Atualização em reações de hipersensibilidade aos anti-inflamatórios não esteroidais ­ Parte 2: manifestações clínicas, fenótipos, diagnóstico e manejo / Update on hypersensitivity reactions to nonsteroidal anti-inflammatory drugs ­ Part 2: clinical features, phenotypes, diagnosis, and management

Os anti-inflamatórios não esteroidais (AINE) são os fármacos mais frequentemente associados a reações de hipersensibilidade (RH) na prática clínica. Na parte 2 dessa atualização sobre as RH aos AINE, discutiremos os aspectos clínicos dessas reações, com foco nos sinais e sintomas, como diferenciar os fenótipos clínicos, fazer a orientação desses pacientes e quando indicar procedimentos complementares, como testes cutâneos, de provocação e dessensibilização.

Nonsteroidal anti-inflammatory drugs are a major cause of drug hypersensitivity reactions in clinical practice. In this "Update Part 2", we discuss the clinical picture, including the main signs and symptoms, how to distinguish clinical phenotypes, how to manage affected patients, and when to indicate additional procedures, such as skin testing, challenge, and desensitization.

Atualização em reações de hipersensibilidade aos anti-inflamatórios não esteroidais ­ Parte 1: definições, farmacologia, epidemiologia, fisiopatologia e fatores genéticos / Update on hypersensitivity reactions to nonsteroidal anti-inflammatory drugs ­ Part 1: definitions, pharmacology, epidemiology, pathophysiology, and genetics

Os anti-inflamatórios não esteroidais (AINE) estão entre os medicamentos mais utilizados no mundo e são os fármacos mais frequentemente associados à ocorrência de reações de hipersensibilidade na América Latina. As reações têm grande variabilidade de apresentações clínicas e, consequentemente, com abordagem terapêutica difícil. Nesta revisão, abordamos aspectos farmacológicos dos AINE, bem como as definições, epidemiologia e fisiopatologia das reações de hipersensibilidade aos AINE. Por fim, discutimos aspectos genéticos associados à intolerância e alergia a esses fármacos.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used medications worldwide and the drugs most frequently associated with the occurrence of hypersensitivity reactions in Latin America. The clinical presentation of the reactions varies widely, which makes them difficult to treat. In this review, we address pharmacological aspects of NSAIDs, as well as the definitions, epidemiology, and pathophysiology of hypersensitivity reactions to NSAIDs. Finally, we discuss genetic factors associated with intolerance and allergy to these drugs.

Atualização em reações de hipersensibilidade aos anestésicos locais / Update on local anesthetics hypersensitivity reactions

Os anestésicos locais são essenciais em diversos procedimentos médicos e odontológicos. Funcionam estabilizando as membranas neuronais e inibindo a transmissão de impulsos neurais, o que permite a realização desses procedimentos com mais segurança e sem dor. As reações adversas a drogas são definidas pela Organização Mundial da Saúde como todos os efeitos nocivos, não intencionais e indesejáveis de uma medicação, que ocorrem em doses usadas para prevenção, diagnóstico e tratamento. As reações de hipersensibilidade são reações adversas do tipo B, imprevisíveis, que clinicamente se assemelham a reações alérgicas e podem ou não envolver um mecanismo imune. As reações de hipersensibilidade verdadeiras aos anestésicos locais são raras, apesar de superestimadas. Nesta revisão destacamos a necessidade de uma avaliação completa dos pacientes com suspeita de reação alérgica aos anestésicos locais, incluindo a investigação de outros possíveis alérgenos que tenham sido utilizados no procedimento, como analgésicos, antibióticos e látex. A estratégia de investigação e seleção de pacientes para testes deve se basear na história clínica. Dessa forma, poderemos fornecer orientações mais assertivas e seguras aos pacientes.

Local anesthetics are essential in many medical and dental procedures. They work by stabilizing neuronal membranes and inhibiting the transmission of neural impulses, which allows these procedures to be performed more safely and without pain. Adverse drug reactions are defined by the World Health Organization as all harmful, unintended and undesirable effects of a medication, which occur at doses used for prevention, diagnosis and treatment. Hypersensitivity reactions are unpredictable type B adverse reactions that clinically resemble allergic reactions and may or may not involve an immune mechanism. True hypersensitivity reactions to local anesthetics are rare, although overestimated. In this review, we highlight the need for a thorough evaluation of patients with suspected allergic reaction to local anesthetics, including investigation of other possible allergens that may have been used in the procedure, such as analgesics, antibiotics and latex. The investigation strategy and patient selection for testing should be based on clinical history. In this way, we will be able to provide more assertive and safe guidelines to patients.

Reatividade cruzada entre betalactâmicos: uma abordagem prática / Cross-reactivity among beta-lactams: a practical approach

Os betalactâmicos são a classe de drogas que mais causam reações de hipersensibilidade envolvendo um mecanismo imunológico específico, e são os principais desencadeantes entre os antimicrobianos. São representados pelas penicilinas, cefalosporinas, carbapenêmicos, monobactâmicos e inibidores da betalactamase. A estrutura química básica destes fármacos consiste na presença dos seguintes componentes: anel betalactâmico, anel adjacente e cadeias laterais, sendo todos potenciais epítopos. Os anticorpos da classe IgE e linfócitos T estão frequentemente envolvidos no reconhecimento desses epítopos. A reatividade cruzada depende da estabilidade dos produtos intermediários (determinantes antigênicos) derivados da degradação dos anéis betalactâmicos, anéis adicionais e da semelhança estrutural das cadeias laterais entre as drogas. Classicamente acreditava-se num grande potencial de reatividade cruzada dentro de cada classe e até entre as classes, mas estudos da última década mostraram que indivíduos alérgicos à penicilina (com testes cutâneos positivos) reagiam às cefalosporinas em aproximadamente 3% dos casos, aos carbapenêmicos em cerca de 1%, e praticamente não reagiam aos monobactâmicos. Essa reatividade ou tolerância parece estar vinculada ao grau de similaridade entre as cadeias laterais desses antibióticos. Nesta revisão, ressaltamos a importância da investigação sistematizada na confirmação ou exclusão de alergia aos betalactâmicos, descrevemos a prevalência da reatividade cruzada entre estes fármacos e sugerimos um algoritmo de abordagem desses pacientes baseados em sua estrutura química e nos dados publicados na literatura.

Beta-lactams are the drugs most commonly involved in hypersensitivity reactions mediated by a specific immune mechanism and are the main triggers among antibiotics. They include penicillins, cephalosporins, carbapenems, monobactams and beta-lactam inhibitors. The basic chemical structure of these drugs consist on the presence of the following components: betalactam ring, an adjacent ring and side chains, all of which are potential epitopes. IgE antibodies and T lymphocytes are often involved in recognizing those epitopes. Cross-reactivity depends on the stability of intermediate products (antigenic determinants) derived from the degradation of the beta-lactam ring, on the adjacent rings, and on the structural similarity of the side chains between drugs. Classically, it was believed that there was a great potential for cross-reactivity within each class and even between classes, but studies from the last decade showed that individuals allergic to penicillin (with positive skin tests) reacted to cephalosporins in approximately 3% of cases, to carbapenems in about 1%, and rarely reacted to monobactams. This reactivity or tolerance seems to be linked to the degree of similarity between the side chains of these antibiotics. In this review, we emphasize the importance of systematic investigation to confirm or exclude allergy to beta-lactams, we describe the prevalence of crossreactivity between these drugs and we suggest an algorithm for approaching these patients based on their chemical structure and on data published in the literature.

Allergy to penicillin and betalactam antibiotics.

Betalactams are the most frequent cause of hypersensitivity reactions to drugs mediated by a specific immune mechanism. Immediate reactions occur within 1 to 6 hours after betalactam administration, and are generally IgE-mediated. They clinically translate into urticaria, angioedema and anaphylaxis. Non-immediate or delayed reactions occur after 1 hour of administration. These are the most common reactions and are usually mediated by T cells. The most frequent type is the maculopapular or morbilliform exanthematous eruption. Most individuals who report allergies to penicillin and betalactams can tolerate this group of antibiotics. To make diagnosis, a detailed medical history is essential to verify whether it was an immediate or non-immediate reaction. Thereafter, in vivo and/or in vitro tests for investigation may be performed. The challenging test is considered the gold standard method for diagnosis of betalactam hypersensitivity. The first approach when suspecting a reaction to betalactam is to discontinue exposure to the drug, and the only specific treatment is desensitization, which has very precise indications. The misdiagnosis of penicillin allergy affects the health system, since the "penicillin allergy" label is associated with increased bacterial resistance, higher rate of therapeutic failure, prolonged hospitalizations, readmissions, and increased costs. Thus, it is essential to develop strategies to assist the prescription of antibiotics in patients identified with a label of "betalactam allergy" at hospitals, and to enhance education of patients and their caregivers, as well as of non-specialist physicians.

Allergy to penicillin and betalactam antibiotics / Alergia a penicilina e antibióticos beta-lactâmicos

ABSTRACT Betalactams are the most frequent cause of hypersensitivity reactions to drugs mediated by a specific immune mechanism. Immediate reactions occur within 1 to 6 hours after betalactam administration, and are generally IgE-mediated. They clinically translate into urticaria, angioedema and anaphylaxis. Non-immediate or delayed reactions occur after 1 hour of administration. These are the most common reactions and are usually mediated by T cells. The most frequent type is the maculopapular or morbilliform exanthematous eruption. Most individuals who report allergies to penicillin and betalactams can tolerate this group of antibiotics. To make diagnosis, a detailed medical history is essential to verify whether it was an immediate or non-immediate reaction. Thereafter, in vivo and/or in vitro tests for investigation may be performed. The challenging test is considered the gold standard method for diagnosis of betalactam hypersensitivity. The first approach when suspecting a reaction to betalactam is to discontinue exposure to the drug, and the only specific treatment is desensitization, which has very precise indications. The misdiagnosis of penicillin allergy affects the health system, since the "penicillin allergy" label is associated with increased bacterial resistance, higher rate of therapeutic failure, prolonged hospitalizations, readmissions, and increased costs. Thus, it is essential to develop strategies to assist the prescription of antibiotics in patients identified with a label of "betalactam allergy" at hospitals, and to enhance education of patients and their caregivers, as well as of non-specialist physicians.

RESUMO Os beta-lactâmicos constituem a causa mais frequente de reações de hipersensibilidade a fármacos mediadas por mecanismo imunológico específico. As reações imediatas ocorrem em 1 até 6 horas após a administração do beta-lactâmico, sendo geralmente IgE-mediadas. Elas se traduzem clinicamente por urticária, angioedema e anafilaxia. As reações não imediatas ou tardias ocorrem após 1 hora da administração. São as reações mais comuns, sendo geralmente mediadas por células T. O tipo mais frequente é o exantema maculopapular ou morbiliforme. A maioria dos indivíduos que refere alergia aos beta-lactâmicos pode tolerar esse grupo de antibióticos. No diagnóstico, uma história clínica detalhada é fundamental para verificar se a reação foi do tipo imediato ou não imediato. A partir daí, podem ser realizados testes in vivo e/ou in vitro para investigação. O teste de provocação é considerado o método padrão-ouro no diagnóstico de hipersensibilidade aos beta-lactâmicos. A primeira conduta diante da suspeita de uma reação ao beta-lactâmico é suspender a exposição ao medicamento, e o único tratamento específico é a dessensibilização, que possui indicações bem precisas. O diagnóstico equivocado de alergia à penicilina afeta o sistema de saúde, pois o rótulo de "alergia à penicilina" está associado a aumento da resistência bacteriana, maior índice de falha terapêutica, hospitalizações prolongadas, readmissões e aumento dos custos. Assim, torna-se fundamental elaborar estratégias com o objetivo de auxiliar na prescrição de antibióticos em pacientes com rótulo de "alergia aos beta-lactâmicos" nos hospitais e melhorar a educação dos pacientes e seus responsáveis, além de médicos não especialistas.

Anafilaxia: dados de um registro de pacientes atendidos em um serviço especializado / Anaphylaxis: data from a patient registry in a specialized service

Introdução: Dados relacionados à prevalência e incidência da anafilaxia são escassos, especialmente no Brasil. Objetivo: Descrever o perfil epidemiológico e características das reações em pacientes com diagnóstico de anafilaxia assistidos em um ambulatório especializado de alergia. Métodos: Análise de um registro de pacientes (maio/2017 a junho/2018) com diagnóstico de anafilaxia. Informações sobre idade, sexo, apresentação clínica, desencadeantes, conhecimento prévio do desencadeante, estudos diagnósticos realizados, antecedentes pessoais de atopia, tempo entre a exposição e a reação, ambiente onde ocorreu a reação, tratamento e gravidade foram analisados. Resultados: Do total de 150 pacientes (43 dias de vida a 67 anos), 52% eram homens e 66% tinham menos de 18 anos. As principais manifestações clínicas referidas foram as cutâneas e as respiratórias. O tempo entre a exposição ao desencadeante e a reação foi mais comumente menor de 10 minutos. A maioria dos pacientes teve anafilaxia em ambiente não hospitalar, porém, 78% foram tratados em ambiente hospitalar e 57% destes receberam adrenalina intramuscular (IM). Os desencadeantes foram confirmados em 78% dos casos, e os alimentos e as drogas foram os mais implicados. Os pacientes que apresentaram reações desencadeadas por alimentos eram mais jovens e relatavam mais frequentemente reações em menos de 10 minutos e em ambiente não hospitalar. Estes pacientes também relatavam mais frequentemente que conheciam previamente o desencadeante, apresentam antecedente pessoal de atopia e receberam tratamento com adrenalina intramuscular (IM). Dezesseis pacientes apresentaram reações graves, sendo mais frequentes nas mulheres e nos maiores de 18 anos. Conclusão: A anafilaxia por drogas ou por alimentos manifesta diferenças clínicas quanto à idade, ter antecedentes de atopia, local da reação e tempo para início da reação. A gravidade das reações anafiláticas associou-se à idade dos pacientes.

Introduction: Data on prevalence and incidence of anaphylaxis are scarce, especially in Brazil. Objective: To describe the epidemiological profile and characteristics of reactions in patients diagnosed with anaphylaxis seen at an allergy outpatient clinic. Methods: A patient registry of confirmed cases of anaphylaxis (from May 2017 to June 2018) was analyzed. Age, gender, clinical presentation, triggers, previous knowledge of the trigger, diagnostic studies, atopy background, time gap between exposure and reaction, place where the reaction occurred, treatment and severity were analyzed. Results: From a total of 150 patients (43 days to 67 years of age), 52% were men and 66% were under 18 years of age. The most frequent symptom categories were cutaneous and respiratory. The time gap between exposure to trigger and reaction was more commonly less than 10 minutes. Most of the patients had anaphylaxis in a non-hospital setting; however, 78% were treated in a hospital and 57% of them received intramuscular (IM) epinephrine. The triggers were identified in 78% of cases and predominantly consisted of food and drugs. Patients who had a food-triggered reaction were younger and more frequently reported reactions in less than 10 minutes and in non-hospital settings. These patients also more frequently reported previous knowledge of the trigger, had an atopy background and were treated with IM epinephrine. Sixteen patients had severe reactions, which were more frequent in women and in those over 18 years of age. Conclusion: Clinical manifestations of anaphylaxis triggered by drugs or food may vary depending on age, atopy background, place where the reaction occurs, and time gap before initiation of the reaction. The severity of anaphylactic reactions was associated with age of the patients.

Testes in vivo nas reações de hipersensibilidade a medicamentos - Parte II: testes de provocação / In vivo tests in hypersensitivity drug reactions - Part II: provocation tests

O diagnóstico das reações de hipersensibilidade a medicamentos é baseado na história clínica, seguida pela realização de testes in vivo, que podem ser cutâneos ou de provocação. Os testes de provocação são considerados o padrão-ouro no diagnóstico, sendo importantes tanto para a confirmação diagnóstica como para o encontro de opções terapêuticas seguras. Recentemente, assim como os testes cutâneos, as provocações com medicamentos foram aprovadas pela Câmara Técnica da Associação Médica Brasileira para uso no diagnóstico das reações a drogas. Nesta revisão, nosso foco serão as indicações, contraindicações e método dos testes de provocação com medicamentos.

Diagnosis of hypersensitivity drug reactions is based on clinical history, followed by in vivo tests, such as skin tests and drug provocation tests. Drug provocation tests are considered the gold standard for diagnosis. They are important both for confirming diagnosis and for finding safe therapeutic options. As for skin tests, provocation tests were recently approved by the Brazilian Medical Association Technical Board to be used in hypersensitivity drug diagnosis. In this review paper, we will focus on indications, contraindications and method of drug provocation tests.

Testes in vivo nas reações de hipersensibilidade a medicamentos - Parte I: testes cutâneos / In vivo tests in hypersensitivity drug reactions - Part I: skin tests

As reações de hipersensibilidade a medicamentos são frequentes na prática clínica e são consideradas problema de saúde pública. O diagnóstico inclui, após detalhada história clínica, a realização de testes in vivo: cutâneos ou de provocação. Recentemente, estes testes foram aprovados pela Câmara Técnica da Associação Médica Brasileira para inclusão tanto no SUS, como na Saúde Suplementar, o que facilitará o acesso dos pacientes a estas ferramentas. Nesta revisão, abordaremos com mais detalhes as indicações, técnica e impacto da utilização dos testes cutâneos com fármacos na prática clínica.

Hypersensitivity drug reactions are frequent in clinical practice and are considered an important public health issue. Diagnosis includes a detailed clinical history, followed by in vivo tests, such as skin tests and drug provocation tests. Those tests were recently approved by the Brazilian Medical Association Technical Board to be included in both public and private practice, which will facilitate investigation with those tools. In this review paper, we will address in more detail the indications, technique, and impact of the use of skin tests to drugs in clinical practice.

Hipersensibilidade a anti-inflamatórios não esteroidais em crianças: relato de dois casos e revisão das novas classificações / Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs in children: report of two cases and review of new classifications

Os anti-inflamatórios não esteroidais (AINEs) são amplamente utilizados para tratamento de dor e/ou febre em crianças. Atualmente, constituem a principal causa de reação de hipersensibilidade (RH) a medicamentos em adultos e crianças de vários países, inclusive do Brasil. Existem dois mecanismos envolvidos nessas reações: mecanismos não imunológicos (devido à inibição da enzima ciclooxigenase), e mecanismos imunológicos responsáveis pelas reações alérgicas (mediadas por IgE ou células T). As reações mais comuns em crianças e adolescentes são aquelas decorrentes de mecanismos não imunológicos. As manifestações clínicas variam desde urticária/angioedema/anafilaxia, que ocorrem em poucos minutos a horas após a administração do AINE, até reações tardias, que podem surgir vários dias após o início do tratamento. A história clínica detalhada é fundamental para o diagnóstico. Os testes in vitro são pouco validados, mas os testes cutâneos podem ser realizados nos casos de suspeita de uma RH seletiva, com provável mecanismo imunológico. O teste de provocação oral (TPO) é considerado o padrão ouro para o diagnóstico, e pode auxiliar na escolha de uma alternativa segura. Este artigo relata dois casos de hipersensibilidade a AINEs em crianças que ilustram tipos diferentes de mecanismos (não imunológico e imunológico) com manifestações clínicas distintas: urticária (imediata) e erupção fixa por droga (não imediata). Existe dificuldade na classificação das RHs aos AINEs, assim como ocorreu em um dos casos descritos. Portanto, há necessidade de mais estudos nessa área buscando ampliar o conhecimento e melhorar a avaliação e seguimento dessas crianças com RH a AINEs.

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat pain and fever in children. Currently, they are considered the main cause of drug hypersensitivity reaction (DHR) in adults and children from several countries, including Brazil. There are two mechanisms involved in these reactions: non-immune (due to inhibition of cyclooxygenase enzyme) and immune mechanisms responsible for allergic reactions (IgE or T-cell mediated). The most common reactions in children and adolescents are those resulting from non-immunological mechanisms. Clinical manifestations range from urticaria/angioedema/anaphylaxis that occur within a few minutes to hours after NSAID administration up to late reactions that may occur several days after starting treatment. Detailed medical history is critical to diagnosis. In vitro tests are poorly validated, but skin tests can be performed in cases of suspected selective DHR with a probable immune mechanism. Oral provocation test (OPT) is considered the "gold standard" for diagnosis and may help in choosing a safe alternative. This article reports two cases of hypersensitivity to NSAIDs in children that illustrate different types of mechanisms (non-immunological and immunological) with distinct clinical manifestations: urticaria (immediate) and fixed drug eruption (non-immediate). There is difficulty in classifying DHRs for NSAIDs, as occurred in one of the cases described. Therefore, there is a need for further studies in this area in order to increase knowledge and improve the evaluation and follow-up of these children with DHR to NSAIDs.

Asthma in children and adolescents in Brazil: contribution of the International Study of Asthma and Allergies in Childhood (ISAAC).

OBJECTIVE: To assess asthma among Brazilian pediatric population applying the International Study of Asthma and Allergies in Childhood (ISAAC), an internationally standardized and validated protocol. DATA SOURCES: ISAAC was conceived to maximize the value of epidemiologic studies on asthma and allergic diseases, establishing a standardized method (self-applicable written questionnaire and/or video questionnaire) capable to facilitate the international collaboration. Designed to be carried out in three successive and dependent phases, the ISAAC gathered a casuistic hitherto unimaginable in the world and in Brazil. This review included data gathered from ISAAC official Brazilian centers and others who used this method. DATA SYNTHESIS: At the end of the first phase, it has been documented that the prevalence of asthma among Brazilian schoolchildren was the eighth among all centers participating all over the world. Few centers participated in the second phase and investigated possible etiological factors, especially those suggested by the first phase, and brought forth many conjectures. The third phase, repeated seven years later, assessed the evolutionary trend of asthma and allergic diseases prevalence in centers that participated simultaneously in phases I and III and in other centers not involved in phase I. CONCLUSIONS: In Brazil, the ISAAC study showed that asthma is a disease of high prevalence and impact in children and adolescents and should be seen as a Public Health problem. Important regional variations, not well understood yet, and several risk factors were found, which makes us wonder: is there only one or many asthmas in Brazil?

Asthma in children and adolescents in Brazil: contribution of the International Study of Asthma and Allergies in Childhood (ISAAC) / Asma en el nino y en el adolescente brasilenos: aporte del International Study of Asthma and Allergies in Childhood (ISAAC) / A asma na criança e no adolescente brasileiro: contribuição do International Study of Asthma and Allergies in Childhood (ISAAC)

Objective: To assess asthma among Brazilian pediatric population applying the International Study of Asthma and Allergies in Childhood (ISAAC), an internationally standardized and validated protocol. Data sources: ISAAC was conceived to maximize the value of epidemiologic studies on asthma and allergic diseases, establishing a standardized method (self-applicable written questionnaire and/or video questionnaire) capable to facilitate the international collaboration. Designed to be carried out in three successive and dependent phases, the ISAAC gathered a casuistic hitherto unimaginable in the world and in Brazil. This review included data gathered from ISAAC official Brazilian centers and others who used this method. Data synthesis: At the end of the first phase, it has been documented that the prevalence of asthma among Brazilian schoolchildren was the eighth among all centers participating all over the world. Few centers participated in the second phase and investigated possible etiological factors, especially those suggested by the first phase, and brought forth many conjectures. The third phase, repeated seven years later, assessed the evolutionary trend of asthma and allergic diseases prevalence in centers that participated simultaneously in phases I and III and in other centers not involved in phase I. Conclusions: In Brazil, the ISAAC study showed that asthma is a disease of high prevalence and impact in children and adolescents and should be seen as a Public Health problem. Important regional variations, not well understood yet, and several risk factors were found, which makes us wonder: is there only one or many asthmas in Brazil? .

Objetivo: Evaluar el asma en la población pediátrica brasileña por el protocolo del International Study of Asthma and Allergies in Childhood (ISAAC), internacionalmente estandarizado y validado. Fuentes de datos : El ISAAC, idealizado para maximizar el valor de estudios epidemiológicos en asma y enfermedades alérgicas, estableció un método estandarizado (cuestionario escrito autoaplicable y/o video-cuestionario) capaz de facilitar la colaboración internacional. Concebido para realizarse en tres etapas sucesivas y dependientes, el ISAAC reunió una casuística hasta entonces inimaginable en el mundo y en Brasil. En esta visión, se reunieron los datos de centros brasileños oficiales del ISAAC y de otros que emplean su método. Síntesis de los datos: Finalizada la primera etapa, la prevalencia de asma entre escolares brasileños fue documentada como la octava en magnitud entre todos los centros participantes del estudio. Los pocos centros involucrados en la segunda etapa investigaron posibles factores etiológicos, especialmente aquellos sugeridos por los resultados de la primera etapa, y generaron muchas especulaciones. La tercera etapa, repetida tras siete años, evaluó la tendencia evolutiva de la prevalencia de asma y de las enfermedades alérgicas en los centros participantes simultáneamente en las etapas I y III y determinó la prevalencia en otros no involucrados en la etapa I. Conclusiones: En Brasil, el ISAAC demostró, de modo definitivo, que el asma es una enfermedad de alta prevalencia e impacto en niños y adolescentes, debiendo ser encarada como problema de Salud Pública. Se encontraron importantes variaciones regionales, todavía no bien aclaradas, así como diversos factores de riesgo, lo que nos hace cuestionar: ¿hay en Brasil una o muchas asmas? .

Objetivo: Avaliar a asma na população pediátrica brasileira pelo protocolo do International Study of Asthma and Allergies in Childhood (ISAAC), internacionalmente padronizado e validado. Fontes de dados: O ISAAC, idealizado para maximizar o valor de estudos epidemiológicos em asma e doenças alérgicas, estabeleceu um método padronizado (questionário escrito autoaplicável e/ou vídeo-questionário) capaz de facilitar a colaboração internacional. Concebido para ser realizado em três fases sucessivas e dependentes, o ISAAC reuniu uma casuística até então inimaginável no mundo e no Brasil. Nesta revisão, reuniram-se os dados de centros brasileiros oficiais do ISAAC e de outros que empregaram o seu método. Síntese dos dados: Finalizada a primeira fase, a prevalência de asma entre escolares brasileiros foi documentada como a oitava em magnitude entre todos os centros participantes do estudo. Os poucos centros envolvidos na segunda fase investigaram possíveis fatores etiológicos, especialmente aqueles sugeridos pelos resultados da primeira fase, e geraram muitas especulações. A terceira fase, repetida após sete anos, avaliou a tendência evolutiva da prevalência de asma e das doenças alérgicas nos centros participantes simultaneamente das fases I e III e determinou a prevalência em outros não envolvidos na fase I. Conclusões: No Brasil, o ISAAC demonstrou, de forma definitiva, que a asma é uma doença de alta prevalência e impacto em crianças e adolescentes, devendo ser encarada como problema de Saúde Pública. Encontraram-se importantes variações regionais, ainda não bem esclarecidas, assim como diversos fatores de risco, o que traz a questão: há no Brasil uma ou muitas asmas? .

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.

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 percent confidence intervals (95 percentCI). RESULTS: A significant positive correlation was observed between the prevalence of current asthma and current rhinitis (rs = 0.82; 95 percentCI: 0.60-0.93, p< 0.0001) and between the prevalence of current asthma and current rhinoconjunctivitis (rs = 0.75; 95 percentCI: 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.

Allergic rhinitis: indicators of quality of life.

The objective of this review was to present evidence of the relationship between allergic rhinitis and impairment of quality of life. The data sources were original articles, reviews and consensus statements entered into the Medline and LILACS databases between 1997 and 2008. The following search terms were used: 'allergic rhinitis'; 'quality of life'; and 'sleep disorders'. Quality of life is often impaired in patients with allergic rhinitis, due to the classic symptoms of the disease (sneezing, pruritus, rhinorrhea and nasal obstruction). In addition, the pathophysiology of allergic rhinitis often disrupts sleep, leading to fatigue, irritability, memory deficits, daytime sleepiness and depression. The total burden of this disease goes beyond impairment of physical and social functioning. It has also a financial impact, which becomes greater when we consider the evidence that allergic rhinitis is a possible causal factor of comorbidities, such as asthma and sinusitis. Nasal obstruction, the most prominent symptom, is associated with sleep disorders, which can have a profound effect on mental health, learning, behavior and attention. Finally, allergic rhinitis-a chronic condition that affects adults, adolescents and children-is often underdiagnosed or inadequately treated. The deleterious impact that allergic rhinitis-related sleep disorders have on patient capacity to perform activities of daily living is an important component of the morbidity of the disease. With an accurate diagnosis, there are various available treatments that can reduce the burden of allergic rhinitis.

Rinite alérgica: indicadores de qualidade de vida / Allergic rhinitis: indicators of quality of life

O objetivo desta revisão foi apresentar evidências da relação entre rinite alérgica e redução da qualidade de vida. As fontes de dados foram artigos originais, revisões e consensos indexados nos bancos de dados Medline e LILACS entre 1997 e 2008. As palavras de busca foram "rinite alérgica", "qualidade de vida" e "distúrbios do sono". Os pacientes com rinite alérgica frequentemente têm redução na qualidade de vida causada pelos sintomas clássicos da doença (espirros, prurido, coriza e obstrução). Além disso, a fisiopatologia da rinite alérgica, com frequência, interrompe o sono, ocasionando fadiga, irritabilidade, déficits de memória, sonolência diurna e depressão. A carga total da doença recai não apenas no funcionamento social e físico prejudicados, mas também no impacto financeiro, que se torna maior quando se consideram as evidências de que a rinite alérgica é um possível fator casual de comorbidades, tais como a asma e a sinusite. A obstrução nasal, o mais proeminente dos sintomas, está associada a eventos respiratórios relacionados aos distúrbios do sono, uma condição que tem profundo efeito sobre a saúde mental, o aprendizado, o comportamento e a atenção. Finalmente, a rinite alérgica - doença crônica que afeta crianças, adolescentes e adultos - frequentemente é subdiagnosticada ou inadequadamente tratada. O impacto deletério dos distúrbios do sono associados à rinite alérgica sobre a habilidade para realizar as atividades de vida diária dos pacientes é um importante componente da morbidade da doença. Com um diagnóstico acurado, existem vários tratamentos disponíveis que podem reduzir a carga associada à rinite alérgica.

The objective of this review was to present evidence of the relationship between allergic rhinitis and impairment of quality of life. The data sources were original articles, reviews and consensus statements entered into the Medline and LILACS databases between 1997 and 2008. The following search terms were used: "allergic rhinitis"; "quality of life"; and "sleep disorders". Quality of life is often impaired in patients with allergic rhinitis, due to the classic symptoms of the disease (sneezing, pruritus, rhinorrhea and nasal obstruction). In addition, the pathophysiology of allergic rhinitis often disrupts sleep, leading to fatigue, irritability, memory deficits, daytime sleepiness and depression. The total burden of this disease goes beyond impairment of physical and social functioning. It has also a financial impact, which becomes greater when we consider the evidence that allergic rhinitis is a possible causal factor of comorbidities, such as asthma and sinusitis. Nasal obstruction, the most prominent symptom, is associated with sleep disorders, which can have a profound effect on mental health, learning, behavior and attention. Finally, allergic rhinitis-a chronic condition that affects adults, adolescents and children-is often underdiagnosed or inadequately treated. The deleterious impact that allergic rhinitis-related sleep disorders have on patient capacity to perform activities of daily living is an important component of the morbidity of the disease. With an accurate diagnosis, there are various available treatments that can reduce the burden of allergic rhinitis.

Is the prevalence of asthma and related symptoms among Brazilian children related to socioeconomic status?

OBJECTIVE: To evaluate the relationship between socioeconomic status (SES) and the prevalence of asthma and related symptoms among Brazilian children. METHODS: The International Study of Asthma and Allergies in Childhood (ISAAC) written questionnaire was applied to 23,457 six- to seven-year-old schoolchildren (SC) and 58,144 thirteen- to fourteen-year-old adolescents (AD) from 20 Brazilian cities. SES was evaluated by infant mortality index, poverty index, and average nominal income for people older than 10 years of age. RESULTS: Current asthma ranged from 16.5% to 31.2% among SC and from 11.8% to 30.5% among AD and severe asthma from 2.9% to 8.5% (SC) and 2.6% to 9.1% (AD). Higher values were observed in Brazilian-Northern, -Northeastern and -Southeastern centers. No significant association between SES and prevalence of asthma and related symptoms was observed. CONCLUSIONS: In Brazil, the prevalence of asthma and related symptoms is quite variable and independent of SES.

Abordagem laboratorial no diagnóstico da alergia alimentar: [revisão] / Laboratorial approach in the diagnosis of food allergy: [review]

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 por cento 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.

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 percent 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.

Prevalence of rhinitis among Brazilian schoolchildren: ISAAC phase 3 results.

OBJECTIVE: The International Study of Asthma and Allergies in Childhood (ISAAC) is a standardized method that allows international and regional comparisons of asthma and allergic diseases prevalence. The objective of this study was to evaluate the prevalence of rhinitis and related symptoms among 6-7 year-old children (SC) and 13-14 year-old adolescents (AD) from 20 Brazilian cities applying the ISAAC's standardized written questionnaire (WQ). METHODS: ISAAC's WQ was applied to 23,422 SC and 58,144 AD living in different regions of Brazil: North (N), Northeast (NE), Middle West (MW), Southeast (SE), and South (S). RESULTS: The prevalence of rhinoconjunctivitis in the last year ranged from 10.3% to 17.4% and from 8.9% to 28.5% among SC and AD, respectively. Considering SC the highest values were observed in SE region. In NE, the prevalence in countryside centres was higher than those along the coast. Among AD, the highest values were observed in N and S regions, mainly in Pará (Belém). The evaluation of populations probably with the same genetic background has shown higher prevalence among those living in urban centres (capital) in comparison to those in the countryside. CONCLUSIONS: The prevalence of rhinitis and related symptoms were variable and predominate in Brazilian N and NE centres.