Oral immunotherapy in children with IgE-mediated hen's egg allergy: Follow-ups at 2.5 and 7 years.

BACKGROUND: The present report was a follow-up investigation at 2.5- and 7-year intervals of a previous study of 20 children with moderate-to-severe immunoglobulin E (IgE) mediated hen's egg (HE) allergy who received oral immunotherapy (OIT) with raw HE. The study design of the previous study divided the 20 subjects into two groups of 10 each: (1) group 1, the OIT group (OIT-G), and, (2) group 2, an age-matched control group (C-G). In that study, 8 of 10 of the children in the OIT-G were successfully desensitized, one child was partially desensitized, and desensitization failed in one child. The aims of the present study were to evaluate the long-term effectiveness and safety profile of OIT with raw HE, and to assess the course and prognostic value of skin-prick tests (SPT) and serum-specific HE-IgEs in this study population. METHODS: Of the 20 children who were recalled, 2 dropped out, which left 18 to be evaluated. Information on their HE intake was recorded, and SPTs with HE allergen extracts and with raw and hard-boiled HE were performed. Ovomucoid- and ovalbumin-specific IgE levels were also measured. RESULTS: At the first (2.5-year) and second (7-year) follow-ups, 87.5% of the children in the OIT-G who tolerated raw HE were still tolerant, whereas the children in the C-G were significantly less tolerant. Overall, cutaneous sensitivity to HE significantly decreased after the 6-month desensitization period and at both follow-ups with regard to the OIT-G but not with regard to the C-G. A significant reduction in serum ovomucoid- and ovalbumin-specific IgE levels was seen in both the OIT-G and the C-G. CONCLUSION: Clinical raw HE tolerance induced by OIT persists over time. Negativization of SPTs could be considered a more reliable prognostic indicator of clinical tolerance to raw HE than the reduction in specific-HE IgE levels. Raw-HE OIT would seem to be a promising method to treat HE allergy.

Consensus Conference on Clinical Management of pediatric Atopic Dermatitis.

The Italian Consensus Conference on clinical management of atopic dermatitis in children reflects the best and most recent scientific evidence, with the aim to provide specialists with a useful tool for managing this common, but complex clinical condition. Thanks to the contribution of experts in the field and members of the Italian Society of Pediatric Allergology and Immunology (SIAIP) and the Italian Society of Pediatric Dermatology (SIDerP), this Consensus statement integrates the basic principles of the most recent guidelines for the management of atopic dermatitis to facilitate a practical approach to the disease. The therapeutical approach should be adapted to the clinical severity and requires a tailored strategy to ensure good compliance by children and their parents. In this Consensus, levels and models of intervention are also enriched by the Italian experience to facilitate a practical approach to the disease.

The perception of allergen-specific immunotherapy among pediatricians in the primary care setting.

BACKGROUND: Allergic respiratory diseases are constantly increasing in prevalence. Allergen Immunotherapy (AIT) represent a valuable therapeutic tool as symptomatic and preventative approach, expecially in children. In Italy, primary care pediatricians (PCP) represent the first-line contact and interface for prescription, use and management of AIT. We attempted to evaluate the perception of AIT practice among PCP. METHODS: A questionnaire was built-up, based on literature, guidelines and with the contribution of pediatricians. The questionnaire, including 12 items, was e-mailed to 180 PCP, randomly chosen from mailing lists. The questionnaire explored the personal perception of AIT, the comparison between subcutaneous and sublingual AIT and the overall awareness about the treatment. RESULTS: 130 questionnaires were eligible for analysis. There was a satisfactory knowledge of the characteristics of AIT, its aims and limits, although the positioning of the treatment in guidelines was insufficiently known. Overall, the prescription of AIT made by other specialists was accepted and agreed (78 %). The majority of pediatricians felt that a more intense divulgation and information about AIT would be needed (90 %). CONCLUSION: AIT is in general well known and accepted among PCP, although a more intense divulgation effort is required.

Pollen-induced allergic rhinitis in 1360 Italian children: comorbidities and determinants of severity.

BACKGROUND: Pollen-induced allergic rhinoconjunctivitis (AR) is highly prevalent and rapidly evolving during childhood. General practitioners may not be fully aware of the nature and severity of symptoms experienced by patients and might underestimate the prevalence of moderate or severe disease. Thus, the relevance of early diagnosis and intervention may be overlooked. OBJECTIVES: To investigate the severity of pollen-induced AR and its determinants in Italian children referred to allergy specialists and who had never received specific immunotherapy (SIT). METHODS: Children (age 4-18 yr) affected by pollen-induced AR who had never undergone SIT were recruited between May 2009 and June 2011 in 16 pediatric outpatient clinics in 14 Italian cities. Recruited children's parents answered standardized questionnaires on atopic diseases (International Study of Allergy and Asthma in Childhood, Allergic Rhinitis and its Impact on Asthma, Global Initiative for Asthma). The children underwent skin-prick test (SPT) with several airborne allergens and six food allergens. Information on socio-demographic factors, parental history of allergic diseases, education, perinatal events, breastfeeding, nutrition and environmental exposure in early life was collected through an informatics platform shared by the whole network of clinical centers (AllergyCARD™). RESULTS: Among the 1360 recruited patients (68% males, age 10.5 ± 3.4 yr), 695 (51%) had moderate-to-severe AR, 533 (39%) asthma, and 325 (23.9%) oral allergy syndrome (OAS). Reported onset of pollen-induced AR was on average at 5.3 ± 2.8 yr, and its mean duration from onset was 5.2 ± 3.3 yr. Only 6.2% of the patients were pollen-monosensitized, and 84.9% were sensitized to ≥3 pollens. A longer AR duration was significantly associated with moderate-to-severe AR symptoms (p 0.004), asthma (p 0.030), and OAS comorbidities (p < 0.001). CONCLUSIONS: This nationwide study may raise awareness of the severity of pollen-induced AR among Italian children who have never received pollen SIT. The strong association between pollen-induced AR duration and several markers of disease severity needs replication in longitudinal studies, while suggesting that countrywide initiatives for earlier diagnosis and intervention should be planned.

Oral food desensitization: the BACH proposal for the very gradual reintroduction of a food.

PURPOSE OF REVIEW: The common treatment of IgE-mediated food allergy is to avoid the offending item and educating patients on appropriate emergency measures. Recently, attempts to gain food tolerance with oral administration of increasing doses of the offending food have become frequent. Desensitization procedures are risky and safety is a priority. Their success depends on the individual allergic characteristics and the modality of food administration. RECENT FINDINGS: Most schedules adopted in the desensitization protocols are empiric and not regular, as requirements of safety would require. SUMMARY: Some oral food desensitization schedules were compared in order to verify whether the increments between doses were regular. Through a mathematic formula adopted by the musicians to tune instruments in the 17th Century, including Bach, I describe a method to calculate an increment factor by which a schedule of food administration that ensures an absolutely constant increment between doses can be achieved. This method can prove useful for every situation in which a gradual dose increment is needed (food, drugs in an experimental setting, specific immunotherapy with inhalants or venom insect allergens). All calculations can be done also without a computer, and this is particularly important if modern technologies are not available, such as in developing countries.I propose calling this method 'Building an Allergen-augmentation Curve Harmoniously (BACH)'.

Oral food desensitization in children with IgE-mediated hen's egg allergy: a new protocol with raw hen's egg.

BACKGROUND: Hen's egg allergy affects young children and can cause severe allergic reactions. Avoidance results in dietary limitations and can affect the quality of life, especially in cases where potentially life-threatening reactions exist. Our objective was to desensitize children with moderate-severe IgE-mediated hen's egg allergy over a 6-month period, by introducing increasing and very gradual daily doses of raw hen's egg in order to enable the children to assume 25ml of this food, or to induce tolerance to the highest possible dose. The protocol foresaw the egg reintroduction in the home setting. METHODS: In this randomized, controlled open study, 20 hen's egg allergic children (10 in the active group) were admitted. A convincing history or a positive double-blind placebo-controlled food challenge confirmed the diagnosis. Oral desensitization was performed with increasing doses starting from 0.27 mg of hen's egg proteins (1 drop of raw hen's egg diluted 1:100). We adopted an original, mathematically calculated protocol in order to ensure a constant, daily increment of doses. RESULTS: 8/10 children (80%) in the active group achieved the daily intake of 25ml over a 6-month period. One child (10%) could tolerate up to 2ml/day while another child (10%) failed the desensitization. Six months after enrolment only 2 children in the control group (20%) could tolerate hen's egg. CONCLUSIONS: We successfully desensitized 8/10 children with IgE-mediated hen's egg allergy in a 6-month period. The partial outcome in the child who could tolerate 2ml/day reduced the risk of severe reactions after unnoticed introduction of egg. A regular protocol that ensures a daily constant increase of doses helps to reduce possible adverse events, thus improving safety and effectiveness.

Oral desensitisation with food is food-specific and protein-specific.

The avoidance of food(s) is the main therapeutic approach to food allergy. Nevertheless, orally- or sublingually-administered food allergens have gained attention and a number of food-allergic children can tolerate gradually increasing amounts of cow's milk and hen's egg. Our purpose is to show that oral desensitisation with food is an allergen-specific therapeutic approach and for this, we describe 4 illustrative children with IgE-mediated food allergy. The first was allergic to cow's milk and hen's egg, the second to cow's milk, hen's egg and fish. Both underwent oral desensitisation to both cow's milk and hen's egg. The third child was allergic to cow's milk, hen's egg and fish and underwent oral desensitisation with cow's milk. The last child was allergic to raw but not to cooked/boiled hen's egg and underwent the oral desensitisation with hen's egg. The first 2 children reached the clinical tolerance to cow's milk after the cow's milk oral desensitisation, but reached the hen's egg tolerance only after the hen's egg oral desensitisation. Moreover, the second child did not tolerate fish after being desensitised to both cow's milk and hen's egg. The third child tolerated cow's milk, but not hen's egg and fish, at the end of the cow's milk oral desensitisation. The fourth child could tolerate the previously not tolerated raw hen's egg after the oral desensitisation with raw hen's egg. In conclusion, we indicate that oral desensitisation with food is allergen specific. The induction of the clinical tolerance to one food is not followed by the tolerance to the other food(s) that the patient is allergic to. To obtain a double or multiple food tolerance, separate desensitisation protocols, one for each food, have to be carried out. Oral desensitisation with food discriminates between raw and cooked proteins.

Association of Filaggrin loss-of-function-mutations with atopic dermatitis and asthma in the Early Treatment of the Atopic Child (ETAC) population.

Many candidate gene studies for atopic dermatitis (AD) and associated phenotypes have been conducted so far, but replication of significant results has been a major problem. Two loss of function polymorphisms FLG R501X- and 2282del4, in the Filaggrin (FLG) gene encoding for an epidermal barrier protein were recently identified. They were reported to be predisposing factors for AD and concomitant asthma. Several groups confirmed the initial results in independent populations. The aim of this study is to further investigate the importance of these FLG variants in the development of AD and subsequent asthma symptoms in pre-school children, we investigated children and parents of the Early Treatment of the Atopic Child (ETAC)-trial. We genotyped 496 children and 488 parents of the ETAC population for the two FLG variants, evaluating an association by family based analysis (transmission disequilibrium test). We found a highly significant association of the FLG null variants R501X- and 2282del4 with AD (combined genotype p < 0.0001) and asthma (combined genotype p < 0.0001). The replication and its statistical significance underlines the importance of the FLG polymorphisms and the importance of the skin barrier function in the development of AD and subsequent asthma.

IL13 variants are associated with total serum IgE and early sensitization to food allergens in children with atopic dermatitis.

Increased total and specific serum immunoglobulin E (IgE) levels are common characteristics of atopic diseases and their basal production is proposed to be under strong genetic control. Interleukin 13 (IL13) variants have been consistently associated with total serum IgE levels in white populations with a strongest association in non-atopics. The aim of this study was to test the IL13 p.R130Q and c.1-1111C>T variants in children with atopic dermatitis (AD) for associations with total serum IgE and early sensitization to common food and inhalant allergens and with asthma. We included 453 children with AD [participants of the Early Treatment of the Atopic Child (ETAC) study] that were followed from the age of 12-24 months for 3 yr. Total and specific IgE were determined at four time points. We genotyped the IL13 p.R130Q and c.1-1111C>T variants by melting curve analysis. In children up to 4 yr of age, the 130Q allele was related to slightly higher total IgE levels compared to heterozygotes and 130R homozygotes. More importantly, both IL13 variants were significantly associated with sensitization to food allergens, with most significant results for sensitization to egg (p = 0.0001). Although early sensitization to hen's egg represents a strong risk factor for subsequent sensitization to inhalant allergens and asthma, the investigated IL13 variants were not associated with these phenotypes at the age of 48-60 months. In summary IL13 variants contribute to elevated levels of total serum IgE in young atopic children and are strongly associated with sensitization to food allergens, particularly to hen's egg. These findings suggest that IL13 variants play a major role not only in non-cognate but also in allergen specific IgE synthesis.

Oral desensitization in children with immunoglobulin E-mediated cow's milk allergy--follow-up at 4 yr and 8 months.

Until now, the basic treatment for food allergy has been to avoid the offending item. This approach is difficult in the case of common foods and in the case where there is a risk of severe reaction after consuming the offending food, even inadvertently. This is the follow-up of a previous study aimed at desensitizing 21 children with immunoglobulin E (IgE)-mediated cow's milk (CM) allergy. This protocol was totally or partially successful in 85% of cases, but failed in the remaining 15%. Our aims were to study the long-term effectiveness and safety of oral CM desensitization, and the prognostic value of Skin Prick Test (SPT) and specific serum CM IgE. The 21 children were called back (one dropped out). The allergic history and other information on CM intake over the last 4-5 yr were recorded. Children underwent SPT, and end-point SPT, with casein and alpha-lactoalbumin. Specific CM IgE was also measured. At follow-up, 14/20 children totally (n = 13, 65%) or partially (n = 1, 5%) tolerated CM. None of the recalled children reported use of emergency care. SPT positivity to casein and/or alpha-lactoalbumin decreased significantly (p < 0.01), and all the negative SPT referred to the tolerant children. Cutaneous sensitivity to both casein and alpha-lactoalbumin (end-point SPT) significantly decreased after the 6-month desensitization period of the previous study (p < 0.001), but did not decrease significantly at follow-up. A significant reduction of serum-specific CM IgE was also observed (p < 0.05). Clinical tolerance induced by oral CM desensitization persists in time. Negativization of SPT and reduction of specific CM IgE could be considered prognostic indicators of CM tolerance. Oral CM desensitization seems to be a promising method to treat CM food allergy. This protocol is time-consuming but offers the advantage that it can be performed at home. This methodology must only be used by trained staff.

Prevalence of latex allergy and evaluation of some risk factors in a population of atopic children.

The aims of our study were to evaluate (1) the prevalence of natural rubber latex (NRL) allergy in an unselected population of atopic children; (2) the diagnostic efficacy of skin prick tests (SPTs) with latex extracts; (3) the correlation between positive SPTs to latex and risk factors such as atopy, fruit allergy, history of surgery cares or dental cares. We randomly enrolled 151 unselected atopic and 59 nonatopic children who underwent SPTs with common inhalant and food allergens, and SPTs with two different latex extracts. A clinical history concerning allergic history, symptoms after contact with latex objects or after ingestion of fruits or vegetables, dental and surgical treatments was obtained. Six of the 151 atopic children were positive to latex SPTs, but only one out of 59 nonatopic children was positive to latex SPTs. Concerning risk factors, 86% of children with SPT positive to latex were atopic, 71.4% had a clinical history of surgery, and none of them had undergone dental or orthodontic treatments. The prevalence of NRL sensitization in our unselected population of atopic children was 3.9%, but the prevalence of NRL allergy was 2.6%. Concerning NRL allergy, the sensitivity and the specificity of SPTs with latex extracts are high (1.00 and 0.98, respectively), as well as negative predicting value (1.00); the positive predictive value is low (0.70). We conclude that atopy, surgical treatments, and sensitization to foods cross-reacting with NRL are important risk factors for NRL sensitization. We have no data concerning dental or orthodontic cares.