for their allergies by questionnaire, skin-prick tests (SPTs) and ImmunoCAP-specific IgE (sIgE) tests (Thermo Fisher Scientific/Phadia, Sweden) to egg white, ovomucoid, peanut and Arachis hypogaea allergen 2 (Ara h 2), and incremental food challenges. RESULTS: Eighteen of 25 originally egg-allergic patients and 19 of 24 originally peanut-allergic children were followed up at a median age of 8 years and 3 months and 9 years and 6 months, respectively. A high percentage of children (72.2%) outgrew their egg allergy, and 15.8% outgrew their peanut allergy. Allergic comorbidity remained high, with asthma increasing over time, and AD remaining moderate in severity in the cohort overall. At diagnosis, sIgE egg white ≤9.0 kU/L and sIgE ovomucoid ≤2.0 kU/L were associated with tolerance development to egg 5 years later. At follow-up, sIgE egg white ≤0.70 kU/L, sIgE ovomucoid ≤0.16 kU/L, SPT egg-white extract ≤1 mm and SPT fresh egg ≤5 mm were associated with tolerance. At diagnosis, sIgE Ara h 2 ≤1.7 kU/L and SPT peanut ≤10 mm were associated with tolerance development to peanut 5 years later. At follow-up, sIgE peanut ≤0.22 kU/L, sIgE Ara h 2 ≤0.18 kU/L and SPT peanut ≤5.5 mm were associated with tolerance. CONCLUSIONS: Egg allergy was outgrown in 72.2% and peanut allergy in 15.8% of SA children 5 years after diagnosis of AD. This is in keeping with findings derived from studies in higher socioeconomic settings, and can help to guide the counselling of patients with allergies to these foods of high nutritional value.

Propofol use in children with allergies to egg, peanut, soybean or other legumes.

Propofol is the most commonly administered intravenous agent for anaesthesia in children. However, there are concerns that the emulsified preparation may not be safe in children with an allergy to egg, peanut, soybean or other legumes. We conducted a retrospective study of children with immunologically confirmed egg, peanut, soybean or legume allergy and who underwent general anaesthesia at Princess Margaret Hospital for Children between 2005 and 2015. We extracted details regarding allergy diagnosis, each anaesthetic administered and any adverse events or signs of an allergic reaction in the peri-operative period. A convenience sample of patients without any known food allergies was identified from our prospective anaesthesia research database and acted as a control group. We identified 304 food-allergic children and 649 procedures where propofol was administered. Of these, 201 (66%) had an egg allergy, 226 (74%) had a peanut allergy, 28 (9%) had a soybean allergy and 12 (4%) had a legume allergy. These were compared with 892 allergy-free patients who were exposed to propofol. In 10 (3%) allergy patients and 124 (14%) allergy-free patients, criteria for a possible allergic reaction were met. In nine of the food-allergic children and in all the controls valid non-allergic explanations for the clinical symptoms were found. One likely mild allergic reaction was experienced by a child with a previous history of intralipid allergy. We conclude that genuine serious allergic reaction to propofol is rare and is not reliably predicted by a history of food allergy.

Trajectories of class-switching-related egg and cow's milk allergen-specific immunoglobulin isotype formation and its modification by eczema with low- and high-affinity immunoglobulin E during early infancy.

INTRODUCTION: Allergen-specific immunoglobulin isotype formation associated with immunoglobulin class-switching during the lactation period is the immunological background for food allergy in infants. We analyzed the serial changes in the production of feeding type-related egg- and milk-specific immunoglobulin isotypes from birth to 6 months of age with or without eczema in 84 infants. METHODS: Allergen-specific immunoglobulin G1 (IgG1), IgG2, IgG3, IgG4, IgA, and IgE levels of hen's egg and bovine milk were measured in cord blood and blood samples from infants at 2, 4, and 6 months of age by the densely carboxylated protein microarray. RESULTS: Formula and mixed feeding were associated with a rapid increase in cow's milk allergen-specific immunoglobulins and feeding type-related significant differences in casein-specific immunoglobulin levels were detected. Breast and mixed feeding were associated with slow but significant increase in ovalbumin-specific IgG1 and IgE levels, but not other immunoglobulins. We found two different immunoglobulin isotype formation at 6 months of age with low- or high-affinity IgE against ovalbumin. One isotype formation pattern had relatively high ovalbumin-specific IgG1 levels, detectable IgG2, and low-affinity IgE, while the other had low ovalbumin-specific IgG1 levels, undetectable IgG2, and high levels of high-affinity IgE. The incidence of eczema was significantly higher in the latter pattern (84.6%), compared with the remaining infants (42.2%). CONCLUSIONS: Feeding practice-related allergen sensitization and immunoglobulin isotype formation were identified during the lactation period. The development of eczema during the lactation period could potentially modify the immunoglobulin isotype formation with high levels of high-affinity IgE.

Palmar hyperlinearity in early childhood atopic dermatitis is associated with filaggrin mutation and sensitization to egg.

BACKGROUND/OBJECTIVES: Palmar hyperlinearity is a typical clinical feature of Filaggrin gene (FLG) null mutations. There are reports of FLG mutations and allergic sensitization; however, reports on the relationship between palmar hyperlinearity to sensitization are limited. This study aimed to examine the association between palmar hyperlinearity and sensitization in atopic dermatitis (AD) children. METHODS: This cross-sectional, case-control study included children ˂ 6 years old with moderate-severe AD whose parents consented for mutation analysis and photographic documentation. Each child underwent genotyping to detect the eight most prevalent FLG mutations in the Japanese population: R501X, 3321delA, S1695X, Q1701X, S2554X, S2889X, S3296X, and K4022X. Clinical features and parameters including egg-specific IgE were examined, and palm photographs were evaluated by 12 trained dermatologists blinded to genotyping results. RESULTS: Of the 57 patients (age range, 2 months to 5 years; median, 22 months), 16 were heterozygotes and three were compound heterozygotes. Palmar hyperlinearity, as recognized by more than two-thirds of dermatologists, was significantly associated with FLG mutation (P = 0.002, OR = 6.98, 95% CI = 2.1-23.7), and this association was observed especially in children over 2 years. Cross-shaped crease of the thenar eminence, as known in previous reports, also demonstrated significant correlation with FLG mutation. When the children were divided according to the presence or absence of palmar hyperlinearity, the egg white-specific IgE was significantly higher in the hyperlinearity group (55.9 vs 18.3 IU/mL, P < 0.05). CONCLUSIONS: Palmar hyperlinearity indicates possible inherited barrier abnormalities of the skin in early childhood. Its identification may help to predict a more accurate prognosis, such as sensitization.

Recommendations for the use of propofol in egg-allergic patients

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Are both early egg introduction and eczema treatment necessary for primary prevention of egg allergy?

The Learning Early About Peanut Allergy (LEAP) study proved that early introduction of peanut significantly prevented the development of peanut allergy. However, in regard to similar attempts to prevent egg allergy through early egg introduction, the Prevention of Egg Allergy in High-risk Infants with Eczema (PETIT) study is the only randomized intervention trial to show a statistically significant effect. Meta-analysis of those studies indicated that neither the total amount nor pretreatment of egg showed any effect on egg allergy at the age of 12 months. However, raw egg powder resulted in a significantly higher prevalence of allergic reactions at initial introduction, whereas use of boiled egg was much safer. The prevalence of atopic dermatitis/eczema at introduction of egg correlated significantly with the subsequent prevalence of allergic reactions at initial introduction. In addition, the prevalence of egg allergy in the late introduction group correlated significantly with the prevalence of atopic dermatitis at introduction, even when the atopic dermatitis was proactively treated with a topical corticosteroid ointment. It is definitely true that the number of trials and number of participants in each trial are insufficient for drawing firm conclusions, especially regarding the optimal dose, raw versus boiled, when to start, and for whom to intervene. Therefore we propose various studies that should be performed to generate stronger data and conclusions. However, on the basis of the most recent results, we postulate that simultaneous intervention by both early boiled egg introduction and eczema treatment is probably indispensable for primary prevention of egg allergy.

The frequency of allergic reactions to the triple viral vaccine in 94 patients with egg allergy / Frecuencia de las reacciones alérgicas a la vacuna triple viral en pacientes con alergia al huevo

Introduction: Vaccination is the most effective public health intervention of all times, reducing the death and morbidity rates derived from multiple infectious diseases. In many cases, the administration and reception of vaccines is delayed due to the fear of allergic reactions; this is frequent among patients with allergy to egg who need the triple viral vaccine. Objective: To evaluate the frequency of reactions after the administration of triple viral vaccine (Measles, Mumps and Rubella, MMR) in an egg-allergic population. Materials and methods: We conducted a multi-center retrospective study (2014-2016) including patients with egg allergy who visited an allergology center and required the administration of the triple viral vaccine. Results: A total of 94 patients met the selection criteria. From these patients, 68.2% had cutaneous symptoms, 22.3% had an anaphylactic reaction, 5.3% had gastrointestinal symptoms, and 4.2% had respiratory egg-related symptoms. Regardless of the severity of their reaction to egg, all patients received the triple viral vaccine and in 100% of the cases, it was well tolerated. Conclusion: Although egg allergy is common in childhood, the risk of allergic reactions during the MMR vaccination in this population was similar to that in the general population, therefore, its use should not be deferred even in patients with a history of severe egg-related allergic reactions.

Introducción. La vacunación es la intervención en salud pública más efectiva de todos los tiempos, pues reduce la mortalidad y la morbilidad de múltiples enfermedades infecciosas. En muchas ocasiones, la aplicación de las vacunas se retrasa por el temor a las reacciones alérgicas, lo cual es frecuente entre los pacientes con alergia al huevo que requieren la vacuna triple viral (rubeola-sarampión-parotiditis).Objetivo. Evaluar la frecuencia de reacciones después de la aplicación de la vacuna triple viral en una población alérgica al huevo.Materiales y métodos. Se hizo un estudio retrospectivo multicéntrico (2014-2016) de pacientes con alergia al huevo que acudieron a centros de alergología de Medellín y requerían la aplicación de la vacuna triple viral.Resultados. Noventa y cuatro pacientes cumplían los criterios de selección; 68,2 % de ellos presentaba síntomas cutáneos al consumir huevo; 22,3 %, reacción anafiláctica; 5,3 %, síntomas gastrointestinales, y 4,2 %, síntomas respiratorios. Independientemente de la gravedad de su reacción al huevo, todos los pacientes recibieron la vacuna triple viral y la toleraron bien.Conclusión. Aunque la alergia al huevo es frecuente en la edad infantil, el riesgo de reacciones alérgicas después de aplicar la vacuna triple viral en esta población fue similar al de la población general, por lo que no se debe diferir su aplicación, incluso en pacientes con antecedentes de reacciones graves al huevo.

Early-life sensitization to hen's egg predicts asthma and rhinoconjunctivitis at 14 years of age.

BACKGROUND: Sensitization to both inhalant and food allergens has been shown to be risk factors for development of asthma and rhinoconjunctivitis (RC). However, few studies have addressed the role of transient or persistent IgE sensitization to specific allergens in early life for later development of allergic diseases. The aim of this study was to explore the association between transient and persistent sensitization in early life and the development of asthma and RC at 6 and 14 years. METHODS: The Danish Allergy Research Center (DARC) cohort is a prospective non-interventional birth cohort study comprising 562 children. For the purpose of this study, we examined a subgroup of the original cohort with specific IgE measured at, at least 3 of 4 follow-ups between 3 and 18 months of age (n = 366). Multiple logistic regression models were used to investigate the association between transient and persistent early-life sensitization to groups of and to individual allergens and asthma and RC at 6 and 14 years compared to a reference group with no sensitization. RESULTS: Both transient early-life sensitization and persistent early-life sensitization to cow's milk or hen's egg proteins were associated with asthma (aOR 3.99[1.41-11.32] and 5.95[1.78-19.92]) and RC (aOR 2.94[1.19-7.28] and 6.18[1.86-20.53]) at 14 years, this association being driven mainly by sensitization to hen's egg. Transient early-life sensitization to house dust mite (HDM) had increased risk of asthma (aOR 3.80[1.17-12.41]) at 14 years. CONCLUSIONS: Early transient IgE sensitization and persistent IgE sensitization to hen's egg were associated with asthma and RC at 14 years. Furthermore, sensitization to HDM was associated with asthma at 14 years.