Immunotherapy: a new horizon for egg allergy?

The prevalence of IgE-mediated food allergy (FA) in childhood varies from 6% to 8% in the first year of life compared to 1% to 2% in adults. In contrast to adults, FA in childhood, often part of the "allergic march", resolves in more than 85% of children, especially those with hypersensitivity to cow's milk and egg. This paper explains the rationale for continuing care for childhood FA and describes how children should be monitored for resolution/persistence of FA. A clinical, multidisciplinary approach and management algorithm based on relevant, peer-reviewed original research articles and reviews using the keywords anaphylaxis, atopic eczema, children, milk allergy, double-blind placebo-controlled food challenge, egg allergy, epinephrine, failure to thrive, food allergy, food challenge, food hypersensitivity, immunoglobulin E, nutrition, natural history, paediatrics, peanut allergy, prevalence, psychosocial factors, quality of life, radioallergosorbent test, and tolerance from years 1966 to 2003 in MEDLINE. Additional studies were identified from article reference lists. A combination of outcome measures, a multidisciplinary approach involving a dietitian and allergy nurse specialist, and a management algorithm are useful tools in clinical management. Prospective studies of non-selected children, optimally from birth cohorts, are needed to evaluate the effects of such management programmes regarding FA in childhood.

Early life innate immune signatures of persistent food allergy

Staden U, Rolinck-Werninghaus C, Brewe F, Wahn U, Niggemann B, Beyer K. Allergy. 2007;62(11):1261–1269 PURPOSE OF THE STUDY. To evaluate the efficacy of oral tolerance induction as a treatment for cow's milk and egg allergies. STUDY POPULATION. Forty-seven children aged 0.6 to 12.9 years with positive double-blind, placebo-controlled food challenges to milk or hen's egg were included in this German study. Children with severe eczema were excluded. METHODS. Subjects were randomly assigned to specific oral tolerance induction or continued avoidance. Treatment involved home escalation over at least 67 days from a dose of 1 drop of cow's milk to 250 mL or from 5 mg of lyophilized hen egg powder to 3500 mg. Subjects continued home dosing for a median of 21 months total, after which time they underwent a secondary period of avoidance for 2 months followed by a food challenge. RESULTS. At follow-up challenge, 9 (36%) of 25 children in the specific-oral-tolerance-induction group showed permanent tolerance, 3 (12%) of 25 were tolerant with regular intake, 4 (16%) of 25 were partial responders, and 9 (36%) of 25 did not complete the treatment because of adverse effects. In the control group, 7 (35%) of 20 children were tolerant at the study end. Allergen-specific IgE levels decreased in children who developed tolerance both in the control (P < .05) and treatment (P < .001) groups. CONCLUSIONS. Specific oral tolerance induction may be a valid treatment option for patients with persistent food allergy. However, only a minority of patients had evidence of persistent tolerance once treatment was stopped, with some unable to tolerate the therapy and others seeming to be only transiently desensitized. REVIEWER COMMENTS. Allergen-specific immunotherapy with injected extracts has proven too dangerous to be a viable treatment method for food allergy. Sublingual or oral immunotherapy, as described here, is a promising alternative to strict avoidance. Although one third of the patients in this study had to withdraw because of adverse effects, the remaining patients were able to incorporate the allergen into their diet at some level. This treatment modality is highly promising, but it is still experimental, carries the potential for significant risk, and requires close monitoring by experienced physicians. Several studies of oral and sublingual immunotherapy for food allergy are ongoing in the United States and Europe.

Oral immunotherapy for egg allergy in children.

Objective: Cow’s milk allergy is the most frequent food allergy in childhood. Delayed diagnosis may cause a number of systemic dysfunctions, while incorrect diagnosis may result in deficient nutrition of the mother and the child. As in other types of allergies, food allergy is also a growing problem in recent years. Our aim was to determine the characteristics of our patients allergic to cow’s milk, and see if there was an increasing trend. Material and Methods: The study was of retrospective and cross-sectional design. Patient data were collected from Pediatric Allergy Department patient files. Cases of food allergy were reviewed and patients fulfilling the criteria of cow’s milk allergy were included in the study. Results: A total of 105 cases with cow’s milk allergy out of 264 food allergies who were followed up between 2003-2011 were investigated. Most of the patients were under 2 years of age (78.1%), were males (62.9%) and presented with a history of allergy (79.1%). IgE mediated cases constituted the majority (75.2%). More than half of the patients admitted in 2010 and 2011. This was mostly due to the increased number of patients less than twelve months of age (p=0.015). Most frequently involved system was skin (67.5%) and multisystem involvement was 15.7% Conclusion: A detailed history is the key element of diagnosing cow’s milk allergy. There is a considerable number of cases within the first year of life which may present with different signs and symptoms. Although not a life threatening situation, correct diagnosis is vital as nutrition is a key component in the development and growth of child.

<b><i>Background:</i></b> The minimal dose for oral immunotherapy (OIT) tolerance is unknown. We investigated the efficacy and safety of low-dose OIT with 1/32 of the volume of a whole egg. <b><i>Methods:</i></b> Thirty-three children (aged ≥5 years) with egg allergies confirmed by oral food challenge against 1/32 of a heated whole egg (194 mg of egg protein) were enrolled. The OIT group ingested a scrambled egg once a day. The volume was gradually increased up to a maximum of 1/32 of a heated whole egg. Egg consumption was completely absent in the control group. <b><i>Results:</i></b> There were no significant differences in background between the OIT and control groups. Respectively, 71% (15/21) and 0% (0/12) of the patients in the OIT and control groups exhibited sustained unresponsiveness to 1/32 of a whole egg 2 weeks after stopping OIT after 12 months (<i>p</i> &lt; 0.001); 33% (7/21) and 0% (0/12; <i>p</i> = 0.032), respectively, showed sustained unresponsiveness to 1/2 of a whole egg. Egg white- or ovomucoid-specific IgE levels in the OIT group were significantly lower than at baseline after 12 months. Egg white- or ovomucoid-specific IgG as well as IgG4 levels in the OIT group were significantly higher than baseline levels after 1, 3, 6, and 12 months. Adverse allergic reactions were rare, and most symptoms were mild. <b><i>Conclusions:</i></b> Low-dose OIT induced sustained unresponsiveness to 1/32 and 1/2 of a whole egg, with no severe symptoms. To improve food allergies, continuous intake of small amounts of these foods may be as effective as the consumption of larger quantities.

Prevalence of Food Sensitization and Food Allergy in Children Across Europe

Relevance. Food allergy is one of the most common chronic diseases in children. Toll-like receptors may be unique in the development of food allergies due to their expression by intestinal epithelial and dendritic cells. Objective. The aim of this study was to investigate the relationship between the rs4696480 polymorphism in TLR2 and the presence of food allergy in children with atopic dermatitis. Material and methods. The study included 103 patients with atopic dermatitis and 84 healthy children. Polymorphism genotyping was performed in the group of patients and the control group using real-time PCR. Food sensitization was determined by presence sIgE to food allergens by the immunochemiluminescent method using an ImmunoCAP 100 (Thermo Fisher Scientific Inc., Phadia, Sweden). The presence of food allergy was determined by a detailed clinical history and review of clinical records. Results. In the subgroup of children with food allergies, 9 children had the AA genotype, 7 patients had the heterozygous variant, and 3 children had the TT genotype. Among patients without food allergy, 20 patients had the AA genotype, 39 were heterozygotes, and 25 had the TT genotype. The OR assessment demonstrated that the AA genotype of the rs4696480 polymorphism is reliably associated with the development of food allergy in children with atopic dermatitis, OR=2,880 (1,0271-8,0757). Conclusion. The rs4696480 polymorphism in TLR2 gene is associated with the development of food allergy in Ukrainian children with atopic dermatitis.

Gastroesophageal reflux disease (GERD) and food allergy are frequent disorders of childhood. The purpose of this study was to determine the frequency of food allergy in children with refractory GERD. A total of 151 children resistant to pharmacologic GERD treatment underwent skin prick test, specific immunoglobulin E, eosinophil count, atopy patch test (APT), and oral food challenge, and were then divided into three groups according to the results of oral milk challenge and allergy work-up: group A1, positive oral milk challenge and positive IgE-mediated allergy test; group A2, positive milk challenge and negative IgE-mediated allergy test; and group B, negative oral milk challenge and negative allergy tests. There were 35, 30 and 86 patients in group A1, group A2 and group B, respectively. A total of 28 of 35 patients in group A1 had cow's milk allergy and the other seven patients had egg allergy. APT positivity was more common in group A2. Endoscopic esophagitis was observed in six group A1 patients and in four group A2 patients. Bloody stools, atopic dermatitis and recurrent wheezing episodes were significantly more common in group A1 than in group A2 and group B (P < 0.001, for both). Cow's milk allergy was observed frequently in children resistant to pharmacologic GERD treatment. Combined skin prick and specific IgE tests, APT and oral food challenge is essential for avoidance of unnecessary elimination diet.

Cracking the egg: An insight into egg hypersensitivity

IntroductionEgg allergy is the most common food allergy in children but recent studies have shown persistence or delayed resolution into adolescence. As there is currently no effective long-term treatment, definitive...

Food allergy in Sri Lanka – A comparative study

It is unclear why some children develop food allergy. The EuroPrevall birth cohort was established to examine regional differences in the prevalence and risk factors of food allergy in European children using gold-standard diagnostic criteria. The aim of this report was to describe pre-, post-natal and environmental characteristics among the participating countries. In nine countries across four major European climatic regions, mothers and their newborns were enrolled from October 2005 through February 2010. Using standardized questionnaires, we assessed allergic diseases and self-reported food hypersensitivity of parents and siblings, nutrition during pregnancy, nutritional supplements, medications, mode of delivery, socio-demographic data and home environmental exposures. A total of 12,049 babies and their families were recruited. Self-reported adverse reactions to food ever were considerably more common in mothers from Germany (30%), Iceland, United Kingdom, and the Netherlands (all 20-22%) compared with those from Italy (11%), Lithuania, Greece, Poland, and Spain (all 5-8%). Prevalence estimates of parental asthma, allergic rhinitis and eczema were highest in north-west (Iceland, UK), followed by west (Germany, the Netherlands), south (Greece, Italy, Spain) and lowest in central and east Europe (Poland, Lithuania). Over 17% of Spanish and Greek children were exposed to tobacco smoke in utero compared with only 8-11% in other countries. Caesarean section rate was highest in Greece (44%) and lowest in Spain (<3%). We found country-specific differences in antibiotic use, pet ownership, type of flooring and baby's mattress. In the EuroPrevall birth cohort study, the largest study using gold-standard diagnostic criteria for food allergy in children worldwide, we found considerable country-specific baseline differences regarding a wide range of factors that are hypothesized to play a role in the development of food allergy including allergic family history, obstetrical practices, pre- and post-natal environmental exposures.

IgE-mediated egg allergy is a common childhood food allergy affecting about 1-2% of 2-yr-old children. Egg avoidance is the mainstay of treatment for egg allergy; however, it is unclear what type of dietary advice parents of children with egg allergy receive and to what extent this dietary advice is adhered to. This study aimed to assess: (i) the type and source of dietary advice parents receive in a tertiary hospital setting, (ii) how closely parents adhere to advice given, (iii) what patient characteristics influenced adherence to diet and (iv) whether strict adherence to dietary advice was an identifiable factor in whether children outgrew their egg allergy. In 2006, a questionnaire was sent to 261 parents of children seen in a tertiary paediatric allergy clinic in 2003 and diagnosed with egg allergy which included 84 children who had undergone an in-hospital open oral egg challenge during this time period (2003-2006). Questions included demographic data, details of egg allergy, dietary avoidance and attainment of unrestricted egg ingestion. Of 199 questionnaires confirmed received, 167 were returned (84%). The mean age of the cohort was 6.6 yr with an average of 5.5 yr of follow-up since the first reaction. Sixty-eight percent of subjects reported avoidance of all food containing egg all the time. Forty-seven percent of the children had been accidentally exposed to egg. The severity of the initial reaction did not appear to influence adherence to an advised diet. Of the 84 children who underwent in-hospital open egg challenges, 57 children were able to ingest egg without clinical reaction and were classified as having outgrown their egg allergy. These children did not differ from those who were challenge positive to egg in terms of either the dietary advice they received or the degree to which they had undertaken strict avoidance of egg. In addition, children who had outgrown their egg allergy did not differ from those who remained egg-allergic on in-hospital challenge in terms of either the frequency of accidental ingestion or the severity of initial reaction. Strict avoidance of egg and accidental ingestion of egg did not appear to influence the acquisition of tolerance.

Cow's milk protein allergy (CMPA) is the most frequent food allergy in early childhood. For those infants requiring breastmilk substitutes, formulas with extensively hydrolyzed proteins (EHF), should be the treatment of choice. As there are limited data showing the progression of initial symptoms in infants newly diagnosed with CMPA who are treated with EHF with added synbiotics, the main objective of this study was to evaluate the resolution of symptoms in said infants after 4 weeks of treatment. As a secondary objective this study aimed to assess the impact of the treatment on the family's quality of life. observational, longitudinal, prospective, and multicentric real-world evidence study. The intervention phase (EHF with synbiotics) lasted 28 days and was completed by 65 patients. Treating physicians registered child´s anthropometry, Infant Gastrointestinal Symptoms Questionnaire (IGSQ-13) and CoMiSS (Cow´s Milk Allergy Symptoms Score) both at baseline and after 28 days of treatment. During treatment, caregivers reported child´s regurgitation and stools, PO-SCORAD (Patient Oriented Scoring of Atopic Dermatitis) and FAQL-PB (Family Quality of Life-Parental Burden). Data were collected using Google Forms and analyzed through the STATA program. 95.4% of the patients showed an improvement or disappearance of the overall initial symptoms after 4 weeks of treatment. Gastrointestinal symptoms improved or disappeared in 92% of patients (p < 0.05) while dermatological symptoms improved or disappeared in 87.5% of patients (p < 0.05). The median CoMiSS at baseline was 9, with 21 patients exceeding the cut-off point of 12. After 4 weeks of treatment, the median dropped to 3, and no patient exceeded the 12-cut-off point (p = 0.000). At baseline, patients had a PO-SCORAD of 11.5 (interquartile range 1-23) that went to 1.0 (interquartile range 1-6) at day 28 (p = 0.000). The treatment diminished stool frequency (p < 0.05), improved stool consistency (p = 0.004) and decreased the frequency of regurgitation in infants with CMPA (p = 0.01). The percentage of patients who no longer had any episode of regurgitation increased from 11% to 31% on day 28 (p = 0.003). At baseline, 13% of patients cried more than 3 h per day, while at day 28 that percentage dropped to 3% (p = 0.03). An improvement in the infants' sleep pattern was also appreciated with the treatment. At study onset, 56% of the families reported feeling very overwhelmed, a percentage that dropped to 17% after 28 days of treatment (p < 0.05). The small percentage of families who did not feel overwhelmed at study onset (17%), grew to 43% on day 28 (p < 0.05). The use of an EHF with synbiotics for the management of infants diagnosed with or suspected to have CMPA suggested a good safety profile, an adequate infant growth, and improvement of overall, gastrointestinal, and dermatological symptoms. It also suggested a lower daily frequency of regurgitations and stools, and an improvement in stool consistency, sleeping pattern, and quality of life of the infant and his family.