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

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Humoral deficiency in three paediatric patients with genetic diseases

BACKGROUND: Primary immunodeficiencies (PID) represent a heterogeneous group of genetic disorders characterised by poor or absent function in one or more components of the immune system. Humoral or antibody immunodeficiencies are the most common form of PID, of which common variable immunodeficiency (CVID) is the most frequent symptomatic form. CVID is usually characterised by hypogammaglobulinaemia with poor antibody specificity, and an increased susceptibility to infections, autoimmunity and lymphoproliferation. Fewer than 10% of CVID patients have a known monogenic basis. Several chromosomal abnormalities (chromosome 18q-syndrome, monosomy 22, trisomy 8 and trisomy 21) are currently identified as causes of hypogammaglobulinaemia, and can manifest with recurrent infections and mimic CVID. Methods; Review of clinical charts and laboratory results of paediatric patients followed in the outpatient clinic of PID with a diagnosis of genetic disease and humoral immunodeficiency. RESULTS: Three patients with different genetic diseases (19p13.3 deletion, a ring 18 chromosome and Kabuki syndrome), were identified. During follow-up, they developed signs and symptoms suggestive of humoral deficiency mimicking CVID, despite which immunoglobulin levels were quantified with considerable delay with respect to symptoms onset, and specific management was subsequently delayed. CONCLUSIONS: Patients with genetic abnormalities and recurrent infections should be evaluated for hypogammaglobulinaemia. An early diagnosis of humoral deficiency can allow treatment optimisation to prevent complications and sequelae

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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.

Humoral deficiency in three paediatric patients with genetic diseases.

BACKGROUND: Primary immunodeficiencies (PID) represent a heterogeneous group of genetic disorders characterised by poor or absent function in one or more components of the immune system. Humoral or antibody immunodeficiencies are the most common form of PID, of which common variable immunodeficiency (CVID) is the most frequent symptomatic form. CVID is usually characterised by hypogammaglobulinaemia with poor antibody specificity, and an increased susceptibility to infections, autoimmunity and lymphoproliferation. Fewer than 10% of CVID patients have a known monogenic basis. Several chromosomal abnormalities (chromosome 18q-syndrome, monosomy 22, trisomy 8 and trisomy 21) are currently identified as causes of hypogammaglobulinaemia, and can manifest with recurrent infections and mimic CVID. METHODS: Review of clinical charts and laboratory results of paediatric patients followed in the outpatient clinic of PID with a diagnosis of genetic disease and humoral immunodeficiency. RESULTS: Three patients with different genetic diseases (19p13.3 deletion, a ring 18 chromosome and Kabuki syndrome), were identified. During follow-up, they developed signs and symptoms suggestive of humoral deficiency mimicking CVID, despite which immunoglobulin levels were quantified with considerable delay with respect to symptoms onset, and specific management was subsequently delayed. CONCLUSIONS: Patients with genetic abnormalities and recurrent infections should be evaluated for hypogammaglobulinaemia. An early diagnosis of humoral deficiency can allow treatment optimisation to prevent complications and sequelae.

Position document: IgE-mediated cow's milk allergy

The present document offers an update on the recommendations for managing patients with cow's milk allergy - a disorder that manifests in the first year of life, with an estimated prevalence of 1.6-3% in this paediatric age group. The main causal allergens are the caseins and proteins in lactoserum (beta-lactoglobulin, alpha-lactoalbumin), and the clinical manifestations are highly variable in terms of their presentation and severity. Most allergic reactions affect the skin, followed by the gastrointestinal and respiratory systems, and severe anaphylaxis may occur. The diagnosis of cow's milk allergy is based on the existence of a suggestive clinical history, a positive allergy study and the subsequent application of controlled exposure testing, which constitutes the gold standard for confirming the diagnosis. The most efficient treatment for cow's milk allergy is an elimination diet and the use of adequate substitution formulas. The elimination diet must include milk from other mammals (e.g., sheep, goat, etc.) due to the risk of cross-reactivity with the proteins of cow's milk. Most infants with IgE-mediated cow's milk allergy become tolerant in the first few years of life. In those cases where cow's milk allergy persists, novel treatment options may include oral immunotherapy, although most authors do not currently recommend this technique in routine clinical practice. Enough evidence is not there to confirm the efficacy of elimination diets in the mother and infant for preventing the appearance of cow's milk allergy. Likewise, no benefits have been observed with prebiotic and probiotic dietetic supplements in infants for preventing food allergy

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Position document: IgE-mediated cow's milk allergy.

The present document offers an update on the recommendations for managing patients with cow's milk allergy - a disorder that manifests in the first year of life, with an estimated prevalence of 1.6-3% in this paediatric age group. The main causal allergens are the caseins and proteins in lactoserum (beta-lactoglobulin, alpha-lactoalbumin), and the clinical manifestations are highly variable in terms of their presentation and severity. Most allergic reactions affect the skin, followed by the gastrointestinal and respiratory systems, and severe anaphylaxis may occur. The diagnosis of cow's milk allergy is based on the existence of a suggestive clinical history, a positive allergy study and the subsequent application of controlled exposure testing, which constitutes the gold standard for confirming the diagnosis. The most efficient treatment for cow's milk allergy is an elimination diet and the use of adequate substitution formulas. The elimination diet must include milk from other mammals (e.g., sheep, goat, etc.) due to the risk of cross-reactivity with the proteins of cow's milk. Most infants with IgE-mediated cow's milk allergy become tolerant in the first few years of life. In those cases where cow's milk allergy persists, novel treatment options may include oral immunotherapy, although most authors do not currently recommend this technique in routine clinical practice. Enough evidence is not there to confirm the efficacy of elimination diets in the mother and infant for preventing the appearance of cow's milk allergy. Likewise, no benefits have been observed with prebiotic and probiotic dietetic supplements in infants for preventing food allergy.

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.

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

Recomendaciones para la administración de la vacuna antigripal en pacientes alérgicos al huevo / Recommendations for administration of the influenza vaccine

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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.

Polysensitization to aeroallergens and food in eosinophilic esophagitis in a pediatric population / Polisensibilización a aeroalergenos y alimentos en la esofagitis eosinofílica en una población pediátrica

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

Hay pocos estudios sobre esofagitis eosinofílica (EE) en la población pediátrica en Europa. Presentamos nuestros datos, destacando los siguientes hallazgos: a) presencia de enfermedad alérgica respiratoria en todos los pacientes previamente diagnosticados de EE, polisensibiizados (aeroalergenos, alimentos); b) sensibilización a alimentos en nuestra serie, la mayoría a legumbres, en contraste con el resultado de estudios anteriores

Seguridad de la vacunación triple vírica en pacientes con alergia al huevo / Safety of MMR immunization in egg-allergic children

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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.

[Anemia in primary care: etiology and morphological characteristics]. / Anemias en atención primaria: etiología y características morfológicas.

OBJECTIVE: To find the morphological characteristics and causes of the types of anaemia seen at a primary care centre. DESIGN: Descriptive, observational study. SETTING: Urban health centre. PATIENTS: People attending for a year who had an anaemia defined by haemoglobin figures below 13 g/dl in males and 12 g/dl in women. MEASUREMENTS AND MAIN RESULTS: 152 patients with anaemia were identified. The most common types of anaemia were iron-deficiency anaemia (IDA), anaemia due to chronic illness (ACI) and post-haemorrhage anaemia (48%, 26.3% and 6.6%, respectively). Anaemia due to vitamin B12 deficit was detected in four patients, Thalassaemia minor in two, haemolytic anaemia in two, and a refractory anaemia in one patient. The most common cause of IDA was gynaecological in origin; and the commonest cause of ACI was neoplasm. The main findings of digestive origin in IDA were oesophagitis in two patients, duodenal ulcer in one, erosive gastritis in one, gastric neoplasm in one, colonic neoplasm in two and Crohn's disease in one. 13.7% of the anaemia studied in PC required hospital referral. CONCLUSIONS: Anaemia is a common health problem in primary care (PC), with a rough incidence of one case per month per doctor. Its main types are iron-deficiency anaemia and anaemia due to chronic illness. Most cases were detected in PC and most can be studied properly at this care level.

Anemias en atención primaria: etiología y características morfológicas / Anaemia in primary care: aetiology and morphological characteristics

Objetivo. Conocer las características morfológicas y causales de las anemias que se presentan en un centro de asistencia primaria (CAP). Diseño. Estudio observacional, descriptivo. Emplazamiento. Centro de salud urbano. Pacientes. Personas atendidas durante un año que presentaban una anemia definida por cifras de hemoglobina inferiores a 13 g/dl en el varón y 12 en la mujer. Mediciones y resultados principales. Se identificaron 152 pacientes con anemia. Los tipos de anemia más frecuentes fueron anemia ferropénica (AF), anemia por enfermedad crónica (AEC) y anemia posthemorrágica (48, 26,3 y 6,6 por ciento, respectivamente). Se detectó anemia por déficit de vitamina B12 en 4 pacientes, talasemia menor en 2, anemia hemolítica en 2 y anemia refractaria en un paciente. El origen ginecológico fue la causa más habitual de AF y las neoplasias de AEC. Los principales hallazgos en las AF de origen digestivo fueron esofagitis en 2 pacientes, ulcus duodenal en uno, gastritis erosiva en uno, neoplasia gástrica en uno, neoplasia de colon en 2 y enfermedad de Crohn en uno. Un 13,7 por ciento de las anemias estudiadas en AP precisaron derivación hospitalaria. Conclusiones. La anemia es un problema de salud frecuente en atención primaria (AP), con una incidencia aproximada de un caso al mes por médico. Sus principales causas son la AF y la AEC. La mayor parte de los casos se detectan en AP y la mayoría de ellos pueden estudiarse adecuadamente en este ámbito (AU)