Asymptomatic LTP sensitisation is common in plant-food allergic children from the Northeast of Spain.

BACKGROUND: The sensitisation profile at molecular level in plant-food allergy is complex. Several allergens may be involved, with different potential for severe reactions. lipid transfer proteins (LTP) are considered the most relevant plant-food allergens in adults in Mediterranean countries, but less is known in children. AIM: To describe the clinical pattern and sensitisation profile of children with plant-food allergy and LTP sensitisation from Northeast Spain. METHODS: Children with history of immediate reaction to plant-food(s), positive skin-prick-test to the culprit plant-food(s) and specific-IgE to plant-food LTPs were analysed. RESULTS: 130 children were included. 69.2% (90/130) had reacted to ≥2 taxonomically unrelated plant-foods. Peach, walnut, hazelnut and peanut were most frequently involved. Reactions severity ranged from anaphylaxis (45.4%, 59/130) to oral symptoms only. Sensitisation to a particular plant-food LTP not always caused clinical symptoms with that plant-food; 69% (40/58) and 63% (17/27) of peach- and walnut-tolerant subjects had positive rPru p 3 and nJug r 3 specific IgE, respectively. 65.4% (85/130) of children were also sensitised to storage proteins, which was associated to anaphylaxis and nut allergy. However, 60% of patients without nuts/seeds allergy were sensitised to storage proteins. Specific-IgE levels to LTPs and/or storage proteins were not useful to predict allergy (vs. tolerance) to peach, walnut, peanut or hazelnut. CONCLUSIONS: Sensitisation to LTP and/or storage proteins without clear clinical significance is relatively common. Prospective longitudinal studies are required to evaluate the relevance of these silent sensitisations over time. Caution is required when interpreting the results of molecular-based diagnostic tools in clinical practice.

Tolerability during double-blind randomized phase I trials with the house dust mite allergy immunotherapy tablet in adults and children.

BACKGROUND AND OBJECTIVE: The orodispersible house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet (ALK, Denmark) is being developed for the treatment of HDM respiratory allergic disease. The objective of the 2 phase I trials was to investigate tolerability and the acceptable dose range of HDM SLIT-tablet treatment in adults and children with HDM respiratory allergic disease. PATIENTS AND METHODS: The trials were randomized, multiple-dose, dose-escalation, double-blind, placebo-controlled phase I trials including patients with HDM-induced asthma, with or without rhinoconjunctivitis. Both trials were registered in EudraCT (Trial 1: 2005-002151-41; Trial 2: 2007-000402-67). Trial 1 included 71 adults (18-63 years) and trial 2 included 72 children (5-14 years). Both trials included 6 dose groups that were randomized 3:1 to active treatment or placebo once daily for 28 days. Adverse events (AEs) were coded in MedDRA (version 8.1 or later). Immunological variables included specific IgE and IgE-blocking factor. RESULTS: No serious AEs were reported. In trial 1 (maximum dose, 32 development units [DU]), 1 patient in the 16 DU group discontinued due to AEs. The entire 32 DU group was discontinued as 1 patient had a severe adverse reaction. In trial 2 (maximum dose, 12 DU), no patients discontinued prematurely. The most frequently reported AEs were mild application-site related events. The total number of events was dose-related within each trial. HDM SLIT-tablet treatment induced changes in immunological parameters in a dose-dependent manner. CONCLUSIONS: These trials demonstrate that doses up to 12 DU of HDM SLIT-tablet were tolerated in the selected populations, and thus are suitable for further clinical investigations in adults and children with HDM respiratory allergic disease.

Prevalence and clinical profile of difficult-to-control severe asthma in children: results from pneumology and allergy hospital units in Spain.

BACKGROUND: Severe asthma is often poorly controlled and its prevalence in Spanish children is unknown. The aim was to determine the prevalence of difficult-to-control severe asthma in children, the agreement of asthma control between physicians and Spanish Guidelines for Asthma Management (GEMA), and the health-related quality of life (HRQoL) for children and parents. METHODS: Observational, cross-sectional, two-phase, multicentre study. In the first phase, all children who attended pneumology and allergy units during a three-month period were classified according to physicians' criteria as patients with: asthma, severe asthma, or difficult-to-control severe asthma. Patients aged 6-14 years with severe asthma (difficult-to-control or controlled) were included in the second phase. RESULTS: 12,376 asthmatic children were screened in the first phase. According to physicians' criteria, 8.8% (95% CI 8.3-9.3%) had severe asthma. Of these, 24.2% (95% CI, 21.7-26.8%) had difficult-to-control severe asthma. 207 patients with severe asthma (mean age 10.8 ± 2.3 years; 61.4% male; mean of 5.5 ± 3.4 years since asthma diagnosis) were included in the second phase. Compared to the patients with controlled asthma, children with difficult-to-control asthma had a higher number of exacerbations, emergency room or unscheduled primary care visits in the previous year (p<0.0001, all) and poor HRQoL (p<0.0001, both children and caregivers). 33.3% of patients with controlled asthma according to physicians' criteria were poorly controlled according to GEMA. CONCLUSIONS: Around one in four asthmatic children with severe disease had difficult-to-control asthma, although one third was underestimated by physicians. Children with difficult-to-control severe asthma had a poor HRQoL that also affected their parents.

Safety and predictors of adverse events during oral immunotherapy for milk allergy: severity of reaction at oral challenge, specific IgE and prick test.

BACKGROUND: Strict avoidance is the only accepted management for cow's milk (CM) allergy. CM oral immunotherapy (CM-OIT) is under investigation. OBJECTIVES: To evaluate long-term safety of CM-OIT. To identify clinical/immunological predictors of adverse events. METHODS: Prospective longitudinal epidemiological intervention study. CM-allergic children aged 5-18 underwent a Spanish-approved CM-OIT protocol without premedication. Clinical data, skin prick test (SPT) and specific IgE (sIgE) at baseline and 1 year after OIT were registered. All dose-related reactions, treatments needed and cofactors involved were recorded. Through survival analysis, we studied the cumulative probability of reactions resolution over time and clinical/immunological risk factors of reactions persistence. RESULTS: 81 children were recruited. Mean follow-up was 25 months. 95% of children suffered reactions, 91% of which affected a single organ. Reactions were heterogeneously distributed: (a) 60 children (75%) had occasional symptoms which ceased over time. 86% of them reached complete desensitization (200 mL). (b) 20 children (25%) suffered frequent (78% of total reactions), more severe and unpredictable reactions, which persisted during follow-up or led to withdrawal (6 cases). Reactions persistence was associated with a higher frequency and severity. Kaplan-Meier estimate revealed a cumulative probability of reactions resolution of 25% at 3 months (95% CI: 1.9-4.1) and 50% (95% CI: 6.1-9.9) at 8 months based on all patients. Cox proportional hazards multivariate regression model identified 3 variables (CM-sIgE ≥ 50 KU L(-1) , CM-SPT ≥ 9 mm and Sampson's severity grades 2, 3 and 4 at baseline food challenge) as independent risk factors of reactions persistence. The combination of 2 or 3 of these factors involved hazard ratios to develop persistent reactions of 2.26 (95% CI: 1.14-4.46; P = 0.019) and 6.06 (95% CI: 2.7-13.7; P < 0.001), respectively. CLINICAL IMPLICATIONS: CM-OIT was insufficiently safe in 25% of children. The above-mentioned clinical and immunological parameters would help clinicians to identify highly reactive patients before CM-OIT. In them, individualized schedules and premedication should be considered.

Allergy to quail's egg without allergy to chicken's egg. case report.

INTRODUCTION: We present a case of quail's egg allergy without allergy to chicken's egg. CASE: Girl of 10.5 years old who presents anaphylactic reaction after she ate an uncooked quail's egg. She had eaten boiled quail's egg before. She eats chicken's eggs without clinical symptoms. METHODS: We made a prick to chicken's egg and prick-by-prick to uncooked quail's and raw chicken's egg. We determined specific IgE to chicken's egg; electrophoresis and IgE by immunoblot to eggs from chicken, duck, goose, and quail. RESULTS: We obtained negative results to prick, prick-by-prick and specific IgE to chicken's egg. Prick-by-prick to quail's egg was positive. By immunoblot we recognised a protein in quail's egg white, which is ovotransferrin without any similar bands in other species' eggs. CONCLUSIONS: The protein that we recognised is a specific protein of quail's egg. These proteins did not cross-react with proteins of chicken's egg. Cooking may degrade such proteins.

Eosinophilic oesophagitis: clinical manifestations and treatment options. The role of the allergologist.

Eosinophilic oesophagitis (EO) is an infrequent disorder that is currently underdiagnosed. It has been described in both adults and in children, and is more prevalent among males. The etiology of EO is not clear, though atopy has been suggested as playing an important role in the development of the disease. The clinical presentation of EO is varied, and a differential diagnosis with other digestive tract disorders is required particularly gastro-oesophageal re-flux. Dysphagia and food bolus impactation within the oesophagus are the most characteristic symptoms. Diagnostic confirmation is obtained from multiple oesophageal biopsy, with the detection in some sample or samples of over 15 eosinophils per high-magnification microscopic field. An allergological study is needed to evaluate the existence of allergens (perennial or seasonal environmental allergens and food allergens) responsible for the eosinophilic infiltration found at oesophageal level. There is no specific treatment for EO, and topical corticosteroids (swallowed) are currently the pharmacological treatment of choice. Dietary therapy in children with food allergy as the causal factor may prove effective, though the existence of polysensitisation complicates the correct implementation of such treatment. Oesophageal dilatation is reserved for cases with severe dysphagia, and is not without complications. Treatment with anti-IL-5, antileukotrienes, azathioprine, 6-mercaptopurine, anti-IgE, etc., could constitute alternatives to topical corticosteroids, although information is still lacking on their long-term safety and efficacy in the paediatric population.

Risk factors of developing asthma in children with recurrent wheezing in the first three years of life.

INTRODUCTION: recurrent wheezing is a common problem during the first years of life, but it is still difficult to identify which of these children may develop asthma in the future. OBJECTIVES: To study risk factors of developing asthma in a group of patients with frequent wheezing during the first three years of life. MATERIAL AND METHODS: A prospective study was performed of a group of 60 patients, aged below three, referred to our Hospital for recurrent wheezing. Age, sex, parental and personal history of atopy, clinical features, laboratory tests, evolution and response to treatment were analyzed. RESULTS: 60 patients were enrolled in study. Most of children were boys and have had the first episode of wheezing after the 6 months of life. 63 % had personal history of atopy and 55 % parental history of allergy. The group of atopic children had more wheezing exacerbations and worse evolution than the group of non atopic. They also had more treatment necessities. CONCLUSIONS: The identification of young children at high risk of developing asthma could permit an early intervention before irreversible changes in the airway appeared.

Recommendations for administering the triple viral vaccine and antiinfluenza vaccine in patients with egg allergy.

Actually, food allergy is an emerging pathology; and egg allergy is the most frequent in childhood. The recommendations for measles, mumps and rubella (MMR) and influenza vaccination are increasing each year. This implementation increases the exposure of patients with egg allergy to such vaccines. In Spain, since 2004 the only available vaccine for MMR is grown in cultures of fibroblast from chick embryos; previously, patients with egg allergy were vaccinated with an alternative vaccine cultivated in diploid human cells which is no longer commercialized. Influenza vaccines grow in chick egg and the final product contains egg proteins (large variation in egg protein content has been reported). As controversy exist, the Food Allergy Committee of Spanish Society of Clinical Immunology and Pediatric Allergy decided to report some recommendations for the safe administration of MMR and influenza vaccines in patients with egg allergy. In summary, MMR vaccine is safe for children with egg allergy, only in patients with severe anaphylactic reaction after egg ingestion is recommended the administration in his reference hospital. Influenza vaccine is contraindicated in patients with severe anaphylactic reaction after egg ingestion. The rest can receive influenza vaccine in a 2-dose protocol with a vaccine that contains no more than 1.2 mcg of egg protein for mL.

Recommendations for administering the triple viral vaccine and antiinfluenza vaccine in patients with egg allergy / Recomendaciones para la administración de la vacuna triple vírica y la vacuna anti-influenza en pacientes con alergia al huevo

Actually, food allergy is an emerging pathology; and egg allergy is the most frequent in childhood. The recommendations for measles, mumps and rubella (MMR) and influenza vaccination are increasing each year. This implementation increases the exposure of patients with egg allergy to such vaccines. In Spain, since 2004 the only available vaccine for MMR is grown in cultures of fibroblast from chick embryos; previously, patients with egg allergy were vaccinated with an alternative vaccine cultivated in diploid human cells which is no longer commercialized. Influenza vaccines grow in chick egg and the final product contains egg proteins (large variation in egg protein content has been reported). As controversy exist, the Food Allergy Committee of Spanish Society of Clinical Immunology and Pediatric Allergy decided to report some recommendations for the safe administration of MMR and influenza vaccines in patients with egg allergy. In summary, MMR vaccine is safe for children with egg allergy, only in patients with severe anaphylactic reaction after egg ingestion is recommended the administration in his reference hospital. Influenza vaccine is contraindicated in patients with severe anaphylactic reaction after egg ingestion. The rest can receive influenza vaccine in a 2-dose protocol with a vaccine that contains no more than 1.2 mcg of egg protein for mL

En la actualidad, la alergia alimentaria constituye una patología emergente; siendo la alergia al huevo la más frecuente en la infancia. Las recomendaciones para la vacunación de sarampión, parotiditis y rubéola (vacuna triple vírica), así como para la vacuna antigripal, aumentan cada año. El cumplimiento de estas recomendaciones aumenta la exposición de pacientes alérgicos al huevo a dichas vacunas. En España, desde el año 2004 solo se dispone de vacuna triple vírica cultivada en fibroblastos de embrión de pollo; anteriormente, los pacientes alérgicos al huevo se inmunizaban con una vacuna alternativa cultivada en células diploides humanas que no se comercializa actualmente. La vacuna antigripal se cultiva en huevos de gallina y el producto final contiene proteína de huevo (la cantidad en proteína de huevo es muy variable). Dada la existente controversia, el Comité de Alergia Alimentaria de la Sociedad Española de Inmunología Clínica y Alergia Pediátrica ha decidido establecer una serie de recomendaciones para la administración segura de la vacuna triple vírica y la vacuna antigripal en pacientes alérgicos al huevo. En resumen, la vacuna triple vírica es segura para los niños alérgicos al huevo, sólo en los pacientes con reacción anafiláctica grave tras la ingesta de huevo se recomienda su administración en su hospital de referencia. La vacuna antigripal está contraindicada en pacientes con reacción anafiláctica grave tras la ingesta de huevo. El resto pueden vacunarse con una administración fraccionada en 2 dosis y con una vacuna que contenga igual o menos de 1.2 mcg de proteína de huevo por ml

Polysensitization to aeroallergens and food in eosinophilic esophagitis in a pediatric population.

There are few studies on eosinophilic esophagitis (EE) in the pediatric population in Europe. We present our data and emphasize the following findings: a) all patients had symptoms of allergic respiratory disease prior to receiving a diagnosis of EE with polysensitization (aeroallergens, food allergens); and b) in contrast with the results of earlier studies, food sensitization in our series most often corresponded to legumes.

Shock y sintomatología digestiva en un neonato: una forma grave de presentación de la alergia a proteínas de leche de vaca / Shock and digestive symptoms in a neonate: a severe presentation of allergy to cow’s milk proteins

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Variability of immunodeficiency associated with ataxia telangiectasia and clinical evolution in 12 affected patients.

Ataxia telangiectasia (AT) is an infrequent condition, which is difficult to diagnose in children. The objective was to describe the evolution of all affected patients controlled in our hospital and to highlight the keys for an early diagnosis considering the variability of immunological disorders. The present study is a retrospective review of all patients diagnosed and controlled of AT in our hospital. Twelve patients were found, including two couples of siblings. The most frequent reason for consultation was unstable gait. Seven patients suffered repeated infections, being pneumonia the most frequent cause of infection, followed by sinusitis. One of the patients developed Burkitt's lymphoma, and another patient, Hodgkin's lymphoma, which caused the death of the patient at the age of 11. A couple of siblings aged 17 and 22 years developed insulin-resistant diabetes mellitus. The most frequent immunity disorders were the IgG deficiency and the decrease of T lymphocytes. Seven patients were treated with non-specific gamma-globulin. By the end of the follow-up, 8 patients (ages ranged 7 to 12 years) lost gait. Molecular genetic testing was conducted in patients who are still cared for in our hospital. Clinical suspicion of this entity will lead to an early diagnosis, the treatment of complications, and to provide genetic counselling for the families.

Challenge testing in children with allergy to cow's milk proteins.

OBJECTIVES: To evaluate clinical response after challenge testing in infants with allergy to cow's milk proteins at diagnosis and again when these infants were aged 1 year old and had been fed an exclusion diet. MATERIAL AND METHODS: We performed a prospective study of 49 infants aged less than 6 months with a clinical history suggestive of cow's milk protein allergy, positive skin prick test and specific IgE for alpha-lactalbumin, beta-lactoglobulin and casein. In all children challenge test with cow-milk adapted formula was carried out at diagnosis. The same procedures were repeated when the children were aged 1 year but challenge testing was repeated only in children with a negative skin prick test and specific IgE antibodies to cow's milk proteins. RESULTS: At diagnosis, challenge tests produced immediate hypersensitivity reactions in 94% of infants. Late reactivity (i.e., more than 2 hours after challenge) was found in only 6% of infants, all of whom presented dyspepsia. When the infants were aged 1 year, and after results of immunological study were negative, a further challenge test was performed in 24 (49%) of lactating infants included in the study. Of these 24 infants, positive challenge was found in 5 (21%). None of the infants presented immediate symptomatology (clinical features appeared 7 days after the reintroduction of cow's milk proteins). CONCLUSIONS: Ninety-four percent of challenge tests performed at diagnosis provoked immediate reactions. The results of challenge tests after a negative skin prick test in children with normal concentrations of specific IgE were positive in 21% infants, who presented late reactivity (a mean of 7 days after milk ingestion).