Onset of Nut Allergy in a Pediatric Cohort: Clinical and Molecular Patterns in the AFRUSEN Study.

BACKGROUND AND OBJECTIVE: Nut allergy is a growing problem, yet little is known about its onset in children. Objective: To characterize the onset of nut allergy in children in southern Europe. METHODS: The study population comprised consecutive patients up to 14 years of age who visited allergy departments with an initial allergic reaction to peanut, tree nut, or seed. The allergy work-up included a clinical history, food challenge, skin prick testing, determination of whole-extract sIgE, and ImmunoCAP ISAC-112 assay. RESULTS: Of the 271 children included, 260 were first diagnosed with nut allergy at a mean age of 6.5 years and at a mean (SD) of 11.8 (21.2) months after the index reaction. The most common culprit nuts at onset were walnut (36.5%), peanut (28.5%), cashew (10.4%), hazelnut (8.5%), pistachio (5.4%), and almond (5%). Onset of peanut allergy was more frequent in children ≤6 years and walnut in those aged >6 years (P=.032). In 65% of cases, the allergic reaction occurred the first time the patient consumed the nut, and 35% of reactions were anaphylactic. Overall, polysensitization to nuts was detected by skin prick testing in 64.9% of patients, although this rate was lower among walnut-allergic children (54.7%) and peanut-allergic children (54.1%) (P<.0001). Sensitization to 2S albumins was predominant (75%), especially Jug r 1 (52.8%), whereas sensitization to lipid transfer proteins was less relevant (37%). CONCLUSION: In the population we assessed, the onset of nut allergy occurred around 6 years of age, slightly later than that reported in English-speaking countries. Walnut was the main trigger, followed by peanut. 2S albumin storage proteins, especially Jug r 1, were the most relevant allergens. This study will help guide management and may contribute to preventive strategies in pediatric nut allergy.

Onset of Nut Allergy in a Pediatric Cohort: Clinical and Molecular Patterns in the AFRUSEN Study

Background: Nut allergy is a growing problem, yet little is known about its onset in children. Objective: To characterize the onset of nut allergy in children in southern Europe. Methods: The study population comprised consecutive patients up to 14 years of age who visited allergy departments with an initial allergic reaction to peanut, tree nut, or seed. The allergy work-up included a clinical history, food challenge, skin prick testing, determination of whole-extract sIgE, and ImmunoCAP ISAC-112 assay. Results: Of the 271 children included, 260 were first diagnosed with nut allergy at a mean age of 6.5 years and at a mean (SD) of 11.8 (21.2) months after the index reaction. The most common culprit nuts at onset were walnut (36.5%), peanut (28.5%), cashew (10.4%), hazelnut (8.5%), pistachio (5.4%), and almond (5%). Onset of peanut allergy was more frequent in children ≤6 years and walnut in those aged >6 years (P=.032). In 65% of cases, the allergic reaction occurred the first time the patient consumed the nut, and 35% of reactions were anaphylactic. Overall, polysensitization to nuts was detected by skin prick testing in 64.9% of patients, although this rate was lower among walnut-allergic children (54.7%) and peanut-allergic children (54.1%) (P<.0001). Sensitization to 2S albumins was predominant (75%), especially Jug r 1 (52.8%), whereas sensitization to lipid transfer proteins was less relevant (37%). Conclusion: In the population we assessed, the onset of nut allergy occurred around 6 years of age, slightly later than that reported in English-speaking countries. Walnut was the main trigger, followed by peanut. 2S albumin storage proteins, especially Jug r 1, were the most relevant allergens. This study will help guide management and may contribute to preventive strategies in pediatric nut allergy (AU)

Antecedentes: La alergia a frutos secos es un problema creciente. Sin embargo, existe poca información relativa al inicio de su establecimiento en la población infantil. Objetivos: Describir el debut de alergia a frutos secos en niños del sur de Europa. Métodos: Se incluyeron pacientes de hasta 14 años que acudieron de forma consecutiva a la consulta de alergia debido a una reacción inicial con cacahuete, frutos secos o semillas. El estudio alergológico incluyó realización de historia clínica, provocación oral, prueba intraepidérmica (SPT), determinación de IgE específica para extracto completo y mediante ImmunoCAP ISAC-112. Resultados: De los 271 niños incluidos, 260 se diagnosticaron de alergia a frutos secos por primera vez a los 6,5 años de media, habiendo tenido la reacción índice 11,8 (±21,2SD) meses antes. Los frutos secos responsables en el debut fueron nuez (36,5%), cacahuete (28,5%), anacardo (10,4%), avellana (8,5%), pistacho (5,4%) y almendra (5%). La instauración de la alergia a cacahuete fue más frecuente en niños ≤6 años y para nuez en >6 años (p=0,032). En el 65% de los casos, la reacción alérgica sucedió en la primera vez en que el paciente consumía el fruto seco, y el 35% de las reacciones fueron anafilaxia. En conjunto, la polisensibilización a frutos secos se identificó en el 64,9% de los pacientes, aunque este porcentaje fue significativamente inferior en niños alérgicos a nuez (54,7%) y cacahuete (54,1%) (p<0,0001). La sensibilización a albúminas 2S fue predominante (75%), especialmente a Jug r 1 (52,8%), mientras que la identificación de LTP fue menos relevante (37%). Conclusión: En nuestra población, el debut de alergia a frutos secos sucedió alrededor de los 6 años de edad, ligeramente más tardío al reportado en países anglosajones. La nuez fue el principal desencadenante, seguido de cacahuete, y las albúminas de almacenamiento 2S, especialmente Jug r 1, fueron los alérgenos más relevantes (AU)

Heterogeneity in allergy to mollusks: a clinical-immunological study in a population from the North of Spain

Background: Allergy to mollusks has been the focus of fewer studies than allergy to crustaceans. Furthermore, allergy to mollusks is less well characterized. Objectives: To describe the clinical characteristics of mollusk-allergic patients, to identify the responsible allergens, and to assess crossreactivity. Methods: We performed a prospective multicenter study including 45 patients with mollusk allergy, which was diagnosed based on a suggestive clinical history and a positive skin test result with the agent involved. Fractions were identified using SDS-PAGE and immunoblotting. The proteins responsible were subsequently identified using mass spectrometry. ELISA inhibition studies were performed with mollusks, dust mites, and crustaceans. Results: We found that 25 patients (55%) were allergic to cephalopods, 14 (31%) to bivalves, and 11 (24%) to gastropods. Limpet was the third most frequent cause of allergy (15% of cases). In 31 patients (69%), the manifestation was systemic; 10 (22%) exhibited oral allergy syndrome, and 7 (15%) experienced contact urticaria. Most major allergens were found between 27 kDa and 47 kDa. ELISA inhibition assays revealed a high degree of inhibition of cephalopods and bivalves from all the groups of mollusks, mites, and crustaceans. Mass spectrometry identified tropomyosin, actin, and myosin as the major allergens. Conclusions: Cephalopods, especially squid, are the mollusks that most frequently trigger allergic symptoms. The very frequent occurrence of allergy to limpets is striking, given their low consumption in our area. It is worth highlighting the heterogeneity observed, exemplified by the gastropods. Tropomyosin appears to be responsible for the high cross-reactivity found between mollusks, mites, and crustaceans. Three new mollusk allergens were also identified, namely, actin, enolase, and a putative C1q domain-containing protein (AU)

Introducción: La alergia a moluscos ha sido menos estudiada y está peor caracterizada que la alergia a crustáceos. Objetivo: Describir las características clínicas de pacientes alérgicos a moluscos, identificar los alérgenos responsables y estudiar la reactividad cruzada entre ellos. Métodos: Estudio multicéntrico, prospectivo. Se incluyen 45 pacientes con alergia a moluscos, definida como una clínica sugestiva y prueba cutánea positiva con el molusco sospechoso. Se identificaron las bandas alergénicas mediante SDS-PAGE e inmunodetección. Las proteínas responsables se identificaron utilizando espectrometría de masas. Se realizaron ensayos de inhibición de ELISA entre moluscos, ácaros y crustáceos. Resultados: Veinticinco (55%) de los pacientes eran alérgicos a cefalópodos, 14 (31%) a bivalvos y 11 (24%) a gasterópodos. La lapa resultó ser la tercera causa de alergia (15% de los casos). Los síntomas fueron sistémicos en 31 pacientes (69%), diez (22%) tuvieron síndrome de alergia oral y siete (15%) urticaria de contacto. La mayoría de las bandas alergénicas estaban entre 27 y 47 kDa. Los ensayos de inhibición de ELISA mostraron un alto grado de inhibición de cefalópodos y bivalvos por parte de moluscos, ácaros y crustáceos. Mediante espectometría de masas se identificaron tropomiosina, actina y miosina como los alérgenos mayoritarios. Conclusiones: Los moluscos que con más frecuencia provocan reacciones alérgicas son los cefalópodos, especialmente el calamar. Llama la atención la elevada frecuencia de alergia a la lapa, a pesar de su bajo consumo. También hay que resaltar la heterogeneidad observada, por ejemplo en los gasterópodos. La tropomiosina parece ser responsable de la elevada reactividad cruzada encontrada entre moluscos, ácaros y crustáceos. Se han identificado tres nuevos alérgenos en los moluscos: actina, enolasa y putative C1q domain-containing protein (AU)

Improving anaphylaxis management in a pediatric emergency department.

BACKGROUND: The management of anaphylaxis in pediatric emergency units (PEU) is sometimes deficient in terms of diagnosis, treatment, and subsequent follow-up. The aims of this study were to assess the efficiency of an updated protocol to improve medical performance, and to describe the incidence of anaphylaxis and the safety of epinephrine use in a PEU in a tertiary hospital. METHODS: We performed a before-after comparative study with independent samples through review of the clinical histories of children aged <14 years old diagnosed with anaphylaxis in the PEU according to the criteria of the European Academy of Allergy and Clinical Immunology (EAACI). Two allergists and a pediatrician reviewed the discharge summaries codified according to the International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) as urticaria, acute urticaria, angioedema, angioneurotic edema, unspecified allergy, and anaphylactic shock. Patients were divided into two groups according to the date of implantation of the protocol (2008): group A (2006-2007; the period before the introduction of the protocol) and group B (2008-2009; after the introduction of the protocol). We evaluated the incidence of anaphylaxis, epinephrine administration, prescription of self-injecting epinephrine (SIE), other drugs administered, the percentage of admissions and length of stay in the pediatric emergency observation area (PEOA), referrals to the allergy department, and the safety of epinephrine use. RESULTS: During the 4 years of the study, 133,591 children were attended in the PEU, 1673 discharge summaries were reviewed, and 64 cases of anaphylaxis were identified. The incidence of anaphylaxis was 4.8 per 10,000 cases/year. After the introduction of the protocol, significant increases were observed in epinephrine administration (27% in group A and 57.6% in group B) (p = 0.012), in prescription of SIE (6.7% in group A and 54.5% in group B) (p = 0.005) and in the number of admissions to the PEOA (p = 0.003) and their duration (p = 0.005). Reductions were observed in the use of corticosteroid monotherapy (29% in group A, 3% in group B) (p = 0.005), and in patients discharged without follow-up instructions (69% in group A, 22% in group B) (p = 0.001). Thirty-three epinephrine doses were administered. Precordial palpitations were observed in one patient. CONCLUSION: The application of the anaphylaxis protocol substantially improved the physicians' skills to manage this emergency in the PEU. Epinephrine administration showed no significant adverse effects.

[Henna tattooing in children: natural or temporary?]. / Tatuaje de henna en niños: ¿natural y temporal?

BACKGROUND: Tattoos of natural red/brown henna obtained from the indigenous tree Lawsonnia have been traditionally performed with a few side-effects. Nowadays black henna tattoos are usually performed even in children. The addition of several chemical agents to improve its cosmetic properties has increased the risk of developing contact dermatitis after exposure. Our aim is to determine the causative agents of contact dermatitis in two children wearing henna tattoos. MATERIAL AND METHODS: Case 1: A 12-year-old girl with no atopy presented local vesicles 10 hours after a black henna tattoo was applied. She had presented similar symptoms with a previous tattoo. Case 2: A 7-year-old atopic boy presented vesicles 2 weeks after a black henna tattoo was applied. He had dyed his hair previously without side effects. Both patients cured, after 3-4 weeks of treatment with topic corticosteroids, with residual hypo-pigmentation. Skin prick test with natural and commercial henna and epicutaneous test with TRUE-TEST, PABA derivatives compounds tests, textile dyes and natural and commercial henna were performed. RESULTS: The epicutaneous tests were positive for p-Metilaminophenol, p-Aminobencene, p-Phenilendiamine and p-Toluenodiamine in both patients. The first patient had also positive tests for Benzocaine, Hydroquinone, Isobutyl p-aminobenzoate, Yellow 1 and Orange 1 disperse; the second one for Red 1 and Orange 1 disperse. In both cases the prick and epicutaneous tests for henna were negative. CONCLUSIONS: Two children presented contact dermatitis after black henna tattoo due to added additives such as paraphenilendiamine.

[Food allergy in the XXI century]. / La alergia alimentaria en el siglo XXI.

Food allergy is a clinical state of high frequency and possible risk to life. This article reviews the foodstuffs most often responsible for serious reactions, including data from the Autonomous Community of Navarre. Given that dietetic elimination is the primordial long term treatment for food allergy, its difficulties, limitations and risks are analyzed. Finally, we set out the new perspectives offered by technology in the field of food allergy, both in the production of hypoallergens and in the development of new forms of immunotherapy.

[Allergy to Anisakis simplex]. / Alergia a Anisakis simplex.

Anisakis simplex is a parasite, belonging to the Anisakidae family. The life cycle of the parasite can include one or more intermediary hosts, their final hosts being marine mammals or large fish, in which the larvae develop until the adult stage is reached. Man is an accidental host who acquires the larvae by eating raw or undercooked fish. Since the mid-50s, when the first case studies were published in Holland and Japan, new cases have been emerging in different countries including Spain. Parasitization of man by the living larva is known as anisakiasis, principally giving rise to digestive symptomology, with other rare cases described of invasion of other organs such as the lung, the liver, the spleen, the pancreas, etc. Clinical pictures of allergy to IgE mediated anisakis simplex have also been described: reactions by thermostable antigens of the parasite that develop in spite of the fish being cooked or frozen, and an acute digestive parasitization with allergic symptoms called gastro-allergic anisakiasis. In the diagnosis of anisakiasis and/or allergy to Anisakis, the antecedent of the prior ingestion of fish as well as the clinical accompaniment can form basic data of considerable orientational value, and endoscopy can reveal the presence of the larvae and make possible their extraction. Besides, in cases of allergy the detection test for specific IgE facing Anisakis simplex, and cutaneous tests with fish should be carried out. The best treatment for avoiding this parasitization is prophylactic, avoiding the consumption of raw or undercooked fish, while a fish free diet is necessary in cases of true allergy to the thermostable proteins of the parasite.

[Epicutaneous test with inhalers in the study of atopic dermatitis]. / Test epicutáneos con inhalantes en el estudio de la dermatitis atópica.

In some 80% of patients with atopic dermatitis, the presence of specific IgE is found when facing food or environmental allergens. It has also been demonstrated in a sub-group of patients with atopic dermatitis that the dermatitis lesions are exacerbated following the ingestion or inhalation of allergens, and that they improve with reduction of exposure to allergens. Although the prick method and the determination of specific IgE in serum are highly sensitive techniques, epicutaneous tests, applying the allergen directly to the skin, might be the ideal diagnostic method since they reproduce the characteristic inflammatory response of the disease on the affected organ itself, the skin. However, there is great variability in the results obtained through epicutaneous tests with aeroallergens, basically due to methodological differences, which are reviewed in this paper. Finally, we present the results of carrying out epicutaneous tests with inhalant allergens on our patients with atopic dermatitis and controls, where some 27% of positive patches were obtained, basically with acari, and in those patients with more severe dermatitis, without there being complete concordance with the prick technique. For this reason, the epicutaneous test appears to be a method of allergological diagnosis that might be useful and complementary to the routine techniques of the prick method and the determination of specific IgE in serum, but it is in need of suitable standardization.

[From rhinitis to asthma, one or two diseases?]. / De la rinitis al asma: ¿una o dos enfermedades?

Rhinitis and asthma commonly coexist in allergic patients. This observation might be attributable to their coexistence in time, but it is also possible that both diseases are the opposite poles of a single disease affecting the respiratory system, or even an anomalous systemic immune response to the allergen. Nose-lung interactions have been widely studied from epidemiological, physiopathological, aetiological and pharmacological aspects. In the present article we review this topic and its main clinical implications.

[Latex allergy. Clinical manifestations in the general population and reactivity crossed with foodstuffs]. / Alergia al látex. Manifestaciones clínicas en la población general y reactividad cruzada con alimentos.

Because of widespread latex manufacturing in the last decades, latex allergy has become an important clinical problem, not only in high-risk groups (health-workers) but also among the general population. Latex is used to produce a large variety of natural rubber products (medical equipment, household gloves, condoms, balls and balloons, footwear, baby pacifiers...) employed in the ordinary life, with high risk for patients allergic to latex. Among general population, children affected by myelomeningocele or spina bifida, have a higher risk to develop latex allergy. Clinical manifestations range from local reactions(contact dermatitis, urticaria), rhino-conjunctivitis, asthma, pharyngeal edema to severe systemic reactions such anaphylactic shock. Furthermore, latex can crossreact with some plant foods, and patients suffering from latex allergy often associate food allergy.

[Anaphylaxis]. / Anafilaxia.

Anaphylaxis is a potentially mortal, underdiagnosed clinical picture. The most frequent triggering agents are drugs and foodstuffs. The first therapeutic option, adrenaline, although clearly indicated, is not carried out with the desired frequency due basically to the high number of cases of anaphylaxis that are not diagnosed as such. In patients with a first episode of anaphylaxis, posterior aetiological diagnosis is crucial to avoid the appearance of new episodes. The only case of anaphylaxis in which immunotherapy with the allergen must be evaluated, is that in which the causal agent is the poison of hymenopters.

[Immunotherapy with grouped doses]. / Inmunoterapia con pautas agrupadas.

Once the efficacy and safety of immunotherapy with allergen extracts has been shown, recently it has become evident the need for perfecting those aspects of the treatment that can be improved, such as its dosage form. The conventional dosage of subcutaneous immunotherapy in the phase of dose increase is slow in reaching an efficient level. For this reason other alternative dosages to the conventional one have been tried out, such as grouped dosages, which shorten this period of dose increase. On condition that the safety of the treatment is guaranteed, these doses offer the advantages of reducing the economic cost and the time involved, of reducing the discomfort of the treatment and of improving the patient's adherence to the treatment, and possibly of reaching clinical efficacy more rapidly. Nonetheless, it is not easy to determine the suitable dosage of administration (the shortest and with the least number of adverse reactions) and this article reviews the existing problems when it comes to designing these grouped doses. Finally, we present the results of a comparative study between the conventional dose and a grouped dose, with a double blind design, carried out by us, which shows that the grouped dose is quicker in achieving the desired clinical efficacy, shortens the times of reduction of cutaneous sensitivity to the allergen and of modification of the immunological parameters, all with a low frequency of adverse reactions that is similar to that registered with the conventional dosage.

[Local immunotherapy]. / Inmunoterapia local.

Specific immunotherapy, together with avoidance of the allergen and symptomatic treatment, forms part of the treatment of allergic pathology. The oldest, best known and most studied form is subcutaneous immunotherapy (SCIT), whose efficacy, both in the short and the long term, has been widely demonstrated in numerous studies. However, in spite of having been shown to be safe, it is not free of adverse effects and must be administered under the supervision of medical personnel. This has encouraged the search for new ways of administration of similar efficacy, with a good safety profile and good adherence on the patient's side. Sublingual immunotherapy (SLIT) is the most relevant of the different alternatives studied. In this alternative the antigen is administered in the form of drops under the tongue. There are different dosages of administration depending on the allergen involved. The optimum treatment dose has still to be determined, at present a wide range of dosages are found in comparison with subcutaneous immunotherapy. Its mechanism of action is little known although immunological changes have been observed in different studies. SLIT has shown a good safety profile with scarce secondary effects, normally of a local character. Similarly, different clinical tests have been carried out in which its efficacy has been shown in the treatment of respiratory allergy both in children and in adults. For this reason, although there are still unresolved data concerning this way of administering the immunotherapy, it has been proposed by the WHO as a valid alternative to SCIT.

Test epicutáneos con inhalantes en el estudio de la dermatitis atópica / Epicutaneous test with inhalers in the study of atopic dermatitis

En un 80 por ciento de pacientes con dermatitis atópica se demuestra la presencia de IgE específica frente a alergenos alimentarios o ambientales. También se ha demostrado la exacerbación de las lesiones de la dermatitis tras ingestión o inhalación de alergenos y su mejoría al reducir la exposición alergénica en un subgrupo de pacientes con dermatitis atópica. Aunque el prick y la determinación de IgE específica en suero son técnicas muy sensibles, las pruebas epicutáneas aplicando el alergeno directamente en la piel podrían ser el método diagnóstico ideal ya que reproducen la respuesta inflamatoria característica de la enfermedad en el propio órgano de choque que es la piel. Sin embargo, existe gran variabilidad en los resultados obtenidos mediante pruebas epicutáneas con aeroalergenos, debido fundamentalmente a diferencias metodológicas, que se revisan en este trabajo. Por último, presentamos los resultados de realizar pruebas epicutáneas con alergenos inhalantes a nuestros pacientes con dermatitis atópica y controles, obteniendo un 27 por ciento de parches positivos, fundamentalmente con ácaros y en aquellos pacientes con dermatitis más grave sin que exista una completa concordancia con la técnica del prick. Por ello, las pruebas epicutáneas parecen un método de diagnóstico alergológico que puede ser útil y complementario a las técnicas de rutina como el prick o la determinación de IgE específica en suero, pero queda pendiente su adecuada estandarización (AU)

La alergia alimentaria en el siglo XXI / Food allergy in the XXI century

La alergia alimentaria es una situación clínica de alta prevalencia y posible riesgo vital. En este artículo se revisan los alimentos más frecuentemente responsables de las reacciones graves, incluyendo datos de la Comunidad Autónoma de Navarra. Puesto que la dieta de eliminación constituye el punto primordial del tratamiento a largo plazo de la alergia alimentaria, se analizan sus dificultades, limitaciones y riesgos. Por último se exponen las nuevas perspectivas que ofrece la tecnología en el campo de la alergia a alimentos, tanto en la producción de alimentos hipoalergénicos como en el desarrollo de nuevas formas de inmunoterapia (AU)

Alergia a Anisakis simplex / Allergy to Anisakis simplex

El Anisakis simplex es un parásito perteneciente a la familia Anisakidae. El ciclo vital del parásito puede incluir uno o más huéspedes intermediarios, siendo sus huéspedes definitivos mamíferos marinos y grandes peces en los cuales la larva se desarrolla hasta alcanzar el estadio adulto. El hombre es un huésped accidental que adquiere las larvas al ingerir pescado crudo o poco cocinado. Desde mediados de los años cincuenta en que se publicaron los primeros casos en Holanda y Japón, se han ido comunicando nuevos casos en diferentes países entre ellos España. La parasitación del hombre por la larva viva se conoce como anisakiasis, dando lugar a sintomatología digestiva principalmente, describiéndose también casos raros de invasión de otros órganos como pulmón, hígado, bazo, páncreas, etc. También han sido descritos cuadros de alergia a Anisakis simplex IgE mediadas: reacciones por antígenos termoestables del parásito que se desarrollan a pesar de que el pescado se consuma cocinado o congelado y una parasitación aguda digestiva con síntomas alérgicos llamada anisakiasis gastro-alérgica. En el diagnóstico de anisakiasis y/o alergia a Anisakis el antecedente de la ingesta previa de pescado así como la clínica acompañante pueden ser datos bastante orientativos y la realización de endoscopia puede demostrar la presencia de las larvas y permitir su extracción. Además en los casos de alergia deben realizarse test para la detencción de IgE específica frente a Anisakis simplex y pruebas cutáneas con pescado. El mejor tratamiento para evitar esta parasitación es profiláctico, evitando la ingesta de pescado crudo o poco cocinado, siendo necesaria una dieta de exclusión de pescado en los casos de verdadera alergia a las proteínas termoestables del parásito (AU)