Allergic sensitization pattern of patients in Brazil

Abstract Objective Allergic sensitization is one of the key components for the development of allergies. Polysensitization seems to be related to the persistence and severity of allergic diseases. Furthermore, allergic sensitization has a predictive role in the development of allergies. The aim of this study was to characterize the pattern of sensitization of atopic patients treated at different pediatric allergy referral centers in Brazil. Methods A nation-wide transversal multicenter study collected data on patients attended in Brazil. Peripheral blood samples were collected to determine the serum levels of allergen-specific IgE. If allergen-specific IgE was higher than 0.1 kUA/L, the following specific components were quantified. Results A total of 470 individuals were enrolled in the study. Mite sensitization was the most frequent kind in all participants. A high frequency of sensitization to furry animals and grasses featured in the respiratory allergies. Regarding components, there was a predominance of sensitization to Der p 1 and Der p 2. It has been verified that having a food allergy, atopic dermatitis, or multimorbidity are risk factors for the development of more severe allergic disease. Conclusion Studies on the pattern of allergic sensitization to a specific population offer tools for the more effectual prevention, diagnosis, and treatment of allergic diseases. Sensitization to dust mites house was the most prevalent in the evaluated sample. High rates of sensitization to furry animals also stand out. Patients with food allergy, atopic dermatitis, or multimorbidity appear to be at greater risk for developing more severe allergic diseases.

Allergic sensitization pattern of patients in Brazil.

OBJECTIVE: Allergic sensitization is one of the key components for the development of allergies. Polysensitization seems to be related to the persistence and severity of allergic diseases. Furthermore, allergic sensitization has a predictive role in the development of allergies. The aim of this study was to characterize the pattern of sensitization of atopic patients treated at different pediatric allergy referral centers in Brazil. METHODS: A nation-wide transversal multicenter study collected data on patients attended in Brazil. Peripheral blood samples were collected to determine the serum levels of allergen-specific IgE. If allergen-specific IgE was higher than 0.1 kUA/L, the following specific components were quantified. RESULTS: A total of 470 individuals were enrolled in the study. Mite sensitization was the most frequent kind in all participants. A high frequency of sensitization to furry animals and grasses featured in the respiratory allergies. Regarding components, there was a predominance of sensitization to Der p 1 and Der p 2. It has been verified that having a food allergy, atopic dermatitis, or multimorbidity are risk factors for the development of more severe allergic disease. CONCLUSION: Studies on the pattern of allergic sensitization to a specific population offer tools for the more effectual prevention, diagnosis, and treatment of allergic diseases. Sensitization to dust mites house was the most prevalent in the evaluated sample. High rates of sensitization to furry animals also stand out. Patients with food allergy, atopic dermatitis, or multimorbidity appear to be at greater risk for developing more severe allergic diseases.

Guia prático de atualização: medicamentos biológicos no tratamento da asma, doenças alérgicas e imunodeficiências / Practical update guide: biological drugs in the treatment of asthma, allergic diseases and immunodeficiencies

O presente guia apresenta revisão extensa sobre imunobiológicos utilizados, liberados e ainda sob estudo, para o tratamento da asma, doenças alérgicas e imunodeficiências. Além das características físico-químicas de alguns desses fármacos, são revisadas as indicações e os resultados de estudos clínicos realizados para avaliar eficácia e segurança. Separados por doença específica, são apresentados os principais agentes disponíveis e aprovados para utilização segundo as normas regulatórias nacionais.

This guide presents an extensive review of immunobiological drugs used, approved and/or under investigation for the treatment of asthma, allergic diseases and immunodeficiencies. In addition to the physicochemical characteristics of some of these drugs, their indications and results of clinical studies evaluating efficacy and safety are reviewed. The main agents available and approved for use in each specific disease according to national regulatory standards are presented.

Accuracy of serum IgE concentrations and papule diameter in the diagnosis of cow's milk allergy / Acurácia de concentrações de IgE séricas e de diâmetros de pápulas no diagnóstico de alergia ao leite de vaca

Abstract Objective To compare serum concentrations of specific IgE and mean papule diameters induced in the immediate skin reactivity test with cow's milk and its fractions with results of the oral challenge test, and to establish cutoff points capable of predicting clinical reactivity to cow's milk in patients treated at a referral service. Methods One hundred and twenty-two children (median of 17 months) with a history of immediate reactions to cow's milk and presence of specific IgE for cow's milk and/or its fractions (positive skin and/or IgE serum tests) were submitted to open oral challenge test with cow's milk. Results The oral challenge test was positive in 59.8% of the children, 49% of whom were males. Serum levels of specific IgE, as well as mean cow's milk papule diameters, were significantly higher in allergic patients (medians: 3.39 kUA/L vs. 1.16 kUA/L, 2.5 mm vs. 0 mm). The optimal cutoff points (Youden's index) of serum IgE specific for cow's milk and its fractions capable of predicting cow's milk reactivity (positive oral challenge test) were: 5.17 kUA/L for cow's milk, 0.95 kUA/L for α-lactalbumin, 0.82 kUA/L for β-lactoglobulin, and 0.72 kUA/L for casein, whereas for papule diameters the cutoff points were 3.5 mm for cow's milk and 6.5 mm, 9.0 mm, and 3.0 mm for the α-lactalbumin, β-lactoglobulin, and casein fractions, respectively. Conclusions The cutoff points capable of predicting clinical reactivity to cow's milk were: 5.17 kUA/L for serum-specific IgE and 3.5 mm for papule diameter measurement, values considered discriminatory for the diagnosis of cow's milk allergy.

Resumo Objetivo Comparar concentrações séricas de IgE específica e diâmetros médios das pápulas induzidas no teste cutâneo de leitura imediata com leite de vaca e suas frações com resultados do teste de provocação oral e estabelecer pontos de corte, capazes de predizer reatividade clínica ao leite de vaca em pacientes atendidos em um serviço de referência. Métodos Cento e vinte e duas crianças (mediana 17 meses), com história de reações imediatas ao leite de vaca e presença de IgE específicas para leite de vaca e/ou frações (testes cutâneos e/ou IgE sérica positivos) foram submetidas ao teste de provocação oral aberto com leite de vaca. Resultados O teste de provocação oral foi positivo em 59,8% das crianças, 49% eram do sexo masculino. Os níveis séricos de IgE específica, assim como os diâmetros médios das pápulas para leite de vaca, foram significantemente maiores nos alérgicos (medianas: 3,39kUA/L vs. 1,16 kUA/L; 2,5 mm vs. 0 mm). Os "pontos de corte ótimos" (Índice de Youden) das IgE séricas específicas para o leite de vaca e suas frações capazes de predizer a reatividade ao leite de vaca (teste de provocação oral positivo) foram: 5,17kUA/L para o leite de vaca, 0,95 kUA/L para α-lactoalbumina, 0,82kUA/L para β-lactoglobulina e 0,72kUA/L para caseína e para os diâmetros de pápulas foram 3,5 mm para leite de vaca e 6,5 mm, 9,0 mm e 3,0 mm para as frações α-lactoalbumina, β-lactoglobulina e caseína, respectivamente. Conclusões Os níveis de corte capazes de predizer reatividade clínica ao leite de vaca foram: 5,17kUA/L para IgE sérica específica e 3,5 mm para a medida do diâmetro da pápula, valores considerados discriminatórios para o diagnóstico da alergia ao leite de vaca.

Accuracy of serum IgE concentrations and papule diameter in the diagnosis of cow's milk allergy.

OBJECTIVE: To compare serum concentrations of specific IgE and mean papule diameters induced in the immediate skin reactivity test with cow's milk and its fractions with results of the oral challenge test, and to establish cutoff points capable of predicting clinical reactivity to cow's milk in patients treated at a referral service. METHODS: One hundred and twenty-two children (median of 17 months) with a history of immediate reactions to cow's milk and presence of specific IgE for cow's milk and/or its fractions (positive skin and/or IgE serum tests) were submitted to open oral challenge test with cow's milk. RESULTS: The oral challenge test was positive in 59.8% of the children, 49% of whom were males. Serum levels of specific IgE, as well as mean cow's milk papule diameters, were significantly higher in allergic patients (medians: 3.39kUA/L vs. 1.16kUA/L, 2.5mm vs. 0mm). The optimal cutoff points (Youden's index) of serum IgE specific for cow's milk and its fractions capable of predicting cow's milk reactivity (positive oral challenge test) were: 5.17kUA/L for cow's milk, 0.95kUA/L for α-lactalbumin, 0.82kUA/L for ß-lactoglobulin, and 0.72kUA/L for casein, whereas for papule diameters the cutoff points were 3.5mm for cow's milk and 6.5mm, 9.0mm, and 3.0mm for the α-lactalbumin, ß-lactoglobulin, and casein fractions, respectively. CONCLUSIONS: The cutoff points capable of predicting clinical reactivity to cow's milk were: 5.17kUA/L for serum-specific IgE and 3.5mm for papule diameter measurement, values considered discriminatory for the diagnosis of cow's milk allergy.

Vacina rotavírus: segurança e alergia alimentar ­ Posicionamento das Sociedades Brasileiras de Alergia e Imunologia (ASBAI), Imunizações (SBIm) e Pediatria (SBP) / Rotavirus vaccine: safety and food allergy ­ Position paper of the Brazilian Societies of Allergy and Immunology (ASBAI), Immunizations (SBIm), and Pediatrics (SBP)

O rotavírus continua sendo o principal agente causador de diarreia na criança, a despeito da ampla utilização de vacinas nos programas públicos de vacinação em todo o mundo. No Brasil, a vacina monovalente foi introduzida no Programa Nacional de Imunizações (PNI) em 2006, e a segurança da vacina está bem documentada em diferentes estudos pré e pós-licenciamento. Embora não haja nenhuma associação entre o uso da vacina rotavírus e o desenvolvimento da alergia às proteínas do leite de vaca (APLV), existe o receio, por parte de alguns pediatras e familiares, da vacina estar relacionada ao surgimento ou desencadeamento desta reação de hipersensibilidade. Este artigo faz uma revisão dos dados de segurança da vacina e aborda aspectos imunológicos das reações de hipersensibilidade, demonstrando não haver nexo causal entre a vacina e a APLV, reforçando o posicionamento e recomendações de organismos nacionais, internacionais e das sociedades científicas.

Despite the widespread use of vaccines in public immunization programs worldwide, rotavirus remains the primary cause of diarrhea in children. In Brazil, the monovalent vaccine was introduced in the National Immunization Program (Programa Nacional de Imunizações - PNI) in 2006, and its safety is well documented in different studies carried out both before and after licensing. Even though there is no association between the use of rotavirus vaccine and the development of cow's milk protein allergy (CMPA), some pediatricians and family members fear that the vaccine may be somehow related to the emergence or outbreak of this hypersensitivity reaction. This article reviews safety data available for this vaccine and addresses the immunological aspects of hypersensitivity reactions. The findings demonstrate that there is no causal link between the rotavirus vaccine and CMPA, reinforcing the position and recommendations of national and international agencies as well as of scientific societies.

Pediatric allergy and immunology in Brazil.

The subspecialty of pediatric allergy and immunology in Brazil is in its early years and progressing steadily. This review highlights the research developed in the past years aiming to show the characteristics of allergic and immunologic diseases in this vast country. Epidemiologic studies demonstrated the high prevalence of asthma in infants, children, and adolescents. Mortality rates and average annual variation of asthma hospitalization have reduced in all pediatric age groups. Indoor aeroallergen exposure is excessively high and contributes to the high rates of allergy sensitization. Prevalence of food allergy has increased to epidemic levels. Foods (35%), insect stings (30%), and drugs (23%) are the main etiological agents of anaphylaxis in children and adolescents. Molecular diagnosis of primary immunodeficiencies (PID) showed a high incidence of fungal infections including paracoccidioidomycosis in X-linked hyper-IgM syndrome, and the occurrence of BCG adverse reactions or other mycobacterial infections in patients with chronic granulomatous disease. Education in pediatric allergy and immunology is deficient for medical students, but residency programs are effective in training internists and pediatricians for the practice of allergy. The field of PID requires further training. Last, this review is a tribute to Prof. Dr. Charles Naspitz, one of the pioneers of our specialty in Brazil.

Milk and soy allergy.

Cow's milk allergy (CMA) affects 2% to 3% of young children and presents with a wide range of IgE and non-IgE-mediated clinical syndromes, which have a significant economic and lifestyle effect. It is logical that a review of CMA would be linked to a review of soy allergy because soy formula is often an alternative source of nutrition for infants who do not tolerate cow's milk. This review examines the epidemiology, pathogenesis, clinical features, natural history, and diagnosis of cow's milk and soy allergy. Cross-reactivity and management of milk allergy are also discussed.

Micronutrientes e sistema imunológico / Micronutrients, immunologic system and allergic diseases

Objetivo: A ingestão inadequada de alguns nutrientes pode estar associada a diferentes prejuízos na capacidade normal de defesa celular e/ou humoral, bem como na predisposição de doenças alérgicas. A presença de radicais livres parece ter papel relevante no desenvolvimento de doenças relacionadas ao sistema imunológico. Tendo em vista a elevada prevalência das deficiências de ferro, zinco e vitamina A em nosso meio, o objetivo dessa revisão foi abordar a relação entre a deficiência desses micronutrientes e o sistema imunológico. Fontes dos dados: O estudo foi realizado com base em artigos relacionados à prevenção de doenças alérgicas em crianças, disponíveis nos bancos de dados PUBMED, MEDLINE, SCIELO e LILACS nos últimos 10 anos, ou anteriores a esta data, mas relevantes do ponto de vista nutricional/epidemiológico. Síntese dos dados: A deficiência de ferro, zinco e vitamina A pode levar a diversos prejuízos na função imunológica normal, incluindo defeitos nas respostas inata e adaptativa, redução na produção de interferon-α pelos leucócitos, diminuição na linhagem precursora de células B e prejuízo na resposta de células fagocitárias, entre outros. A presença de radicais livres, traduzindo um estado de estresse oxidativo, está relacionada com o desenvolvimento de doenças alérgicas crônicas, especialmente a asma. Conclusões: A adequação nutricional de micronutrientes está intimamente relacionada ao bom funcionamento do sistema imunológico. Apesar de não haver evidências claras sobre os benefícios de uma dieta rica em antioxidantes sobre a prevenção de alergias, existem indícios de seu potencial papel protetor.

Aim: The inappropriate ingestion of some nutrients can be related to different damages on functional capacity of cellular or humoral defenses, as well as on the predisposition of allergic diseases. The presence of free radicais seems to be relevant on the development of immune system diseases. Due to the high prevalence of zinc, iron and vitamin A deficiencies in Brazil, the goal of this review is to approach the relationship between the lack of these micronutrients on immune system. Data source: The study was conducted based on related articles about prevention of allergic diseases in infants, available on PUBMED, MEDLINE, SCIELO and LILACS data bases in the last 10 years, or previous, but relevant regarding to nutritional or epidemiological point of view. Data synthesis: lron, zinc and vitamin A deficiency can lead to several damages on regular immune function, including defects on inate and adaptative responses, reduction of interferon a by leucocytes and failure on phagocytes function. Free radicals, present in oxidative stress conditions, are related to the development of chronic allergic diseases, especially asthma. Conclusion: Adequate ingestion of micronutrients is related to the good functioning of immune system. Although there are no clear evidences about benefits of a diet with high amounts of antioxidants, there are some signs of their potential protective role.

O papel da nutrição no primeiro ano de vida sobre a prevenção de doenças alérgicas / The role of nutrition in the first year of life on the prevention of allergic diseases

Objetivo: A prevalência das doenças alérgicas vem aumentando nas últimas décadas em todo o mundo. A prevenção primária em lactentes considerados de alto risco para atopias, com base na alimentação no primeiro ano de vida, pode constituir uma importante forma de atuação na tentativa se minimizar as manifestações da doença. Fontes dos dados: O estudo foi realizado com base em artigos relacionados à prevenção de doenças alérgicas em crianças, disponíveis nos bancos de dados PUBMED, MEDLINE, SCIELO e LILACS nos últimos 10 anos, ou anteriores a esta data, mas relevantes do ponto de vista nutricional/epidemiológico. Síntese dos dados: A determinação dos lactentes de alto risco para doenças alérgicas é um dado de alta relevância para a instituição de medidas nutricionais preventivas no primeiro ano de vida. Não há evidências de que a restrição dietética da mãe durante a gestação ou período de amamentação possa ter algum benefício na prevenção de atopia no feto/lactente. Aleitamento materno, diminuição da carga alergênica na substituição ou complementação do leite materno e a presença de determinados nutrientes na alimentação infantil são possíveis intervenções para se minimizar as alergias ao longo da infância. Conclusões: Aleitamento materno exclusivo por seis meses, a utilização de fórmulas hidrolisadas como complemento ou substituição do leite materno e a introdução de alimentos sólidos após o 4° mês de vida são apontadas como as possíveis estratégias na prevenção primária de doenças alérgicas, no que concerne à alimentação do primeiro ano de vida.

Aim: The prevalence of allergic diseases has been increasing in the past decades around the world. Primary prevention in high risk infants to develop allergies, based on some feeding aspects in the first year of life seems to be an important form of sction in order to minimize allergic symptoms. Data source: The study was conducted based on related articles about prevention of allergic diseases in infants, available on PUBMED, MEDLINE, SCIELO and LILACS data bases in the last 10 years, or previous, but relevant regarding to nutritional or epidemiological point of view. Data synthesis: The recognition of high risk infants for developing allergic diseases is the most relevant information for establishing preventive feeding measurements in the first year of life. There is no evidence that restriction diet during pregnancy or breastfeeding are effective for reducing atopy in the fetus/infant. Breastfeeding, decreasing intake of allergenic proteins and the presence of appropriate nutritional elements are possibly effective interventions for prevention of allergy during the infancy. Conclusion: Exclusive breastfeeding up to six months of life, hydrolyzed formula as complementation or substitution to breast milk and delayed solid food introduction after the fourth month are possibly some strategies for the primary prevention of allergic diseases, regarding to feeding in the first year of life.

Perspectivas futuras no tratamento da alergia alimentar / Future perspectives in the treatment of food allergy

Embora a restrição do alimento ao qual o paciente é sensível seja o único tratamento preconizado para as alergias alimentares, na atualidade, várias alternativas terapêuticas têm sido estudadas, sobretudo para serem administradas aos que apresentam manifestações mais graves, com risco de vida, de alergia alimentar. Entre elas destacam-se a imunomodulação realizada via imunoterapia específica com proteínas e peptídeos recombinantes, imunoestimulação por DNA, vacinas de DNA, e pelas controversas ervas medicinais chinesas. Além destas, a imunoterapia não-específica realizada com o emprego de anticorpo monoclonal anti-IgE e de anti-citocinas. Aquele impedindo a fixação da IgE ao receptor de alta presente na superfície dos mastócitos e os outros bloqueando a ação das citocinas determinantes da resposta inflamatória. Como medidas preventivas destacam-se o aleitamento materno exclusivo por tempo prolongado e os probióticos

Diferentes aspectos imunológicos da alergia alimentar / Different immunological aspects of food allergy Caso clínico comentado

Objetivo: Discutir diferentes aspectos imunológicos envolvidos no quadro de alergia alimentar de um paciente, cuja história é apresentada. Descrição: Lactente de dois anos com história de cólicas evômitos desde os primeiros meses de vida. Após a introdução dos primeiros alimentos, e principalmente do leite de vaca (LV) e soja, os sintomas foram se intensificando e modificando seu padrão e apresentou crise anafilática por duas vezes. Houve melhora dos sintomas após introdução de fórmula extensamente hidrolisada de proteína de soja. Comentários: A evolução do paciente expõe claramente diferentes mecanismos envolvidos na alergia alimentar. A história iniciou como uma típica gastroenterocolite eosinofílica alérgica, com manifestações tardias de vômitos, cólicas, irritabilidade e diminuição do ganho pôndero-estatural. O quadro evoluiu para a predominância de manifestações imediatas, envolvendo diversos órgãos e culminando em reação sistêmica grave. A fórmula de soja é tolerada na maior parte dos casos de alergia ao leite de vaca mediada por IgE, mas os hidrolisados protéicos (extensamente hidrolisados) seriam uma melhor opção para substituição do LV/soja, apesar de seu alto custo.

Mutational analysis of major, sequential IgE-binding epitopes in alpha s1-casein, a major cow's milk allergen.

BACKGROUND: Allergy to cow's milk is common in early childhood, and no therapy other than avoidance exists. In murine models of peanut allergy, immunotherapy with mutated, engineered, proteins appears promising. OBJECTIVE: We sought to identify the critical amino acids (AAs) for immunoglobulin E (IgE) binding within the major B-cell epitopes of alpha(s1)-casein, a major cow's milk allergen. This will provide the necessary information to alter the cDNA to encode a protein capable of activating milk-specific T cells, but with reduced IgE-binding capacity. METHODS: For mutational analysis of the IgE-binding epitopes, peptides of 10-14 AAs in length were synthesized on a derivatized cellulose membrane with single or multiple AA substitutions. Membranes were immunolabeled with pooled sera from 15 cow's-milk-allergic patients and with 8 individual sera. RESULTS: With the pooled sera, substitution of a single AA led to complete abrogation of IgE binding to 2 of 8 peptides and diminished binding in the remainder. Substitution of multiple AAs led to an abrogation of binding in the remaining peptides. In 4 of the 8 peptides, the critical AA identified with pooled sera did not result in significant reduction of IgE binding with 1 or more individual patients. For these patients, other critical AAs were identified, indicating a more heterogeneous pattern in IgE recognition. CONCLUSION: This study indicates that single or multiple AA substitutions within IgE-binding epitopes result in reduced binding of milk-specific IgE antibodies by patients' sera. However, for future immunotherapeutic interventions with mutated peptides, critical AAs should be evaluated with individual patient sera to determine B-cell-epitope heterogeneity.