Clinical and immunological profile of children aged 5-9 years with persistent egg allergy before oral immunotherapy with egg. A multicenter, randomized controlled trial of the Spanish Society of Pediatric Allergy, Asthma and Clinical Immunology (SEICAP).

BACKGROUND: In children with egg protein allergy (EA), the probability of overcoming the allergy decreases with age, and the possibility of suffering severe adverse reactions as a consequence of dietetic transgressions results in worsened quality of life. One treatment option in such cases is oral immunotherapy (OIT) with foods. METHODS: We present a cohort of children with EA scheduled for OIT with pasteurized raw egg white, describing their clinical and allergic characteristics before the start of OIT. RESULTS: The median age was six years, and 93% of the patients also suffered other allergies (58% asthma and 38.6% allergy to more than two food groups). In the last year, 14.8% had suffered a severe reaction due to dietetic transgression with egg. The median IgE specific of egg white titer was 38.5kU/l. A double-blind placebo-controlled food challenge with cooked egg white was performed, and if the test proved positive, it was repeated with pasteurized raw egg white. The mean symptoms-provoking dose was 1.26g and 0.55g for cooked egg white and raw egg white, respectively. An IgE specific of ovomucoid titer of <2.045kU/l differentiated those patients that tolerated cooked egg white. CONCLUSIONS: OIT with egg is regarded as an option in patients with persistent egg allergy. In the previous challenge test, an IgE specific of ovomucoid titer of <2.045kU/l differentiates those patients that tolerate cooked egg white.

Position document: IgE-mediated allergy to egg protein.

Egg is the food that most often causes allergy in young Spanish children, with an incidence of 2.4-2.6% in the first 2 years of life. The prevalence of sensitisation and allergy to egg is greater in children with allergy to cow's milk and in those suffering atopic dermatitis. The protein component from egg white is the cause of the allergic response in child. The major allergens in egg white are ovomucoid and ovalbumin. Most of the allergic reactions affect the skin, followed by gastrointestinal and respiratory systems. Egg allergy is one of the most common causes of severe anaphylaxis. The diagnosis of egg allergy is based on the existence of a suggestive clinical history, a positive allergy study and the subsequent application of controlled exposure testing, which represents the gold standard for confirming the diagnosis. The treatment of egg allergy is based on the avoidance of egg protein intake. A subgroup of egg-allergic patients are tolerant to cooked egg. In these cases, only uncooked egg must necessarily be avoided. Maintaining a diet with strict egg avoidance is difficult, and transgressions are relatively common. The patient, family, and school environment should receive education and training in the avoidance of egg and in the management of possible allergic reactions. With an avoidance diet, up to 15-20% of children will remain allergic and the severity of the reactions will increase over the years. In these more severe cases of egg-allergy, it becomes more difficult to adhere to the avoidance diet over the years, with a significant decrease in patient quality of life. Oral tolerance induction can be regarded as a therapeutic option for IgE-mediated egg allergy. The anti-IgE, omalizumab, might become another genuine therapeutic option for food allergy, not only to prevent allergic reactions after a contact with egg, but also as a complementary treatment to oral tolerance induction for egg allergy, with the purpose of reducing adverse reactions. The administration of influenza vaccine to children with egg allergy is safe in children that do not manifest severe reactions after egg intake, and in children who tolerate cooked egg. The triple viral vaccine (MMR) can be given to egg-allergic children in their usual vaccination centre, with no added risk. Different medicinal products can be formulated with egg proteins, and therefore should be avoided in children with egg allergy.

Changes in IL-10 and specific antibodies associated to successful Dermatophagoides pteronyssinus immunotherapy in children during the first year of treatment.

BACKGROUND: Allergen-specific immunotherapy (SIT) is a long-term treatment of respiratory allergy. OBJECTIVE: To look for early predictors of the effectiveness of Dermatophagoides pteronyssinus SIT. METHODS: A prospective multi-centre study was carried out in Spain. Children with D. pteronyssinus rhinitis or asthma were invited to participate. The study was divided into times: T0 (recruitment); T1 (inclusion); T2 a-f (immunotherapy times) and T3 (the end of study). Efficacy of SIT was assessed by clinical scores, visual analogue scales (VAS) and lung function tests. We performed D. pteronyssinus skin tests at T1 and T3, and determined specific serum IgE, IgG4 and IL-10 at T1, T2f and T3. Data were analysed using Mann-Whitney and Kruskal-Wallis tests, compared using Wilcoxon and Chi-square tests, and correlated to Spearman test. All tests had a significance level of 0.05. RESULTS: Thirty-eight children completed the study. At T1 all had rhinitis and 34 also had asthma. At T3, 30 patients had improved, six experienced no changes and two worsened. Improvement was associated to FEV1/FVC and VAS improvement; to a reduction in D. pteronyssinus skin prick test; to a progressive increase in serum levels of D. pteronyssinus IgE, and D. pteronyssinus, Der p1 and Der p2 IgG4. IL-10 levels showed an early increase at T2f (the end of initial build-up immunotherapy phase), and then a reduction at T3 (the end of a year of immunotherapy). Improvement associated to an early increase in IL-10 and was correlated with VAS and specific IgG4 evolution.

Oral desensitization as a useful treatment in 2-year-old children with cow's milk allergy.

BACKGROUND: Limited published evidence shows oral desensitization to be a potential intervention option for cow's milk protein (CMPs) allergy. OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of oral desensitization in 2-year-old children with cow's milk allergy, as a treatment alternative to elimination diet. METHODS: A total of 60 children aged 24-36 months with IgE-mediated allergy to CMPs were included in this multi-center study and were randomized into two groups. Thirty children (group A: treatment group) began oral desensitization immediately, whereas the remaining 30 (group B: control group) were kept on a milk-free diet and followed-up for 1 year. RESULTS: After 1-year follow-up period, 90% of the children in group A had become completely tolerant vs. 23% of the children in group B. In group A, cow's milk skin reactivity and serum-specific IgE to milk and casein decreased significantly from the initial assessment, whereas group B showed no significant change after 1 year of follow-up. Twenty-four patients (80%) developed some reaction during the treatment period: 14 children developed moderate reaction (47%) and 10 mild reaction (33%). The most common manifestations were urticaria-angioedema, followed by cough. CONCLUSIONS AND CLINICAL RELEVANCE: In this study, oral desensitization was found to be effective in a significant percentage of 2-year-old children with cow's milk allergy. Oral desensitization appears to be efficacious as an alternative to elimination diet in the treatment of 2-year-old children with cow's milk allergy. The side-effect profile appears acceptable but requires further study.

Tolerancia y eficacia de una fórmula extensamente hidrolizada en lactantes con alergia a proteínas de leche de vaca mediada por IgE. Estudio JUNGLO (I): hidrolizado extenso de caseína / Tolerance and efficacy of an extensively hydrolyzed formula for infants with IgE-mediated cow’s milk protein allergy. JUNGLO study (part I): Extensively hydrolyzed casein formula

Objetivos: El principal objetivo de este estudio fue evaluar la tolerancia de un nuevo hidrolizado de caseína y su eficacia durante un periodo de 3 meses en lactantes diagnosticados de alergia a las proteínas de leche de vaca (APLV) mediada por IgE. Métodos: El estudio forma parte de un ensayo clínico multicéntrico, aleatorizado y doble ciego, que se llevó a cabo en 15 hospitales españoles. En este artículo se presentan los resultados del grupo de tratamiento que recibió un hidrolizado extenso de caseína, comportándose como un estudio observacional. Se incluyeron lactantes diagnosticados de APLV una vez que se confirmó con la titulación de IgE específica, con el fin de comprobar la tolerancia a la nueva fórmula en más del 97% de los niños. La principal variable de estudio fue la tolerancia a la fórmula, y se evaluó mediante una prueba de provocación realizada en el hospital. La evolución de los síntomas clínicos y del crecimiento se evaluó durante un periodo de 3 meses tras la inclusión. Resultados: Se incluyeron 25 niños y 22 niñas. Todos toleraron la introducción de la fórmula de estudio sin reacciones adversas en el primer día, lo que significa que más del 97% de los lactantes toleraron el tratamiento en el momento de su introducción (p= 0,0112). Ocurrieron tres acontecimientos adversos, a los 4, 6 y 10 días de la introducción de la fórmula, que se consideraron posible o probablemente relacionados con la misma, por lo que la tolerancia efectiva fue del 93%. Al cabo de 1 mes de seguimiento, la situación clínica de los lactantes había mejorado, con una disminución del 40,4 al 13% para los síntomas digestivos, y la desaparición total de todos los demás síntomas. El patrón de crecimiento, levemente disminuido al inicio, se normalizó o al menos mejoró a los 3 meses de tratamiento. Conclusiones: El nuevo hidrolizado de caseína se toleró en más del 97% de los lactantes, y mejora los síntomas clínicos de forma rápida en lactantes con APLV mediada por IgE, al tiempo que se mantiene un crecimiento normal (AU)

Objectives: The main objective of this study was to evaluate the tolerance of a new casein hydrolyzate formula, and its efficacy during a 3 months consumption period by infants with IgE-mediated cow’s milk protein allergy (CMPA). Methods: This study was part of randomized, double blind study performed in 15 Spanish hospitals. In the present paper the results of the arm that received an extensively hydrolyzed casein formula are reported. Full term infants aged up to 9 months were included to check that 97% of them tolerate the formula at introduction. The CMPA was confirmed by a specific IgE dosage before inclusion. An oral food challenge was made with the formula. Over 3 months, the evolution of the clinical symptoms and the growth were evaluated. Results: The 25 boys and 22 girls included tolerated the formula at introduction without any adverse reaction during the first day of formula intake, meaning that 97% of the infants tolerated the treatment at introduction (p= 0.0112). Three adverse events were reported 4, 6 and 10 days later and were considered possibly or probably related to the study formula indicating an effective delayed tolerance of more than 93% of infants. At 1 month of follow-up, the condition of the infants was greatly improved as indicated by the dramatic decrease of the digestive symptoms from 40.4% to 13%, and the total regression of all the other symptoms. The growth of the infants over 3 months showed a normal pattern, in agreement with the World Health Organization (WHO) growth references. Conclusion: This new casein hydrolyzate formula shows a rate of tolerance >97%, it is efficient to rapidly improve clinical symptoms and allows a normal growth pattern in infants with CMPA (AU)

The predictive value of specific immunoglobulin E levels in serum for the outcome of the development of tolerance in cow's milk allergy.

BACKGROUND: Immunoglobulin E-mediated allergy to cow's milk protein (CMP) tends to subside over years of follow-up. The gold standard for detecting such allergy has been the oral challenge test. The development of some other test for determining the correct timing of the oral challenge test would avoid unnecessary patient discomfort. The aim of this study was to determine whether monitoring cow's milk (CM) specific IgE levels over time can be used as a predictor for determining when patients develop clinical tolerance. METHODS: A prospective 4-year follow-up study was made of 170 patients with IgE-mediated allergy to CMP, involving periodic evaluations (12, 18, 24, 36 and 48 months) with the determination of casein and CM specific IgE on each visit, along with CM challenge testing. ROC curves were used to analyse the sensitivity, specificity and predictive values of the casein and CM specific IgE levels versus the challenge test outcomes at the different moments of follow-up. RESULTS: In the course of follow-up, 140 infants (82 %) became tolerant. Specific IgE levels to CM: 2.58, 2.5, 2.7, 2.26, 5 kU(A)/l and to casein: 0.97, 1.22, 3, 2.39, 2.73 kU(A)/l, respectively, predicted clinical reactivity (greatest diagnostic efficiency values) at the different analysed moments of follow-up (12, 18, 24, 36 and 48 months). CONCLUSIONS: Quantification of CMP specific IgE is a useful test for diagnosing symptomatic allergy to CM in the paediatric population, and could eliminate the need to perform oral challenges tests in a significant number of children.

Clinical and immunological profile of children aged 5-9 years with persistent egg allergy before oral immunotherapy with egg. A multicenter, randomized controlled trial of the Spanish Society of Pediatric Allergy, Asthma and Clinical Immunology (SEICAP)

BACKGROUND: In children with egg protein allergy (EA), the probability of overcoming the allergy decreases with age, and the possibility of suffering severe adverse reactions as a consequence of dietetic transgressions results in worsened quality of life. One treatment option in such cases is oral immunotherapy (OIT) with foods. METHODS: We present a cohort of children with EA scheduled for OIT with pasteurized raw egg white, describing their clinical and allergic characteristics before the start of OIT. RESULTS: The median age was six years, and 93% of the patients also suffered other allergies (58% asthma and 38.6% allergy to more than two food groups). In the last year, 14.8% had suffered a severe reaction due to dietetic transgression with egg. The median IgE specific of egg white titer was 38.5 kU/l. A double-blind placebo-controlled food challenge with cooked egg white was performed, and if the test proved positive, it was repeated with pasteurized raw egg white. The mean symptoms-provoking dose was 1.26 g and 0.55 g for cooked egg white and raw egg white, respectively. An IgE specific of ovomucoid titer of <2.045 kU/l differentiated those patients that tolerated cooked egg white. CONCLUSIONS: OIT with egg is regarded as an option in patients with persistent egg allergy. In the previous challenge test, an IgE specific of ovomucoid titer of <2.045 kU/l differentiates those patients that tolerate cooked egg white

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Atopic dermatitis today.

This review focuses on recent literature regarding atopic dermatitis (AD). New insights in epidemiology, diagnostic criteria, quality of life measures, provocative factors, patophysiology and therapy will be highlighted. New diagnostic criteria for AD set by the UK working party allow easier epidemiologic studies to cope with this increasingly prevalent disease. Immunomodulating therapy with cyclosporine holds promise in the treatment of refractory AD.

[Treatment of acute crises of bronchial asthma in children using subcutaneous salbutamol as an alternative to adrenaline: comparative study]. / Tratamiento de las crisis agudas de asma bronquial en niños con salbutamol subcutáneo como alternativa a la adrenalina: estudio comparativo.

A prospective study has been made in order to asses the efficacy of subcutaneous salbutamol as acute treatment for asthmatic crisis, comparing the results with those of adrenaline. The series consisted of 30 cases, divided into two groups according to the administered treatment, with ages ranging between 5 to 18 years. Once the clinical examination and spirometric measurements were made the first group was treated with subcutaneous adrenaline 0.1 cc/kg (max.; 0.5 cc), while the second was treated with subcutaneous salbutamol 20 micrograms/kg (max.: 500 micrograms). A clinical and spirometric examination was performed at 15, 30, 60 and 90 minutes. A similar increase in FEV1 was observed in the two groups at 15 minutes, maintaining this increase for 90 minutes in the group treated with salbutamol and decreasing in the group treated with adrenaline, being the difference statistically significant (p less than 0.001). In view of this results it seems advisable to administer subcutaneous salbutamol as urgent treatment for an acute asthmatic crisis.

A prospective and multicenter safety-monitoring study of a short up-dosing schedule of immunotherapy with a mass-units-standardized extract of mites.

A prospective, multicenter pharmacovigilance study was carried out to evaluate the safety of a new 7-dose treatment schedule of subcutaneous immunotherapy as opposed to the conventional 13 doses normally recommended. The study was carried out in 14 centers and included 261 patients (children and adults) with respiratory allergic disease due to sensitization to mites (Dermatophagoides pteronyssinus and/or farinae). A total of 2290 doses were administered under the direct supervision of the participating specialists. One hundred and ten reactions in 63 patients (24.1%) were recorded, representing 4.8% of the total doses administered. Most of the reactions (98) were local. Only 12 were systemic (0.5% of the administered doses) and occurred in 10 patients (3.8% of the sample). Ten reactions reverted quickly with rescue medication. The maintenance dose had to be lowered in one patient and another patient was withdrawn from the study after suffering two asthmatic crises after two consecutive doses. In view of the results obtained, we can conclude that the new schedule shows an acceptable tolerance profile and does not present a greater risk of reactions than the conventional scheme of 13 doses using an identical extract. Moreover, the new schedule represents substantial savings in the number of doses and visits required to reach the maintenance dose.

Position document: IgE-mediated allergy to egg protein

Egg is the food that most often causes allergy in young Spanish children, with an incidence of 2.4–2.6% in the first 2 years of life. The prevalence of sensitisation and allergy to egg is greater in children with allergy to cow's milk and in those suffering atopic dermatitis. The protein component from egg white is the cause of the allergic response in child. The major allergens in egg white are ovomucoid and ovalbumin. Most of the allergic reactions affect the skin, followed by gastrointestinal and respiratory systems. Egg allergy is one of the most common causes of severe anaphylaxis. The diagnosis of egg allergy is based on the existence of a suggestive clinical history, a positive allergy study and the subsequent application of controlled exposure testing, which represents the gold standard for confirming the diagnosis. The treatment of egg allergy is based on the avoidance of egg protein intake. A subgroup of egg-allergic patients are tolerant to cooked egg. In these cases, only uncooked egg must necessarily be avoided. Maintaining a diet with strict egg avoidance is difficult, and transgressions are relatively common. The patient, family, and school environment should receive education and training in the avoidance of egg and in the management of possible allergic reactions. With an avoidance diet, up to 15–20% of children will remain allergic and the severity of the reactions will increase over the years. In these more severe cases of egg-allergy, it becomes more difficult to adhere to the avoidance diet over the years, with a significant decrease in patient quality of life. Oral tolerance induction can be regarded as a therapeutic option for IgE-mediated egg allergy. The anti-IgE, omalizumab, might become another genuine therapeutic option for food allergy, not only to prevent allergic reactions after a contact with egg, but also as a complementary treatment to oral tolerance induction for egg allergy, with the purpose of reducing adverse reactions (AU)

The administration of influenza vaccine to children with egg allergy is safe in children that do not manifest severe reactions after egg intake, and in children who tolerate cooked egg. The triple viral vaccine (MMR) can be given to egg-allergic children in their usual vaccination centre, with no added risk. Different medicinal products can be formulated with egg proteins, and therefore should be avoided in children with egg allergy (AU)

Changes in IL-10 and specific antibodies associated to successful Dermatophagoides pteronyssinus immunotherapy in children during the first year of treatment

Background: Allergen-specific immunotherapy (SIT) is a long-term treatment of respiratory allergy. Objective: To look for early predictors of the effectiveness of Dermatophagoides pteronyssinus SIT. Methods: A prospective multi-centre study was carried out in Spain. Children with D. pteronyssinus rhinitis or asthma were invited to participate. The study was divided into times: T0 (recruitment); T1 (inclusion); T2 a-f (immunotherapy times) and T3 (the end of study). Efficacy of SIT was assessed by clinical scores, visual analogue scales (VAS) and lung function tests. We performed D. pteronyssinus skin tests at T1 and T3, and determined specific serum IgE, IgG4 and IL-10 at T1, T2f and T3.Data were analysed using Mann–Whitney and Kruskal–Wallis tests, compared using Wilcoxon and Chi-square tests, and correlated to Spearman test. All tests had a significance level of 0.05. Results: Thirty-eight children completed the study. At T1 all had rhinitis and 34 also had asthma. At T3, 30 patients had improved, six experienced no changes and two worsened. Improvement was associated to FEV1/FVC and VAS improvement; to a reduction in D. pteronyssinus skin prick test; to a progressive increase in serum levels of D. pteronyssinus IgE, and D. pteronyssinus, Der p1 and Der p2 IgG4. IL-10 levels showed an early increase at T2f (the end of initial build-up immunotherapy phase), and then a reduction at T3 (the end of a year of immunotherapy).Improvement associated to an early increase in IL-10 and was correlated with VAS and specific IgG4 evolution(AU)

The predictive value of specific immunoglobulin E levels in serum for the outcome of the development of tolerance in cow’s milk allergy

Background: Immunoglobulin E-mediated allergy to cow’s milk protein (CMP) tends to subside over years of follow-up. The gold standard for detecting such allergy has been the oral challenge test. The development of some other test for determining the correct timing of the oral challenge test would avoid unnecessary patient discomfort. The aim of this study was to determine whether monitoring cow’s milk (CM) specific IgE levels overtime can be used as a predictor for determining when patients develop clinical tolerance. Methods: A prospective 4-year follow-up study was made of 170 patients with IgE-mediated allergy to CMP, involving periodic evaluations (12, 18, 24, 36 and 48 months) with the determination of casein and CM specific IgE on each visit, along with CM challenge testing. ROC curves were used to analyse the sensitivity, specificity and predictive values of the casein and CM specific IgE levels versus the challenge test out comes at the different moments of follow-up. Results: In the course of follow-up, 140 infants (82 %) became tolerant. Specific IgE levels to CM:2.58, 2.5, 2.7, 2.26, 5 kUA/l and to casein: 0.97, 1.22,3, 2.39, 2.73 kUA/l, respectively, predicted clinical reactivity (greatest diagnostic efficiency values) at the different analysed moments of follow-up (12, 18, 24,36 and 48 months). Conclusions: Quantification of CMP specific IgE is a useful test for diagnosing symptomatic allergy toCM in the paediatric population, and could eliminate the need to perform oral challenges tests in a significant number of children

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Anafilaxia en el curso de una inseminación intrauterina / Anaphylaxis in the course of intrauterine insemination

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