[Hypersensitivity reactions to non-steroidal anti-inflammatory drugs and tolerance to alternative drugs]. / Reacciones de hipersensibilidad a antiinflamatorios no esteroideos y su tolerancia a fármacos alternativos.

INTRODUCTION: Hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAIDs) are the most common reactions to drugs. The prevalence varies from 0.6 to 5.7% in general population, but there are no data available in children. The aim of this study is to determine the frequency of patients diagnosed with hypersensitivity to NSAIDs, and describe their clinical characteristics, type of hypersensitivity, and tolerance to alternative drugs. METHODS: Retrospective study was conducted on children with suspected hypersensitivity to NSAIDs from January 2012 to December 2013. The diagnosis was confirmed by oral drug provocation test (DPT) to the drug involved in the group with a history of one episode, while in the group with a history of more than one episode with the same drug the diagnosis was based on clinical data. Subsequently, a DPT with acetylsalicylic acid (ASA) was done in order to classify hypersensitivity into selective or multiple. In those cases with a positive result, a DPT was performed with alternative drugs. RESULTS: Out of a total of 93 children studied, 26 were diagnosed with hypersensitivity to NSAIDs: 7 confirmed by oral DPT, and 19 based on clinical data. Multiple hypersensitivity was diagnosed in 50% of patients. Ibuprofen was involved in all reactions. The most common clinical manifestation was angioedema (44%). Acetaminophen was the best tolerated alternative drug. CONCLUSIONS: More than one quarter (28%) of the population studied was diagnosed with hypersensitivity to NSAIDs, and 50% had multiple hypersensitivity. Acetaminophen is a safe alternative in children with hypersensitivity to NSAIDs. Meloxicam may be an alternative in cases that do not tolerate acetaminophen.

Perioperative anaphylactic reactions: Review and procedure protocol in paediatrics.

Perioperative anaphylactic reactions are immediate, hypersensitive reactions that are potentially life-threatening resulting from a sudden release of mediators from mast cells and basophiles, due to either immune (IgE or non-IgE mediated) or non-immune mechanisms. The most frequent causing agents are neuromuscular blocking agents (NMBAs), latex and antibiotics, with latex being the first cause in paediatrics. With regard to perioperative anaphylactic reactions, the usual early signs and symptoms of an anaphylactic reaction could be overlooked or erroneously interpreted and non-severe anaphylaxis could go undetected, with a risk of more severe reactions in the future. Using the data registered on the anaesthesia sheet, it is essential to establish a chronological relationship between drugs and/or substances administered and the reaction observed. An elevated level of tryptase confirms an anaphylactic reaction, but this does not usually increase in the absence of compromised circulation. An allergy study should be carried out preferably between 4 and 6 weeks after the reaction, using a combination of specific IgE, skin and controlled exposure tests (if indicated). Test sensitivity is good for NMBAs, latex, antibiotics, chlorhexidine, gelatine and povidone, and poor for barbiturates, opiates (these can give false positives since they are histamine releasers) and benzodiazepines. Special preventive measures should be taken, especially in the case of latex. We present the maximum concentrations recommended for skin tests, the recommended dosage to treat anaphylactic reactions in paediatrics and a procedure algorithm for the allergological study of these reactions.

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.

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.

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.

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).

El óxido nítrico exhalado / Exhaled nitric oxide

El óxido nítrico es una molécula que en condiciones normales se sintetiza a partir de la L-arginina, merced a la acción de las denominadas ONS-c (oxido-nítrico sintetasas constitutivas) en distintas células, en cantidades muy escasas. Se comporta como un neurotransmisor modulando diferentes funciones vasculares, y del músculo liso en las vías aéreas. Sin embargo, la síntesis del ON puede también producirse mediante la acción de las denominadas ONS-i (oxido-nítrico sintetasas inducibles) cuya expresión se induce por endotoxinas y diversas citocinas pro-inflamatorias. Su actividad da lugar a grandes aumentos de carácter brusco que se asocian a situaciones de inflamación. En el asma se ha comprobado que existe un aumento de las cifras de ONE por encima de lo que presenta la población general, traduciendo una situación de inflamación de la vía aérea; característica fundamental de la patogénesis del asma, que condiciona la obstrucción y la hiperreactividad de la vía aérea que terminan de definir el asma según el concepto actual. Hasta ahora la valoración de la inflamación de las vías aéreas se hace por determinaciones séricas de otros marcadores inflamatorios que están sujetas a otras influencias y algunas son poco fiables, además de caras; o bien por determinaciones de estos marcadores en esputo inducido, o lavado broncoalveolar. La dificultad de obtención de este tipo de muestras en la edad pediátrica hace que este sistema de valoración de la inflamación no sea viable en la práctica diaria. La determinación del ONE en el aire espirado se realiza por medición por quimioluminiscencia de la síntesis de NO2 producido tras reaccionar el ON con el ozono. Esta reacción es fotoquímica y emite luz infrarroja de forma proporcional a la concentración de ON en el aire exhalado. En la exposición, trataremos de analizar el papel que juega el ONE en la patología inflamatoria del árbol respiratorio, qué técnicas podemos usar para su medida, por qué causas se puede alterar su medición y finalmente como se comporta en la alergia respiratoria. En general la literatura sobre el tema, que es extensísima, adolece de algunos defectos: disparidad de métodos de recogida de muestras de aire exhalado, diferentes situaciones patológicas en las que se determina el ONE (por ejemplo: pacientes tratados con corticoides inhalados y vírgenes de tratamiento corticoideo), grupos de pacientes pequeños, y todo ello en conjunto dificulta la comprensión del valor de la determinación del ONE en la práctica diaria. Pero de ningún modo hace que nos parezca de poca utilidad, sino al contrario: reafirma la necesidad de estudiar el comportamiento de los niveles de ONE en el asma, tanto en situaciones basales como en relación con el tratamiento de esta enfermedad (AU)

Nitric oxide is a molecule that under normal conditions is synthesised from L-arginine, thanks to the action of the so called NOS-c (nitric oxide synthethise constituents) in different cells, in very small amounts. They behave like a neurotransmitter, modulating different vascular functions of the flat muscle in the aerial vias. However, the synthesis of NO can also come about by means of the action of the so called NOS-i (nitric oxide synthethise inducers) whose expression is induced by endotoxins and different pro-inflammatory cytokines. Their activity gives rise to enlargements of an abrupt nature, that are associated to inflammatory conditions. In asthma it has been proven that there is an increase in the ENO figures, which are above the normal amount that the general population have; causing an inflammatory condition of the air way; a basic characteristic of the pathogenesis of asthma, that conditions the obstruction and the hyper-reactivity of the air ways that conclude in defining asthma according to the current concept. Until now, the valuation of the inflammation of the aerial vias is done by serum determinations of other inflammatory markers that are subject to other influences and some of them are not very reliable, apart from being expensive; or by determinations of these markers in induced sputum, or bronchoalveolar ablution. The difficulty of obtain this type of samples in young children means that it is not viable to use this system to assess the inflammation for daily practice. The determination of the ENO in the expired air is carried out by the chemoluminiscence measurement of the synthesis of O2N produced after the NO reacts with the ozone. This is a photochemical reaction and emitys infrared light in proportion to the concentration of the NO in the exhaled air. In the presentation, we will try to analyze the role that the ENO plays on the inflammatory pathology of the respiratory tree; which techniques we can use to measure it; for which reasons the measurement can be altered and finally how it behaves in respiratory allergy. In general the literature on this theme, which is very extensive, shows some defects: there is a disparity in the methods used to collect exhaled air, the pathological situations which determine the ENO are different (for example: patients being treated with inhaled corticoids and people who have never been treated with corticoids) the groups of patients are small and all this together makes it difficult to understand the value of the determination of the ENO in daily practise. But this does not mean that we feel isn't useful, on the contrary: it confirms the need to study the behaviour of the ENO levels in asthma, both in basal situations as well as in relation to the treatment of this illness (AU)

Common variable immunodeficiency, insulin-dependent diabetes mellitus and celiac disease.

Common variable immunodeficiency is a disorder characterised by hypogammaglobulinemia with B-lymphocytes in peripheral blood and repeated infections. We report a child with a diagnosis of diabetes mellitus and celiac disease during lactation, and in whom common variable immunodeficiency was diagnosed at the age of 5. During evolution of the disease he presented multiple respiratory infections in spite of substitution therapy with gamma globulins. He presented pulmonary fibrosis with a pulmonary volume reduced, and a spirometric restrictive patron. Immunologically, he presents reduction in CD4 lymphoid population. He expresses the alleles DQ2 A1 0501 and B1 which are strongly associated with susceptibility to insulin-dependent diabetes mellitus and celiac disease, but don't express antigens HLA class II DR3 and DR4 that are more frequent in these entities. The main disease and all the complications had affected his curve pondostatural.