New antihistamines: a critical view

OBJECTIVE: To perform a critical evaluation of the more recent H1 antihistamines and the various terms used to describe them, based on a review of evidence on their role in the treatment of allergic disorders. SOURCES: Original articles, reviews and consensus documents published from 1998 to 2006 and indexed in the MEDLINE and PubMed databases. Keyword: antihistamines. SUMMARY OF THE FINDINGS: Second-generation antihistamines differ from first-generation ones because of their elevated specificity and affinity for peripheral H1 receptors and because of their lower penetration of the central nervous system (CNS), having fewer sedative effects as a result. Whilst second-generation antihistamines are in general better tolerated than their predecessors, some adverse effects, principally cardiotoxicity, have been observed with some of them. Over the last 20 years, new compounds with different pharmacokinetic properties have been synthesized. The majority of these exhibit anti-inflammatory properties that are independent of their action on the H1 receptor. More recent improvements, generally in the form of active metabolites, led to the use of the term third-generation antihistamines. This term emerged spontaneously, with no clear definition of its meaning or clinical implications, creating great confusion among healthcare professionals. CONCLUSIONS: On the basis of the evidence on H1 antihistamines, none of them deserve the titlethird-generation antihistamine. As the Consensus Group on New Generation Antihistamines concluded, to merit this definition, a new class of antihistamines would have to demonstrate distinct clinical advantages over existing compounds and fulfill at least three prerequisites: they should be free from cardiotoxicity, drug interactions and effects on the CNS.OBJETIVO: Avaliar criticamente os mais novos anti-histamínicos anti-H1 e os diferentes termos utilizados para denominá-los, com base na revisão de evidências sobre o papel dos anti-H1 no tratamento das doenças alérgicas. FONTES DOS DADOS: Artigos originais, revisões e consensos indexados nos bancos de dados MEDLINE e PUBMED de 1998 a 2006. Palavra chave: anti-histamínicos. SÍNTESE DOS DADOS: Os anti-histamínicos de segunda geração diferenciam-se dos de primeira geração por sua elevada especificidade e afinidade pelos receptores H1 periféricos e pela menor penetração no sistema nervoso central (SNC), com conseqüente redução dos efeitos sedativos. Embora os anti-histamínicos de segunda geração sejam, geralmente, melhor tolerados do que seus predecessores, alguns efeitos adversos, principalmente cardiotoxicidade, surgiram com alguns deles. Nos últimos 20 anos, novos compostos, com diferentes farmacocinéticas, foram sintetizados. A maioria deles manifesta propriedades antiinflamatórias que independem de sua atividade no receptor H1. Aprimoramentos mais recentes, geralmente na forma de metabólitos ativos, levaram ao uso do termo anti-histamínico de terceira geração. Esse termo surgiu espontaneamente, sem uma descrição clara de seu significado e implicações clínicas, criando grande confusão entre os profissionais da saúde. CONCLUSÕES: Com base nas evidências sobre anti-histamínicos anti-H1, nenhum deles pode ser considerado como anti-histamínico de terceira geração. Para tanto, seria preciso comprovar que a nova classe de anti-histamínicos possui vantagens clínicas distintas sobre os compostos existentes e preenche pelo menos três pré-requisitos: ausência de cardiotoxicidade, de interações medicamentosas e de efeitos sobre o SNC.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de PediatriaUNIFESP, EPM, Depto. de PediatriaSciEL

Prevalence of symptoms of asthma, rhinitis, and atopic eczema among Brazilian children and adolescents identified by the International Study of Asthma and Allergies in Childhood (ISAAC): phase 3

OBJECTIVE: To determine the prevalence of symptoms of asthma, rhinitis, and atopic eczema among schoolchildren aged 6 to 7 years and adolescents aged 13 to 14 years in 20 Brazilian cities by using the standardized ISAAC written questionnaire, and to assess the association of this prevalence with latitude, altitude and average annual temperature of collaborating centers. METHODS: Schoolchildren and adolescents from five Brazilian regions participated in the study, totaling 23,422 ISAAC questionnaires answered by schoolchildren's parents and 58,144 questionnaires answered by adolescents. The values for latitude, altitude and average annual temperature were obtained from the Brazilian Institute of Geography and Statistics. RESULTS: The mean prevalence rates among schoolchildren and adolescents were respectively 24.3 and 19.0% for active asthma; 12.6 and 14.6% for rhinoconjunctivitis; and 8.2 and 5.0% for atopic eczema. A significant negative association was observed between latitude and physician-diagnosed asthma among schoolchildren, severe asthma, physician-diagnosed asthma, eczema and atopic eczema among adolescents. No association with altitude was found. CONCLUSIONS: The prevalence of asthma, rhinitis and atopic eczema in Brazil varies considerably. Higher prevalence rates, especially of asthma and eczema, were found at centers located closer to the equator.OBJETIVO: Determinar a prevalência de sintomas relacionados à asma, rinite e eczema atópico em escolares (EC) entre 6 e 7 anos e adolescentes (AD) entre 13 e 14 anos, residentes em 20 cidades brasileiras, empregando o questionário escrito padronizado do ISAAC, e avaliar a sua associação com a latitude, altitude e temperatura média anual dos centros de residência. MÉTODOS: Participaram do estudo EC e AD das cinco regiões do Brasil, totalizando 23.422 questionários ISAAC respondidos pelos pais de EC e 58.144 pelos próprios AD. Os índices de latitude, altitude e temperatura média anual foram obtidos do Instituto Brasileiro de Geografia e Estatística. RESULTADOS: As prevalências médias para os EC e AD, respectivamente, foram: asma ativa, 24,3 e 19,0%; rinoconjuntivite, 12,6 e 14,6%; e eczema flexural, 8,2 e 5,0%. Associação significante e negativa foi observada entre latitude e prevalência de asma diagnosticada por médico para os EC, asma grave, asma diagnosticada por médico, eczema e eczema flexural para os AD. Não houve associação com a altitude dos centros. CONCLUSÃO: A prevalência de asma, rinite e eczema atópico no Brasil foi variável. Valores mais altos, sobretudo de asma e eczema, foram observados nos centros localizados mais próximos ao Equador.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP, EPMSciEL

Fatores de risco para eczema atópico em escolares

OBJECTIVES: to study risk factors related to atopic eczema (AE) in school children of São Paulo. METHODS: 1972 parents or guardians of 6-7 years old children in the Southern Central area of São Paulo answered to a written questionnaire (standardized questionnaire of the International Study of Asthma and Allergies in Childhood plus a complementary questionnaire regarding family history of asthma and allergies, and exposure to environmental allergens). AE was defined by the presence of an itchy rash in the last year. Risk factors were analyzed through logical regression. RESULTS: the following factors were significantly associated with AE: history of maternal (OR: 4.1; 95%CI: 2.4 to 7.1) and paternal eczema (OR: 2.6; 95%CI: 1.4 to 5.0), dust in the child's bedroom (OR: 1.6; 95%CI: 1.1 to 2.4), lower maternal education (OR: 1.7; 95%CI: 1.1 to 2.7), rhinitis fever (OR: 1.7; 95%CI: 1.1 to 2.9) and wheezing in the last year (OR: 1.9; 95%CI: 1.2 to 2.8). CONCLUSIONS: our data suggest that AE has a specific pattern of inheritance. The presence of dust in the child's bedroom was the single environmental risk factor found. Diagnose of other allergic diseases, as well as the presence of recent symptoms were strongly associated with AE in children.OBJETIVOS: identificar fatores de risco relacionados ao eczema atópico (EA) em escolares do município de São Paulo. MÉTODOS: 1972 pais de escolares de 6-7 anos da região centro-sul de São Paulo responderam a questionários escritos (questionário padrão do International Study of Asthma and Allergies in Childhood e questionário complementar sobre história familiar de doenças alérgicas e exposição ambiental a potenciais fontes de alérgenos e irritantes). A presença de manchas na pele com coceira nos últimos 12 meses, definiu os escolares com EA. Os fatores de risco foram analisados por regressão logística. RESULTADOS: as variáveis significantemente associadas ao EA foram: história materna (OR: 4,1; IC95%: 2,4 a 7,1) e paterna de eczema (OR: 2,6; IC95%: 1,4 a 5,0), presença de pó no dormitório (OR: 1,6; IC95%: 1,1 a 2,4), menor escolaridade materna (OR: 1,7; IC95%: 1,1 a 2,7), relato de sibilos no último ano (OR: 1,9; IC95%: 1,2 a 2,8) e de rinite alguma vez (OR: 1,7; IC95%: 1,1 a 2,9). CONCLUSÕES: a análise dos dados sugeriu haver um padrão específico de herança genética para o EA. A presença de pó no quarto foi o único fator de risco ambiental encontrado. Sintomas e diagnóstico de outras doenças atópicas associaram-se fortemente às manifestações de EA.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Pediatrics DepartmentUNIFESP, EPM, Pediatrics DepartmentSciEL

Prevalence of atopic eczema and associated symptoms in school children

OBJECTIVE: To determine the prevalence of atopic dermatitis and associated symptoms in schoolchildren from the city of São Paulo in 1996 and 1999. METHODS: The International Study of Asthma and Allergies in Childhood (ISAAC) written questionnaire was applied to the parents of 6 to 7-year-old children in 1996 and 1999 (3,005 in 1996 and 3,033 in 1999) and to 13 to 14-year-old adolescents (3,008 in 1996 and 3,487 in 1999). In the ISAAC, the option eczema ever indicates that a diagnosis of atopic eczema was made by a physician at least once in the subject's life. This was used to define medical diagnosis in the present study. The concomitant report of lesions in the last year in characteristic places constitutes the combined criterion for the diagnosis of atopic eczema and was also employed in the present study. Data were analyzed using the Epi-Info 6.0 software. RESULTS: In the 6 to 7-year-old group, there was a significant decrease in the number of medical diagnoses of atopic eczema in 1999 (11.4%) in comparison to 1996 (13.2%). The increase in the prevalence of medical diagnoses observed in 1999 among adolescents was not significant (14 vs. 15%). Considering the combined criterion, there were no significant differences between 1996 and 1999 in either group (6.6% vs. 6.8% for 6 to 7 year-old children; 3.7% vs. 4.4% for adolescents). CONCLUSIONS: Despite the increase in the prevalence of atopic diseases worldwide, we documented a reduction in the prevalence of medical diagnoses of atopic eczema in 6 to 7-year-old children. Nevertheless, atopic eczema remains as a relevant disease in the pediatric population.OBJETIVO: Determinar a prevalência de eczema atópico e de sintomas relacionados entre estudantes da região centro-sul da cidade de São Paulo, em 1996 e 1999. MÉTODOS: Em 1996 e 1999, o questionário escrito do International Study of Asthma and Allergies in Childhood (ISAAC) foi aplicado aos pais de crianças com 6-7 anos (3.005 em 1996 e 3.033 em 1999) e a adolescentes de 13-14 anos (3.008 em 1996 e 3.487 em 1999). Para o ISAAC: a) o relato de eczema alguma vez indica que, pelo menos uma vez na vida, foi fornecido por um médico o diagnóstico de eczema atópico, sendo utilizado para definir diagnóstico médico b) o relato concomitante de lesões no último ano evidenciadas em locais característicos constitui o critério combinado para o diagnóstico de eczema atópico e foi, também, utilizado por nós. Os dados obtidos foram transcritos no banco de dados Epi-Info 6.0 e analisados. RESULTADOS: No grupo dos 6-7 anos houve redução significante do diagnóstico médico de eczema atópico em 1999 (11,4%) em comparação a 1996 (13,2%). O aumento da prevalência de diagnóstico médico observado em 1999, entre os adolescentes, não foi significante (14% x 15%). Considerando-se o critério combinado, não houve diferenças significantes, entre 1996 e 1999, em ambos os grupos (6,6% x 6,8% para crianças de 6-7 anos e 3,7% x 4,4% para adolescentes). CONCLUSÕES: Apesar do aumento da prevalência das doenças atópicas em várias partes do mundo, documentamos redução na prevalência de diagnóstico médico de eczema atópico entre crianças de 6 a 7 anos. Contudo, o eczema atópico é doença relevante na população pediátrica.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de PediatriaUNIFESP, EPM, Depto. de PediatriaSciEL

Is allergic rhinitis a trivial disease?

BACKGROUND: Asthma and rhinitis often coexist, which potentially increases the disease severity and can negatively impact a patients' quality of life. However, there are few reports based on data obtained from the International Study of Asthma and Allergies in Childhood examining asthma severity in combination with rhinitisrelated symptoms. OBJECTIVE: To demonstrate whether current rhinitis and current rhinoconjunctivitis are associated with the development of asthma or its increasing severity in Brazilian adolescents. METHODS: The prevalence of current asthma was correlated with the prevalence of current rhinitis and current rhinoconjunctivitis in adolescents (13 to 14 year olds) from 16 Brazilian centers (based on Spearman's rank correlation index). The influence of current rhinitis and current rhinoconjunctivitis on asthma presentation was also evaluated using the chi-squared test and was expressed as odds ratios with 95% confidence intervals (95%CI). RESULTS: A significant positive correlation was observed between the prevalence of current asthma and current rhinitis (rs = 0.82; 95%CI: 0.60-0.93, p< 0.0001) and between the prevalence of current asthma and current rhinoconjunctivitis (rs = 0.75; 95%CI: 0.47-0.89, p < 0.0001). Current rhinitis was associated with a significantly increased risk of current asthma and of more severe asthma. Similar results were observed for current rhinoconjunctivitis. CONCLUSION: In this epidemiologic study of Brazilian adolescents, the presence of current rhinitis and current rhinoconjunctivitis was associated with a high risk of developing asthma and increased asthma severity. The mutual evaluation of rhinitis and asthma is necessary to establish an adequate treatment plan

Drug hypersensitivity in students from São Paulo, Brazil

BACKGROUND: Drug hypersensitivity is responsible for substantial mortality and morbidity, and increased health costs. However, epidemiological data on drug hypersensitivity in general or specific populations are scarce. METHODS: We performed a cross-sectional survey of 1015 university students, using a self-reported questionnaire. RESULTS: The prevalence of self-reported drug hypersensitivity was 12,11% (123/1015). The most frequently implicated drugs were non-steroidal anti-inflammatory drugs (45,9%) and beta-lactam and sulfonamide antibiotics (25,40%). The majority of the patients reported dermatological manifestations (99), followed by respiratory (40), digestive (23) and other (19). Forty-five patients had an immediate type reaction, and 76,72% (89) had the drug by oral route. CONCLUSION: The results showed that drug hypersensitivity is highly prevalent in university students, and that nonsteroidal anti-inflammatory drug and antibiotics (beta-lactams and sulfonamide) are the most frequently concerned drugs

Laboratorial approach in the diagnosis of food allergy

OBJCTIVE: Review the available laboratory tests used to assist in the diagnosis of IgE-mediated and non-IgE-mediated food allergy. DATA SOURCES: Papers in English and Portuguese published in PubMed and Embase, in the last ten years. Terms searched were food allergy, diagnose and laboratory, isolated and/or associated. DATA SYNTHESIS: The diagnostic approach to food allergy reactions includes a good medical history, laboratory studies, elimination diets and blinded food challenges. More recently, the use of a quantitative measurement of food-specific IgE antibodies has been shown to be more predictive of symptomatic IgE-mediated food allergy. Food-specific IgE serum levels exceeding the diagnostic values indicate that the patient is greater than 95% likely to experience an allergic reaction if he/she ingests the specific food. Such decision point values have been defined just for some foods and inconsistent results were obtained when allergy to the same food was studied in different centers. Food challenges, in particular the double-blind placebo-controlled food challenge (DBPCFC), represent the most reliable way to establish or rule out food hypersensitivity. CONCLUSIONS: A number of recent developments are improving the predictive value of some laboratory tests for the diagnosis of food allergies. However, to date, no in-vitro or in-vivo test shows full correlation with clinical food allergy and the DBPCFC remains the gold standard for the definitive diagnosis of specific food allergies. There is an urgent need for new and fundamentally improved diagnostic approaches, which must be validated in patients with food allergy confirmed by a positive DBPCFC.OBJETIVO: Revisar os exames laboratoriais disponíveis utilizados no diagnóstico da alergia alimentar mediada ou não por IgE. FONTES DE DADOS: Artigos publicados em base de dados PubMed e Embase (língua inglesa e portuguesa) nos últimos dez anos. As palavras-chave utilizadas como fonte de busca foram alergia alimentar, diagnóstico e laboratório, isolados e/ou associados. SÍNTESE DOS DADOS: A abordagem diagnóstica das reações alérgicas a alimentos inclui história clínica completa, estudos laboratoriais, dietas de eliminação e desencadeamentos cegos com alimentos. Recentemente, a medida quantitativa de anticorpos IgE específicos a alimentos tem mostrado ser mais preditiva de alergia alimentar sintomática mediada por IgE. Níveis séricos de IgE específica a alimento que excedam os valores diagnósticos indicam que o paciente tem chance maior que 95% de apresentar uma reação alérgica se ingerir o alimento em questão. Estes valores de decisão foram definidos para alguns alimentos e resultados inconsistentes são obtidos ao se estudar diferentes populações. Os desencadeamentos com alimento, especialmente o duplo-cego controlado por placebo (DADCCP), representa a maneira mais confiável de estabelecer ou descartar o diagnóstico de hipersensibilidade alimentar. CONCLUSÕES: Número crescente de aquisições tem melhorado o valor preditivo de alguns testes laboratoriais empregados no diagnóstico de alergias alimentares. Entretanto, até hoje, não há teste in vitro ou in vivo que mostre correlação completa com a clínica da alergia alimentar. O DADCCP continua sendo o padrão-ouro no diagnóstico definitivo de alergia alimentar específica. São necessárias, urgentemente, novas abordagens diagnósticas válidadas em pacientes com alergia alimentar confirmada por DADCCP positivo.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de PediatriaUNIFESP-EPM Departamento de PediatriaUniversidade de São Paulo Faculdade de Medicina Departamento de PediatriaUniversidade Federal da Bahia Departamento de PediatriaUNIFESP-EPMUniversidade Federal do Paraná Departamento de PediatriaUNIFESP, EPM, Depto. de PediatriaUNIFESP, EPM Depto. de PediatriaUNIFESP, EPMSciEL