Dispositivos médicos en pacientes diabéticos y dermatitis de contacto / Medical Devices in Patients With Diabetes and Contact Dermatitis

El desarrollo y comercialización de los sensores de glucosa y las bombas de insulina han supuesto una revolución en el control de los pacientes diabéticos. En los últimos años se han detectado múltiples casos de dermatitis de contacto relacionados con estos dispositivos médicos, con el creciente interés sobre los alérgenos responsables de la sensibilización. Isobornil acrilato fue sin duda el alérgeno principal del dispositivo FreeStyle, motivando al fabricante a modificar la composición eliminando este alérgeno. Curiosamente, este alérgeno está presente en casi todos los sensores comercializados. La colofonia y derivados del ácido abiético desempeñan un papel relevante en cuanto al adhesivo. Recientemente aparecen nuevos componentes identificados como alérgenos, no comercializadas, como el dipropilene glicol diacrilato, la N,N-dimetilacrilamida, o el metacrilato de trietilenglicol, que están siendo foco de estudio. El impacto positivo que tiene el uso de estos dispositivos puede verse mermado por la sensibilización a uno de sus ingredientes, obligando en ocasiones a abandonar el dispositivo, y por ende, restando calidad de vida. El dermatólogo debe posicionarse respecto al estudio dirigido de estos pacientes, dando soporte a los servicios de endocrinología, con la finalidad de orientar tanto el cuidado de la piel como las alternativas posibles, especialmente con la colaboración de los fabricantes.(AU)

The development and commercialization of glucose sensors and insulin pumps has revolutionized the management of diabetes. These devices have been linked to multiple cases of contact dermatitis in recent years, however, giving rise to a growing interest in identifying the sensitizing allergens. Isobornyl acrylate was clearly identified as one of the main allergens responsible for contact dermatitis among users of the FreeStyle glucose sensor and was subsequently removed from the product ingredients. Remarkably, however, it is still used in most other sensors on the market. The common adhesive ingredients colophony and abietic acid derivatives have also been shown to be sensitizing agents. New components under study, such as dipropylene glycol diacrylate, N,N-dimethylacrylamide, and triethylene glycol methacrylate have recently been identified as allergens, though they are not commercially available for clinical testing. The benefits offered by glucose sensors and insulin pumps may be offset by sensitization to product ingredients, in some cases forcing discontinuation and diminishing quality of life. Dermatologists should play a role in this clinical and research scenario, offering case-by-case guidance to endocrinologists on skin care and possible alternatives for patients with glucose sensors and insulin pumps who develop contact dermatitis. They should also collaborate with the manufacturers developing these devices.(AU)

[Translated article] Medical Devices in Patients With Diabetes and Contact Dermatitis / Dispositivos médicos en pacientes diabéticos y dermatitis de contacto

El desarrollo y comercialización de los sensores de glucosa y las bombas de insulina han supuesto una revolución en el control de los pacientes diabéticos. En los últimos años se han detectado múltiples casos de dermatitis de contacto relacionados con estos dispositivos médicos, con el creciente interés sobre los alérgenos responsables de la sensibilización. Isobornil acrilato fue sin duda el alérgeno principal del dispositivo FreeStyle, motivando al fabricante a modificar la composición eliminando este alérgeno. Curiosamente, este alérgeno está presente en casi todos los sensores comercializados. La colofonia y derivados del ácido abiético desempeñan un papel relevante en cuanto al adhesivo. Recientemente aparecen nuevos componentes identificados como alérgenos, no comercializadas, como el dipropilene glicol diacrilato, la N,N-dimetilacrilamida, o el metacrilato de trietilenglicol, que están siendo foco de estudio. El impacto positivo que tiene el uso de estos dispositivos puede verse mermado por la sensibilización a uno de sus ingredientes, obligando en ocasiones a abandonar el dispositivo, y por ende, restando calidad de vida. El dermatólogo debe posicionarse respecto al estudio dirigido de estos pacientes, dando soporte a los servicios de endocrinología, con la finalidad de orientar tanto el cuidado de la piel como las alternativas posibles, especialmente con la colaboración de los fabricantes.(AU)

The development and commercialization of glucose sensors and insulin pumps has revolutionized the management of diabetes. These devices have been linked to multiple cases of contact dermatitis in recent years, however, giving rise to a growing interest in identifying the sensitizing allergens. Isobornyl acrylate was clearly identified as one of the main allergens responsible for contact dermatitis among users of the FreeStyle glucose sensor and was subsequently removed from the product ingredients. Remarkably, however, it is still used in most other sensors on the market. The common adhesive ingredients colophony and abietic acid derivatives have also been shown to be sensitizing agents. New components under study, such as dipropylene glycol diacrylate, N,N-dimethylacrylamide, and triethylene glycol methacrylate have recently been identified as allergens, though they are not commercially available for clinical testing. The benefits offered by glucose sensors and insulin pumps may be offset by sensitization to product ingredients, in some cases forcing discontinuation and diminishing quality of life. Dermatologists should play a role in this clinical and research scenario, offering case-by-case guidance to endocrinologists on skin care and possible alternatives for patients with glucose sensors and insulin pumps who develop contact dermatitis. They should also collaborate with the manufacturers developing these devices.(AU)

[Translated article] Medical Devices in Patients With Diabetes and Contact Dermatitis.

The development and commercialization of glucose sensors and insulin pumps has revolutionized the management of diabetes. These devices have been linked to multiple cases of contact dermatitis in recent years, however, giving rise to a growing interest in identifying the sensitizing allergens. Isobornyl acrylate was clearly identified as one of the main allergens responsible for contact dermatitis among users of the FreeStyle glucose sensor and was subsequently removed from the product ingredients. Remarkably, however, it is still used in most other sensors on the market. The common adhesive ingredients colophony and abietic acid derivatives have also been shown to be sensitizing agents. New components under study, such as dipropylene glycol diacrylate, N,N-dimethylacrylamide, and triethylene glycol methacrylate have recently been identified as allergens, though they are not commercially available for clinical testing. The benefits offered by glucose sensors and insulin pumps may be offset by sensitization to product ingredients, in some cases forcing discontinuation and diminishing quality of life. Dermatologists should play a role in this clinical and research scenario, offering case-by-case guidance to endocrinologists on skin care and possible alternatives for patients with glucose sensors and insulin pumps who develop contact dermatitis. They should also collaborate with the manufacturers developing these devices.

Cosensitization to the 3 Nonhomologous Major Cashew Allergens Ana o 1, Ana o 2, and Ana o 3 Is Caused by IgE Cross-reactivity

Background: Cashew nuts often cause strong allergic reactions, which are even more severe than those of peanuts. Ana o 1 (vicilin), Ana o 2 (legumin), and Ana o 3 (2S albumin) are major cashew allergens. Cosensitization to all 3 nonhomologous cashew nut allergens has been observed. We hypothesize that this might be due to IgE cross-reactivity. Methods: IgE cross-inhibitions were performed with Ana o 1-3 using serum samples from cashew nut–allergic patients. The related hazelnut allergens Cor a 11, 9, and 14 were used as controls. For comparison, IgE cross-reactivity between the hazelnut allergens was investigated using serum samples from hazelnut-allergic patients. Results: The median percentages of cross-inhibition between Ana o 1, 2, and 3 were 84%-99%. In comparison, the median cross- inhibition values between hazelnut allergens were 33%-62%. The IC50 values revealed the highest IgE affinity to be to Ana o 3 and Cor a 14. Hazelnut legumin Cor a 9 inhibited IgE binding to Ana o 1, 2, and 3, with median percentages of 75%, 56%, and 48%, respectively. No cross-reactivity was observed between allergenic vicilins or between 2S albumins from cashew and hazelnut. Potentially cross-reactive peptides of Ana o 3 identified in silico overlapped with previously reported IgE epitopes of all 3 allergens. Conclusion: IgE with high affinity to Ana o 3 that cross-reacts with the other 2 major nonhomologous cashew nut allergens might be responsible for the high allergenic potency of cashew nut. These cross-reactive IgE types comprise the major fraction of specific IgE in cashew-allergic patients and might be responsible for cross-reactivity between unrelated tree nuts (AU)

Antecedentes: Los anacardos suelen provocar fuertes reacciones alérgicas, que son incluso más graves que las del maní. Ana o 1 (vicilina), Ana o 2 (legumina) y Ana o 3 (albúmina 2S) son los principales alérgenos del anacardo. Se ha observado cosensibilización a los 3 alérgenos no homólogos del anacardo. Nuestra hipótesis es que esto podría deberse a la reactividad cruzada de la IgE. Métodos : Se realizaron inhibiciones cruzadas de IgE con Ana o 1-3 utilizando muestras de suero de pacientes alérgicos al anacardo. Como controles se utilizaron los alérgenos de avellana relacionados Cor a 11, 9 y 14. A modo de comparación, se investigó la reactividad cruzada de IgE entre los alérgenos de la avellana utilizando muestras de suero de pacientes alérgicos a la avellana. Resultados : Los porcentajes medios de inhibición cruzada entre Ana o 1, 2 y 3 fueron del 84% al 99%. En comparación, los valores medios de inhibición cruzada entre alérgenos de avellana fueron del 33% al 62%. Los valores de IC50 revelaron que la mayor afinidad de IgE era Ana o 3 y Cor a 14. La legumina de avellana Cor a 9 inhibió la unión de IgE a Ana o 1, 2 y 3, con porcentajes medios de 75%, 56% y 48%. , respectivamente. No se observó reactividad cruzada entre vicilinas alergénicas ni entre albúminas 2S de anacardo y avellana. Los péptidos potencialmente de reacción cruzada de Ana o 3 identificados in silico se superpusieron con epítopos de IgE previamente informados de los 3 alérgenos. Conclusión : La IgE con alta afinidad por Ana o 3 que reacciona de forma cruzada con los otros 2 alérgenos principales no homólogos del anacardo podría ser responsable de la alta potencia alergénica del anacardo. Estos tipos de IgE de reacción cruzada comprenden la fracción principal de IgE específica en pacientes alérgicos al anacardo y podrían ser responsables de la reactividad cruzada entre frutos secos no relacionados (AU)

Valoración del impacto de la legislación argentina sobre alérgenos alimentarios: cinco años de una travesía con aciertos y desafíos / Assessment of the impact of the argentine legislation on food allergens: five years of a journey with successes and challenges / Avaliação do impacto da legislação argentina sobre alérgenos alimentares: cinco anos de uma caminho de desafios e sucessos

Resumen Las alergias alimentarias representan un problema de salud pública. La declaración de alérgenos en el rótulo implicó un avance fundamental para la gestión del riesgo, ya que evitar el alimento desencadenante mediante el rotulado adecuado constituye actualmente una medida insustituible de cuidado para la población susceptible. Se realizó una valoración del impacto de la legislación nacional en referencia a la declaración de alérgenos alimentarios entre 2017 y 2022. Se utilizaron los motores de búsqueda interna de la Administración Nacional de Medicamentos, Alimentos y Tecnología Médica (ANMAT) para los retiros de productos alimenticios del mercado y se contrastó como herramienta de medición indirecta para la valoración del impacto de la implementación del Artículo 235 séptimo del Código Alimentario Nacional (CAA). Se analizaron 43 productos (galletitas, fideos, chocolates, alimentos a base de vegetales). El 53,5% (23 sobre un total de 43) presentaba declaración de alérgenos. El 70% de los mismos (16 sobre un total de 23) fueron categorizados "con inconsistencias" y el 14% (6 productos de 43) utilizaba etiquetado precautorio. El paradigma reactivo del control de alimentos sobresalió por sobre el de las auditorías, los programas de monitoreo y, en suma, sobre los programas de prevención, ya que el sistema se activó fundamentalmente por la vía reactiva de las denuncias. Esto representó un 72% de los productos categorizados.

Abstract Food allergies represent a public health problem. The declaration of allergens on the label implied a fundamental advance for risk management, since avoiding the triggering food through proper labelling is currently an irreplaceable measure of care for the susceptible population. An assessment of the impact of the national legislation was carried out in reference to the declaration of food allergens between 2017 and 2022. The ANMAT internal search engines were used for the withdrawals of food products from the market and contrastlised as an indirect measurement tool for the impact assessment of the implementation of Section 235 seventh of the Argentine Food Code (CAA, for its acronym in Spanish). Forty-three products (biscuits, noodles, chocolates, vegetable-based foods) were analysed. The allergen declaration was present in 53.5% (23 out of a total of 43). Some inconsistencies were present in 70% of them (16 out of a total of 23) and 14% (6 products out of 43) used precautionary labelling. The reactive paradigm of food control stood out above that of audits, monitoring programmes and, in short, prevention programmes, since the system was activated fundamentally through the reactive route of complaints. This represented 72% of the categorised products.

Resumo As alergias alimentares representam um problema de saúde pública. A declaração de alérgenos no rótulo envolveu um avanço fundamental para a gestão do risco, visto que evitar os alimentos que desencadeiam as alergias, por meio de uma rotulagem adequada, é atualmente uma medida insubstituível de cuidado para a população suscetível. Foi realizada uma avaliação do impacto da legislação nacional referida à declaração de alérgenos alimentares entre 2017 e 2022. Os motores de busca interna da ANMAT (Administração Nacional de Medicamentos, Alimentos e Tecnologia Médica) foram utilizados para as retiradas de produtos alimentares do mercado e contrastados como uma ferramenta indireta de medição para a avaliação do impacto da aplicação do artigo 235 sétimo, do CAA (Código Alimentar Nacional). Foram analisados 43 produtos (biscoitos, macarrão, chocolates, alimentos à base de vegetais). 53,5% (23 de um total de 43) apresentavam declaração de alérgenos, 70% deles (16 de um total de 23) foram categorizados "com inconsistências" e 14% (6 produtos de 43) utilizavam rotulagem de precaução. Destacou-se o paradigma "reativo" do controle de alimentos por sobre o controle das auditorias, dos programas de monitoramento e, em resumo, dos programas de prevenção, visto que o sistema foi ativado fundamentalmente pela via reativa das reclamações. Isso representou 72% dos produtos categorizados.

ESTUDIO COMPARATIVO DE LA DECLARACIÓN DE ALÉRGENOS Y FRASES DE ADVERTENCIA EN RÓTULOS DE ALIMENTOS ENTRE LOS AÑOS 2019 Y 2022 / DECLARATIOM OF ALLERGENS AND WARNING PHRASES ON FOOD LABELS. COMPARATIVE STUDY BETWEEN 2019 AND 2022 YEARS

El etiquetado de alérgenos alimentarios en los productos es hoy uno de los temas que genera grandes preocupaciones en la población. Objetivo: evaluar cómo las distintas empresas se adecuaron a la legislación vigente sobre alérgenos en Argentina. Materiales y Métodos: en 2019 se relevaron 16 productos alimenticios dulces y salados que se codificaron como: ME, MN, TO, PA, GD, F, MLV, QM, BB, BT, TR, TM, PFK, BQK, CHB y CM. Para realizar la comparación de las declaraciones de alérgenos, a mediados de 2022 se volvieron a relevar los 16 productos, encontrándose tres de ellos discontinuados. El análisis del rótulo comprendió la verificación del cumplimiento de la declaración de alérgenos, uso de frases de advertencia (FA) y presentación de la información. Resultados y Discusión: en el 2019 en la declaración de alérgenos se incluyen expresiones como: "contiene gluten", en un 50% de los productos analizados. Por otro lado, en 5 de los 15 productos con FA, hay expresiones del tipo "puede contener trazas…". Asimismo, se incluye en 5 productos, al sésamo, alérgeno contemplado por legislaciones diferentes a la Argentina. Con respecto a la presencia de dióxido de azufre y sulfitos, hay dos productos que los declaran a continuación de la lista de ingredientes y otros dos productos que declaran a los sulfitos en sus frases de advertencia. Al analizar los rótulos en el 2022, el 80% de los productos analizados no presentan inconsistencias en lo que respecta a la presentación de la información. Conclusiones: en el estudio comparativo se observa una mejora en la correcta declaración de alérgenos y frases de advertencia. Sin embargo, después de más de cinco años de haber finalizado el plazo otorgado a las industrias para la adecuación de los rótulos, para una adecuada declaración de alérgenos, persisten algunos productos no conformes

The labeling of food allergens in products is today one of the issues that generates great concern in the population. Objective: was to evaluate how different companies adapted to current legislation on allergens in Argentina. Materials and methods: in 2019, sixteen sweet and salty food products were surveyed, coded as: ME, MN, TO, PA, GD, F, MLV, QM, BB, BT, TR, TM, PFK, BQK, CHB and CM. To compare the allergen declarations, in mid-2022 the sixteen products were surveyed again, finding three discontinued products. The analysis of the label included verification of compliance with the allergen declaration, use of warning phrases (FA), and presentation of information. Results and Discution: in 2019, the declaration of allergens includes expressions such as: "contains gluten", in 50% of the products analyzed. On the other hand, in five of the fifteen products with FA, there are expressions such as "may contain traces...". Likewise, it is included in five products, sesame, an allergen contemplated by legislations other than Argentina. Regarding the presence of sulfur dioxide and sulphites, there are two products that declare them below the list of ingredients and two other products that declare sulphites in their warning phrases. When analyzing the labels in 2022, 80% of the analyzed products do not present inconsistencies with regard to the presentation of the information.Conclusions: in the comparative study, an improvement is observed in the correct declaration of allergens and warning phrases.However, more than five years after the end of the period granted to the industries for the adaptation of the labels for an adequate declaration of allergens, some errors persist in them

Presença do alérgeno de soja Gly m 1 no ar em Maringá - PR / Levels of airborne soy allergen Gly m 1 in Maringá, PR, Brazil

Introdução: O conhecimento da aerobiologia local é fundamental para o alergista. Os aeroalérgenos são capazes de sensibilizar e levar ao desenvolvimento de doenças respiratórias alérgicas, portanto devem ser monitorados rotineiramente, tendo em vista possíveis mudanças locais conforme alterações climáticas, poluição e atividades agroindustriais. Objetivo: Verificar a presença e concentração do alérgeno principal da poeira da casca da soja (Gly m 1) na atmosfera da cidade de Maringá-PR e possíveis associações aos fatores climáticos. A escolha da soja deve-se a alta prevalência desta cultura no Brasil e nesta região do país. Até o presente momento, há apenas um estudo piloto feito por este mesmo grupo avaliando a presença deste alérgeno no Brasil. Métodos: Foram realizadas coletas de material atmosférico, durante o período de março de 2017 a março de 2018, durante 24 ou 48 horas distribuídas no decorrer do período, totalizando 70 amostras, das quais 10 foram excluídas por problemas técnicos de coleta. As amostras foram avaliadas pelo método ELISA (Enzyme linked immunosorbent assay ) para Gly m 1, sendo que todas as amostras apresentaram níveis detectáveis do alérgeno. Resultados: A mediana de concentração de Gly m 1 foi de 4,89 ng/m3. Os valores encontrados variaram de 0,66 ng/ m3 a 1826,1 ng/m3. Das 60 amostras analisadas, 23% delas apresentaram valores superiores a 90 ng/m3, sendo os meses de junho/2017 e março/2018 com concentrações mais elevadas. Houve correlação positiva das concentrações de Gly m 1 com as temperaturas máxima, média e mínima, umidade relativa, vento e insolação. Conclusão: Os dados evidenciam exposições constantes da população ao alérgeno do Gly m 1, por vezes em níveis elevados possivelmente capazes de gerar sensibilização e sintomas.

Introduction: Knowledge of local aerobiology is essential for allergists. Because airborne allergens can sensitize the population and lead to allergic respiratory diseases, they must be routinely monitored for the effects of climate change, pollution, and agroindustry. Objective: To verify the airborne presence and concentration of the main soy hull dust allergen (Gly m 1) in Maringá, PR, Brazil and possible associations with climatic factors. Soybeans were selected due to the high prevalence of this crop in this region. To date, only 1 pilot study (conducted by our group) has evaluated this allergen's presence in Brazil. Methods: Atmospheric material was collected between March 2017 and March 2018 in 24- or 48-hour intervals, totaling 70 samples, of which 10 were excluded due to technical problems. The samples were tested for Gly m 1 using enzyme-linked immunosorbent assay, and all samples showed detectable levels of the allergen. Results: The median concentration of Gly m 1 was 4.89 ng/m3, with values ranging from 0.66 ng/m3 to 1826.1 ng/m3. Of the 60 samples, 23% showed values > 90 ng/m3, with June 2017 and March 2018 having the highest concentrations. There was a positive correlation between Gly m 1 concentration and maximum, mean, and minimum temperatures, relative humidity, wind, and insolation. Conclusion: The data show that the population is constantly exposed to the Gly m 1 allergen, sometimes at high levels, which may lead to sensitization and symptoms.

A 5-Year Open-Label Follow-up of a Randomized Double-Blind Placebo-Controlled Trial of Intralymphatic Immunotherapy for Birch and Grass Allergy Reveals Long-term Beneficial Effects

Background: Intralymphatic immunotherapy (ILIT) is a novel, faster alternative to conventional allergen immunotherapy (AIT). Few previous studies have evaluated its long-term effects. The objective of the present study was to complete a 5-year follow-up of a randomized double-blind placebo-controlled trial of ILIT for a combination of birch and grass allergens. Methods: Fifty-eight patients with allergic rhinitis were treated with either placebo or a combination of ALK Alutard Birch and Grass 1000 SQ-U administered in 3 intralymphatic injections at 1-month intervals. A year after the vaccination, the symptoms induced by nasal provocation were significantly reduced. After 5-6 years, 20 out of 26 actively treated patients were followed up with a nasal provocation test (NPT) and seasonal registration of the combined symptom and medications score (CSMS), IgE and IgG4 levels in blood, and immunological markers in blood and lymph nodes and compared with 13 unvaccinated controls. Results: The reduction in the NPT response with ILIT at year 1 could not be convincingly reproduced at year 5. The new CSMS scores were markedly lower among the previously treated patients than among the control group. Furthermore, grass-specific IgG4 was increased, grass-specific IgE decreased, FcεR1 on basophils was reduced, and the fraction of memory T-cells in lymph nodes increased. Conclusion: The combination of seasonal clinical data and immunological parameters supports the notion of a long-lasting effect of ILIT. These data support the concept of ILIT as a good alternative to traditional AIT in pollen-induced allergic rhinitis (AU)

Antecedentes: La inmunoterapia intralinfática (ILIT) se ha propuesto como una alternativa novedosa y rápida frente a la inmunoterapia convencional con alérgenos (AIT). Muy pocos estudios han evaluado sus efectos a largo plazo. El objetivo del estudio fue completar un seguimiento de 5 años de un ensayo aleatorizado, doble ciego, controlado con placebo, previamente realizado, de ILIT con una combinación de alérgenos de abedul y gramíneas. Métodos: 58 pacientes con rinitis alérgica fueron tratados con placebo o una combinación de ALK Alutard Birch and Grass 1000 SQ-U, mediante tres inyecciones intralinfáticas administradas con intervalos de un mes. Un año después de la vacunación, los síntomas inducidos por provocación nasal se redujeron significativamente. Entre 5 y 6 años más tarde, 20 de los 26 pacientes tratados activamente fueron evaluados mediante nueva prueba de provocación nasal (NPT), registro estacional de la puntuación combinada de síntomas y consumo de medicamentos (CSMS), niveles de IgE e IgG4 en sangre y marcadores inmunológicos en sangre y ganglios linfáticos y en comparación con los observados en los 13 controles no vacunados. Resultados: La reducción inducida por ILIT en la respuesta de NPT observada en el primer año no se reprodujo de manera significativa en el quinto año. Las nuevas puntuaciones de CSMS fueron notablemente más bajas entre los pacientes previamente tratados que en el grupo de control. Además, aumentó la IgG4 específica frente gramíneas, disminuyó la IgE específica frente a gramíneas, se redujo la expresión del FcεR1 en los basófilos y aumentó la cantidad de células T de memoria en los ganglios linfáticos. Conclusión: La combinación de datos clínicos y parámetros inmunológicos respalda la noción de un efecto duradero de ILIT. Estos datos respaldan el concepto de ILIT como una buena alternativa a la AIT tradicional en la rinitis alérgica inducida por polen (AU)

Sensitization to Vitis vinifera Pollen in a Wine Production Area: Identification of the Allergens Involved

Background: Vine cultivation is widely distributed in La Rioja, Spain (37% of all crops) and is associated with exposure of the general population to vine pollen. The aims of this study were to investigate the prevalence of sensitization to Vitis vinifera pollen in persons with respiratory allergy in the general population and to identify the allergens involved. Materials and Methods: The study population comprised patients who came to the hospital between September 2019 and January 2020 with suspected respiratory allergy. All patients underwent skin prick testing with a panel of standardized aeroallergens, profilin, lipid transfer protein (LTP), and V vinifera pollen extract and prick-prick testing with fresh grapes. The in vitro study included specific IgE by ImmunoCap and ELISA, allergenic profile by immunoblot with individual sera from patients positive to V vinifera pollen extract, and 2D immunoblot with a pool of sera. The spots recognized by IgE were identified using mass spectrometry. Results: A total of 151 patients were included. Of these, 124 were positive to some of the allergens tested. Thirty-four (27.4%) were positive to vine pollen in the skin prick tests. The serology study revealed positive results in 20 patients. Five vine pollen allergens were identified, and profilin was the most prevalent (30%). The other 4 allergens could be considered specific to this pollen. Conclusions: Sensitization to vine pollen was frequent in the general population in a vine growing area. The clinical relevance of this finding is unknown owing to sensitization to other pollens in the vine pollen–positive patients. Five new vine pollen allergens were identified (AU)

Antecedentes: El cultivo de la vid está ampliamente distribuido en La Rioja (37% de los cultivos), lo que supone una exposición de la población general al polen de esta planta. El objetivo de este estudio fue investigar la prevalencia de sensibilización al polen de Vitis vinifera en la población general con alergia respiratoria e identificar los alérgenos implicados. Materiales y métodos: Se incluyeron en el estudio pacientes que acudieron al hospital entre septiembre de 2019 y enero de 2020 con sospecha de alergia respiratoria. A todos ellos se les realizó una prueba cutánea con el panel de aeroalérgenos estandarizados, profilina, LTP, extracto de polen de V. vinifera y Prick prick con uva. El estudio in vitro incluyó IgE específica mediante ImmunoCap y ELISA, perfil alergénico por inmunoblot con sueros individuales de pacientes positivos al extracto de polen de V. vinifera e inmunoblot 2D con un pool de sueros. Las proteínas reconocidas por la IgE fueron identificadas por espectrometría de masas. Resultados: Se incluyeron un total de 151 pacientes. De ellos, 124 fueron positivos a algunos de los alérgenos analizados. 34 (27,4%) fueron positivos a polen de vid por prueba cutánea. 20 fueron positivos tras el estudio serológico. Se identificaron 5 alérgenos del polen de la vid, siendo la profilina el más prevalente (30%). Los otros 4 alérgenos podrían considerarse específicos de este polen. Conclusión: Se detectó una alta sensibilización al polen de vid en la población general en una zona de viñedos. Se desconoce la relevancia clínica debido a la sensibilización a otros pólenes en los pacientes positivos a polen de vid. Se identificaron 5 nuevos alérgenos del polen de la vid (AU)

Granos de polen anemófilos: sensibilización en pacientes alérgicos / Anemophilic pollen grains: sensitization in allergic patients

A nivel mundial, los aeroalérgenos más frecuentes causantes de enfermedades alérgicas son los granos de polen anemófilos. Estos han sido capaces de desencadenar crisis que han reflejado una elevada morbilidad. En Cuba los estudios de sensibilización a granos de polen han sido escasos. Con el objetivo de determinar la sensibilización a granos de polen en pacientes alérgicos y su relación con la presencia de enfermedades alérgicas, se realizó un estudio observacional descriptivo de corte transversal, no aleatorizado, de marzo a junio del 2019. La muestra se constituyó de 33 pacientes con asma, rinitis, rinoconjuntivitis alérgica, dermatitis atópica y conjuntivitis alérgica. A todos los pacientes se les realizó historia clínica alergológica y prueba cutánea por punción con extractos alergénicos de: Helianthus annus, Cosmos bipinnatus, Cynodon dactylon, Quercus sp, Eucaliptus sp. Se aplicaron las frecuencias absolutas, porcientos, desviación estándar, promedio, edad media y test de Spearman para su análisis. La edad media de la muestra fue de 36,9 años, con predominio de mujeres. Más del 50por ciento de los pacientes presentaron sensibilización a granos de polen; y de ellos, el 24,24por ciento resultaron polisensibilizados. El mayor porcentaje de sensibilización fue a Cynodon dactylon. La rinitis alérgica fue la enfermedad que prevaleció en la población estudiada(AU)

Nowadays, the most frequent aeroallergens causing allergy diseases have been anemophilous pollen grains. They have been able to triggers crises that have reflected a high morbidity. In Cuba, studies of sensitization to pollen grains have been scarce. The objective of our research was to determine the sensitization to pollen grains in allergic patients and its relationship with the presence of allergic diseases. A non-randomized, descriptive, cross-sectional, observational study was conducted from March to June 2019. The sample consisted of 33 patients with asthma, allergic rhinitis, rhinoconjunctivitis, atopic dermatitis and allergic conjunctivitis. All patients underwent allergic history and skin prick test testing with allergenic extracts of: Helianthus annus, Cosmos bipinnatus, Cynodon dactylon, Quercus sp, Eucalyptus sp. Absolute frequencies, percentages, standard deviation, mean, average age, and Spearman´s test were applied for analysis. The average age of the sample was 36.9 years, with a predominance of women. More than 50percent of the patients presented sensitization to pollen grains; of them, 24.24percent polysensitized. The highest percentage of sensitization was to Cynodon dactylon. Allergic rhinitis was the disease that prevailed in the population studied(AU)

Tratamiento de la rinitis alérgica en época de pandemia. Documento de consenso de sociedades médicas de América Latina y el Caribe / Treatment of allergic rhinitis in pandemic times. Consensus statement from medical societies of Latin America and the Caribbean

La rinitis alérgica ha ido en aumento en los países latinoamericanos, dando lugar a una creciente población de pacientes que necesitan tratamiento médico para esta afección respiratoria. Su similitud con la COVID-19 en cuanto a síntomas y la posibilidad de concurrencia con esta, hacen que la rinitis alérgica sea de particular interés para los sistemas de salud. Los países de América Latina y el Caribe han sido particularmente vulnerables por múltiples desafíos, entre estos, las altas tasas de pobreza, el acceso limitado a la atención médica y las limitaciones en la prestación de servicios básicos de salud, así como la ausencia de guías de tratamiento para la rinitis alérgica en situación de pandemia. Con el objetivo de proporcionar orientación esencial para los equipos multidisciplinarios de América Latina y el Caribe con respecto a la evaluación y el tratamiento de la rinitis alérgica durante la pandemia de COVID-19, se revisó literatura científica publicada sobre tratamiento de la rinitis alérgica y COVID-19, y se consideró la opinión de profesionales líderes de sociedades científicas de la región. Se analizaron las diferentes medidas para evitar contagios, y las diferentes estrategias de tratamiento con énfasis en la terapia intranasal y el tratamiento con vacunas contra la alergia. Se formuló una declaración de posicionamiento con la intención de mantener la continuidad del servicio médico en el contexto de una pandemia y minimizar la propagación, infección y complicación asociada con el coronavirus tipo 2 del síndrome respiratorio agudo severo en pacientes con seguimiento o comenzando tratamiento para la rinitis alérgica(AU)

Allergic rhinitis has been increasing in Latin American countries, leading to a growing population of patients who need medical treatment for this respiratory condition. Its similarity to COVID-19 in terms of symptoms and the possibility of concurrence with it, make allergic rhinitis of particular interest to health systems. The countries of Latin America and the Caribbean have been particularly vulnerable due to multiple challenges, including high poverty rates, limited access to medical care and limitations in the provision of basic health services, as well as the absence of guidelines of treatment for allergic rhinitis in a pandemic situation. With the aim of to provide essential management for multidisciplinary teams in Latin America and the Caribbean regarding the evaluation and treatment of allergic rhinitis during the COVID-19 pandemic, published scientific literature on the treatment of allergic rhinitis and COVID-19 was reviewed, and the opinion of leading professionals from scientific societies in the region was considered. The different measures to avoid infections and the different treatment strategies were analyzed, with an emphasis on intranasal therapy and treatment with allergy vaccines. A position statement was formulated with the intention of maintaining continuity of medical service in the context of a pandemic and minimizing the spread, infection and complication associated with severe acute respiratory syndrome coronavirus 2 in patients undergoing or starting treatment for allergic rhinitis(AU)

House dust mite fauna characterization in the city of Rio de Janeiro and its importance in allergy diagnosis / Caracterização da fauna dos ácaros de poeira na cidade do Rio de Janeiro e sua importância em diagnósticos de alergias

Introduction: The home environment is one of the most favorable spaces for the development of mites because of its low light, humidity, and temperature. Thus, it contributes to the growing cases of allergies among atopic individuals. Objective: To investigate the faunal profile of house dust mites in the city of Rio de Janeiro and the allergenic potential in this region. Methods: Thirty dust samples were collected from homes in the city of Rio de Janeiro, and the species found were classified according to their morphology, family, and genus by classification key. For the collection region, the total protein level was assessed by the Lowry method and electrophoresis under denaturing conditions (SDSPAGE). Results: There was a predominance of Pyroglyphidae mites, accounting for 84.9% of samples; Tyrophagus putrescentiae accounted for 8%, Blomia tropicalis for 6%, Cheyletus malaccensis for 1%, and Acarus siro for 0.1%. The allergen protein content of the samples was the following: group 1 ­ 25 kDa (Der 1, Der p 1, and Blo t 1), group 2 ­ 15 kDa (Der f 2, Der 2, Tyr p 2, and Blo t 2), and group 3 ­ 29-30 kDa (Der f 3 and Blo t 3), which indicates that people in this region are susceptible to sensitization to these mites. Conclusion: Knowledge of the mite fauna in the region under study allows the guidance of health care professionals to perform skin tests for specific mites and conduct treatment according to the pool of mite extracts containing antigens, making immunotherapy more effective.

Introdução: O ambiente domiciliar é um dos espaços favoráveis para o desenvolvimento de ácaros, tendo em vista a baixa luminosidade, umidade e temperatura, o que contribui para os crescentes casos de alergias em indivíduos atópicos. Objetivo: Investigar o perfil faunístico dos ácaros na cidade do Rio de Janeiro e o potencial alergêncio para essa região. Métodos: Foram coletadas 30 amostras de poeira em residências na cidade do Rio de Janeiro, e as espécies encontradas foram classificadas quanto à morfologia, família e o gênero por chave de classificação. Para as regiões das coletas, a carga total de proteínas contendo os alérgenos foi determinada pelo método de Lowry e eletroforese em condições desnaturantes (SDS-PAGE). Resultados: Os resultados mostram a predominância de 84,9% de ácaros da família Pyroglyphidae; para os demais ácaros o percentual corresponde a 8% Tyrophagus putrescentiae, 6% Blomia tropicalis, 1% Cheyletus malaccensis, e 0,1% de Acarus siro. O conteúdo proteico alergêncio constituinte das amostras foram, grupo 1: 25 kDa (Der 1, Der p 1 e Blo t 1); grupo 2: 15 kDa (Der f 2, Der 2, Tyr p 2 e Blo t 2); e para o grupo 3: 29-30 kDa (Der f 3 e Blo t 3), o que indica uma região passível à sensibilização de indivíduos por estes ácaros. Conclusão: O conhecimento da acarofauna nas regiões em estudo permite orientar a comunidade médica quanto à realização de testes cutâneos, além da terapêutica a partir do pool de extratos de ácaros contendo os antígenos, a fim de tornar a imunoterapia mais eficaz.

Alergia a frutos do mar: principais desafios na alimentação e soluções desenvolvidas por alunos do curso de nutrição e gastronomia / Seafood allergy: main challenges in their diet and solutions developed by students of the nutrition and gastronomy course

A alergia alimentar caracteriza-se por uma reação adversa a um determinado alimento, envolvendo um mecanismo imunológico. Uma das alergias mais comuns encontradas atualmente é a alergia a frutos do mar, a qual se baseia em uma hipersensibilidade a animais desse grupo. O objetivo desta pesquisa é identificar os desafios expostos na alimentação de alérgicos a frutos do mar e formular soluções para essa população baseadas em alimentos nutricionalmente substitutos. Sendo realizado em três etapas: investigação inicial, construção de conceitos e planejamento de uma ação com orientações nutricionais. De acordo com as dificuldades encontradas na alimentação dessa parcela populacional, realizaram-se diferentes preparações, com nutrientes como ômega-3, proteínas, vitaminas do complexo B, zinco, ferro, potássio, magnésio, iodo e selênio, os quais também são encontrados nos frutos do mar, a fim de evitar possíveis contaminações cruzadas e garantir seu aporte nutricional em alimentos substitutos. Foi possível concluir que os alérgicos aos frutos do mar não apresentam uma interferência significativa em sua qualidade de vida, tendo um impacto nutricional pequeno, visto que por meio da alimentação existem outras fontes, necessitando somente de alguns cuidados no dia a dia em virtude das consequências de uma possível contaminação.

Food allergy is characterized by an adverse reaction to a given food, involving an immunological mechanism. One of the most common allergies currently found is seafood allergy, which is based on hypersensitivity to animals in this group. The objective of this research is to identify the challenges exposed in the feeding of seafood allergies and formulate solutions for this population based on nutritionally substitute foods. Being carried out in 3 stages, initial investigation, construction of concepts and planning of an action with nutritional guidance. According to the difficulties encountered in feeding this portion of the population, different preparations were carried out, with nutrients such as: ômega-3, proteins, B vitamins, zinc, iron, potassium, magnesium, iodine and selenium. Which are also found in seafood. In order to avoid possible cross-contamination and ensure their nutritional intake in substitute foods. It was possible to conclude that seafood allergies do not present a significant interference in their quality of life, having a small nutritional impact, since through food there are other sources, requiring only some care on a daily basis due to the consequences of possible contamination.

Major Allergen Content in Allergen Immunotherapy Products: The Limited Value of Numbers

The prevalence of allergic disorders has increased drastically over the last 50 years to the extent that they can be considered epidemic.At present, allergen-specific immunotherapy (AIT) is the only therapy that targets the underlying cause of allergic disorders, and evidenceof its superiority is based on data accumulated from clinical trials and observational studies demonstrating efficacy and safety. However,several aspects remain unresolved, such as harmonization and standardization of manufacturing and quantification procedures acrossmanufacturers, homogeneous reporting of strength, and the establishment of international reference standards for many allergens. Thisarticle discusses issues related to the measurement of major allergen content in AIT extracts, raising the question of whether comparison ofproducts from different manufacturers is an appropriate basis for selecting a specific AIT product. Allergen standardization in immunotherapyproducts is critical for ensuring quality and, thereby, safety and efficacy. However, lack of harmonization in manufacturing processes,allergen quantification (methodologies and references), national regulatory differences, clinical practice, and labeling shows that thecomparison of AIT products based solely on major allergen amounts is not rational and, in fact, impossible. Moreover, when rating theinformation given for a specific product, it is necessary to take into account further inherent characteristics of products and their applicationin clinical practice, such as the state of extract modification, addition of adjuvant or adjuvant system, route of administration (sublingual/subcutaneous), and cumulative dose as per posology (including the volume per administration). Finally, only convincing clinical data canserve as the basis for product-specific evaluation and cross-product comparability of individual products. (AU)

La prevalencia de las enfermedades alérgicas se ha incrementado drásticamente en los últimos 50 años y hoy pueden considerarse unaepidemia. Actualmente, la inmunoterapia específica con alérgenos (ITA) es el único tratamiento dirigido a la causa subyacente de lasenfermedades alérgicas y su superioridad se basa en resultados de ensayos clínicos/estudios observacionales que demuestran su eficaciay seguridad. Pero quedan aspectos sin resolver, como la armonización y estandarización de los procesos de fabricación y cuantificaciónentre fabricantes, la declaración homogénea de la potencia y el establecimiento de estándares internacionales de referencia. En este artículo se discuten aspectos relacionados con la medida del contenido de alérgenos mayores en los extractos de ITA, cuestionandosi, como base para elegir entre productos, es apropiada la comparación entre diferentes fabricantes. La estandarización alergénica escrucial para asegurar la calidad y, por tanto, la seguridad y eficacia de la ITA. Sin embargo, la falta de armonización en los procesos defabricación, la cuantificación alergénica, las diferencias regulatorias, la práctica clínica y el etiquetado, demuestran que comparar productosbasándose únicamente en la cantidad de alérgeno mayor no está justificado y es imposible. Además, cuando se evalúa la informaciónpara un determinado producto, deben tenerse en cuenta las características propias de cada producto y su uso clínico, como el estado dela modificación del extracto, la adición de adyuvantes, la vía de administración y la dosis acumulada. Solo datos clínicos convincentesdeben servir para la evaluación específica de cada producto o como base para la comparación entre productos. (AU)

Inmunoterapia oral con huevo en un hospital comarcal / Oral immunotherapy with egg in a regional hospital

Introducción y objetivos. La inmunoterapia oral (ITO) es una alternativa a la dieta de evitación en algunas alergias alimentarias. El objetivo de este trabajo es evaluar la eficacia y seguridad de la ITO con huevo en una consulta de alergia pediátrica. Material y métodos. Estudio observacional, longitudinal y retrospectivo de pacientes pediátricos con alergia al huevo persistente sometidos a ITO. Para la inducción se utilizó proteína de clara de huevo deshidratada administrada diariamente y con incrementos semanales hasta alcanzar una dosis de 4 gramos. Para la fase de mantenimiento se indicó una ingesta de al menos dos o tres huevos a la semana. Resultados. Se trataron 14 pacientes (6 niñas), de entre 5 y 13 años (mediana 5,5 años). Se consiguió desensibilización completa al final de la inducción en 11 pacientes (78,6%), que se mantuvo en todos ellos tras una mediana de tiempo de seguimiento de 29 meses. Durante la inducción los síntomas más frecuentes fueron: prurito orofaríngeo (9/14), dolor abdominal (7/14) y rinoconjuntivitis (6/14). Se emplearon antihistamínicos en 8 casos (57,1%) y ninguno precisó adrenalina. Entre los pacientes que consiguieron desensibilización se observó una tendencia al descenso de las IgE específicas, siendo estadísticamente significativo para las IgE a huevo completo (p = 0,047), clara de huevo (p = 0,031) y ovoalbúmina (p = 0,016). Conclusiones. La ITO con clara de huevo deshidratada resultó ser un tratamiento muy eficaz y bien tolerado en población pediátrica con alergia al huevo (AU)

Background and objective. Oral immunotherapy (OIT) is an alternative to strict avoidance for the management of some food allergies. The aim of this study is to assess the efficacy and safety of egg OIT in a paediatric allergy outpatient service. Methods. Retrospective, longitudinal observational study in children with persistent hen egg allergy who received egg OIT. For the build-up phase, dehydrated egg white was used daily. Updosing was performed weekly at the allergy unit, up to a final dose of 4 grams. Maintenance phase was carried out with a daily intake of one egg at least two or three times a week. Results. 14 patients (6 girls), whose ages ranged from 5 to 13 years (median 5.5 years) were treated with egg OIT. Eleven subject (78.6%) reached total desensitization, and all of them remained desensitized after a median follow-up time of 29 months. The most frequent adverse effects detected during the build-up phase were: oropharyngeal pruritus (9/14), abdominal pain (7/14), and rhinoconjuntivitis (6/14). Eight patients (57.1%) required oral antihistamines, and none received adrenaline. In those subjects that reached total desensitization, a trend to lower specific IgE levels was observed. That trends were statistically significand for whole egg (p = 0.047), egg white (p = 0.031), and ovalbumin (p = 0.016). Conclusions. Egg OIT was an effective and well tolerated treatment in children with egg allergY (AU)

Ácaros en sistemas de ventilación de edificios industriales: bioindicadores de la calidad del aire interior / Mites in ventilation systems of industrial buildings: bioindicators of indoors air quality

La Organización mundial de la Salud, ha señalado que 92% de la población mundial vive en lugares donde los niveles de calidad del aire se han reducido por debajo de los límites fijados, estimando que a nivel mundial aproximadamente 90% de las personas respiran aire contaminado y que la población de las ciudades pasa entre el 80 y el 90% de su tiempo en recintos cerrados, en un ambiente contaminado en mayor o menor grado; puesto que los niveles de contaminación pueden llegar a ser de 10 a 100 veces más elevados en espacios interiores respecto a los exteriores. La deficiencia en la calidad del aire interior puede dar origen a la manifestación de síntomas respiratorios relacionados como rinitis alérgica y asma, entre otras patologías y se estima que, a nivel global, millones de personas sufren de ambas enfermedades, reduciendo la calidad de vida de la población. Los ácaros constituyen los sensibilizantes respiratorios más extendidos en lugares de trabajo y están presentes en casi todos los hábitats, inclusive en el ambiente aéreo, movilizados por el viento o aerosoles, siendo la principal fuente de alérgenos interiores asociados a rinitis y asma. La presente revisión describe las características de los ácaros como fuente de contaminación ambiental y su posible utilidad como futuros bioindicadores de calidad del aire interior en sistemas de ventilación de edificios industriales con el fin de reducir la exposición y sensibilización de los trabajadores a sus alérgenos(AU)

The World Health Organization has pointed out that 92% of the world's population lives in places where air quality levels have fallen below the limits set, estimating that approximately 90% of people worldwide they breathe polluted air and that the population of cities spends between 80 and 90% of their time indoors, in an environment that is polluted to a greater or lesser degree; since pollution levels can be 10 to 100 times higher indoors than outdoors. The deficiency in indoor air quality can give rise to the manifestation of related respiratory symptoms such as allergic rhinitis and asthma, among other pathologies, and it is estimated that, globally, millions of people suffer from both diseases, reducing the quality of life of the population. mites are the most widespread respiratory sensitizers in the workplace and are present in almost all habitats, including in the air environment, moved by the wind or aerosols, being the main source of indoor allergens associated with rhinitis and asthma. This review describes the characteristics of mites as a source of environmental contamination and their possible use as future bioindicators of indoor air quality in ventilation systems of industrial buildings in order to reduce the exposure and sensitization of workers to their allergens(AU)

Labeling food allergens in the packaged food pyramid groups in Brazil: analysis of descriptions, ambiguities, and risks / Rotulagem de alérgenos alimentares em alimentos embalados segundo grupos alimentares da pirâmide brasileira: análise da descrição, riscos e ambiguidades

ABSTRACT Objective: The aim of this study was to evaluate allergenic labeling components of packaged foods for "What is the quality of food labels?" and "What is the group of Brazilian Food Pyramid that 'May contain' is predominant?." Methods: The photographs of 916 products were obtained, of which 518 were analyzed. Data from each label were evaluated according to Brazilian Food Pyramid Groups (i.e., Cereals, Fruits, & Vegetables; Soybean & products; Milk & dairy products; Meat & eggs; Fats & oils; and Sugars & sweets). Ten items were analyzed in each label, namely, the presence of a list of ingredients, alert phrase for allergy sufferers, grouping of the alert phrase, phrase location, uppercase phrase, the phrase in bold, the color of alert phrase contrasting to the background, adequate font size, do not claim the absence for any allergen with the ingredients, and others factors that make it difficult to read. For the second question, a structured questionnaire was completed, and products were classified into two categories, namely, "Contain" and "May contain." Results: The quality of the label was appropriate, and 69% of packaged foods had at least one allergen. The information "May contain" were higher in cow's milk (Cereals and Meat & eggs), soy (Soybean & products), and egg protein (Cereals). Soybean & products were the highest insecurity group. Conclusions: Brazilian health professionals can count on good-quality labeling of packaged products. Consequently, they could promote patients' and parents/caregivers' education to consult the labels and manage the risks in processed foods about precautionary allergen labeling. Soybean & products were the most significant insecurity for food choices between Brazilian Pyramid Groups.

RESUMO Objetivo: Avaliar os componentes alergênicos da rotulagem de alimentos embalados e responder "Qual é a qualidade da rotulagem?" e "Qual é o grupo de alimentos em que a expressão 'Pode conter' é predominante?". Métodos: Foram obtidas fotografias de 916 produtos, dos quais 518 foram analisados. Os dados dos rótulos foram avaliados de acordo com os grupos da pirâmide alimentar brasileira (Cereais, Frutas & Vegetais; Soja & Derivados; Leite & Laticínios; Carne & Ovos; Gorduras & Óleos; Açúcares & Doces). Dez itens foram analisados nos rótulos: presença de lista de ingredientes; frase de alerta para alérgicos; frase de alerta; local da frase; frase em letras maiúsculas; frase em negrito; a cor da frase de alerta contrastando com o fundo; tamanho de fonte adequado; não alegar ausência de qualquer alérgeno; outros fatores de difícil leitura. Para a segunda questão, foi respondido questionário estruturado, e os produtos classificados em categorias: "Contém" e "Pode conter". Resultados: A qualidade do rótulo foi adequada e 69% dos alimentos embalados continham pelo menos um alérgeno. A informação "Pode conter" foi mais identificada em: proteína do leite (Cereais e Carnes e ovos), soja (Soja & derivados) e proteína do ovo (Cereais). Soja e derivados foi o grupo alimentar de maior insegurança. Conclusões: Profissionais de saúde podem contar com rotulagem de boa qualidade dos produtos embalados e, consequentemente, promover a educação de pais/cuidadores para consultar os rótulos e gerenciar os riscos em alimentos processados. Soja e produtos são os alimentos com maior insegurança entre os Grupos da Pirâmide Brasileira.