Recent findings on drug hypersensitivity in children.

Drug hypersensitivity reactions (DHR) in children have a significant impact on clinical practice and public health. Both under-diagnosis (due to under-reporting) and over-diagnosis (due to the overuse of the term "allergy") are potential issues. The aim of this narrative review is to describe the most recent findings of DHR in children/adolescents and gaps regarding epidemiology, antibiotic allergy, antiepileptic hypersensitivity, vaccine allergy, and severe cutaneous adverse reactions (SCAR) in this age group.

Asma em adolescentes: o que o estudo ERICA nos mostrou? / Asthma in adolescents: what did ERICA study show us?

A asma é uma doença heterogênea caracterizada pela história de sintomas respiratórios que variam de intensidade e ao longo do tempo. Devido à sua alta prevalência, constitui um problema mundial de saúde pública, atingindo todas as faixas etárias, em especial crianças e adolescentes. O objetivo deste artigo foi analisar as produções científicas sobre asma baseadas no Estudo de Riscos Cardiovasculares em Adolescentes (ERICA). Trata-se de uma revisão narrativa incluindo os artigos originais sobre asma baseados nos dados do ERICA, publicados em periódicos indexados em inglês e português. O ERICA foi um estudo multicêntrico nacional realizado em 2013 e 2014, que investigou a prevalência de asma e fatores de risco cardiovascular, incluindo obesidade, diabetes mellitus, hipertensão arterial sistêmica, dislipidemia, tabagismo, sedentarismo, hábitos alimentares inadequados, e a associação entre esses fatores, em adolescentes de 12 a 17 anos, estudantes de escolas públicas e privadas de municípios brasileiros com mais de 100.000 habitantes. Nos cinco estudos selecionados, foi possível demonstrar que a prevalência de asma foi significativamente maior entre adolescentes do sexo feminino em todas as capitais e macrorregiões do Brasil, com predomínio da doença na região Sudeste do nosso país. Além disso, a asma esteve fortemente associada ao tabagismo (passivo e ativo) e foi associada à duração curta do sono. Por outro lado, não esteve associada com os níveis séricos de vitamina D. Em relação aos parâmetros metabólicos, foi observado que a síndrome metabólica e alguns de seus componentes, como a circunferência abdominal, estiveram significativamente associados à asma grave em adolescentes brasileiros.

Asthma is a heterogeneous disease characterized by a history of respiratory symptoms that vary in intensity and over time. Due to its high prevalence, asthma is considered a global public health problem affecting all age groups, especially children and adolescents. This study aimed to analyze scientific papers on asthma based on the Study of Cardiovascular Risks in Adolescents (ERICA). We provide a narrative review of original articles on asthma based on ERICA data published in indexed journals in English and Portuguese. ERICA was a national multicenter study conducted in 2013 and 2014 that investigated the prevalence of asthma and cardiovascular risk factors, including obesity, diabetes mellitus, systemic arterial hypertension, dyslipidemia, smoking, sedentary lifestyle, and inadequate eating habits, and the association between these factors in adolescents aged 12 to 17 years, students from public and private schools in Brazilian cities of more than 100,000 population. In the 5 selected studies, the prevalence of asthma was significantly higher in female adolescents in all capitals and macro-regions of Brazil, occurring predominantly in the southeast region of the country. In addition, asthma was strongly associated with smoking (passive and active) as well as with short sleep duration, but not with serum vitamin D levels. Regarding metabolic parameters, metabolic syndrome and some of its components, such as waist circumference, were significantly associated with severe asthma in Brazilian adolescents.

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.

Acute Urticaria and Anaphylaxis: Differences and Similarities in Clinical Management.

Acute urticaria is a common condition that presents with wheals and/or angioedema. However, these symptoms are also frequent in anaphylaxis, a life-threatening reaction that should be immediately diagnosed and treated. In both, mast cells play a central role in the physiopathology. Causes and triggers of acute urticaria and anaphylaxis are similar in general, but some peculiarities can be observed. The diagnostic approach may differ, accordingly to the condition, suspicious causes, age groups and regions. Adrenaline is the first-line treatment for anaphylaxis, but not for acute urticaria, where H1-antihistamines are the first choice. In this paper, we review the main aspects, similarities and differences regarding definitions, mechanisms, causes, diagnosis and treatment of acute urticaria and anaphylaxis.

Desensitization to drugs in children.

Better knowledge and understanding about drug desensitization is required in the pediatric population, since there is little literature available about it and the most pediatric desensitization protocols have been adapted from adult instructions.Aiming to soften this issue and foster the future studies, this article presents a recent review about mechanisms of desensitization, diagnostic tools, and up to date management of drug hypersensitivity reactions in children. Bringing up an overview of pediatric hypersensitivity reactions to chemotherapy, biologic agents, antibiotics, nonsteroidal anti-inflammatory drugs, and vaccines.

Desensitization to drugs in children

Better knowledge and understanding about drug desensitization is required in the pediatric population, since there is little literature available about it and the most pediatric desensitization protocols have been adapted from adult instructions.Aiming to soften this issue and foster the future studies, this article presents a recent review about mechanisms of desensitization, diagnostic tools, and up to date management of drug hypersensitivity reactions in children. Bringing up an overview of pediatric hypersensitivity reactions to chemotherapy, biologic agents, antibiotics, nonsteroidal anti-inflammatory drugs, and vaccines (AU)

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.

Asthma and vitamin D in Brazilian adolescents: Study of Cardiovascular Risks in Adolescents (ERICA).

OBJECTIVE: To evaluate the association between asthma prevalence and serum levels of vitamin D in Brazilian adolescents. METHODS: This was a cross-sectional, school-based study involving adolescents between 12-17 years of age from four large Brazilian cities located at different latitudes (Fortaleza, Rio de Janeiro, Brasília, and Porto Alegre). Information on asthma diagnosis, lifestyle, and sociodemographic characteristics was collected by means of self-administered questionnaires. Serum concentrations of calcifediol were dichotomized as sufficient (≥ 20 ng/mL) or insufficient/deficient (< 20 ng/mL) levels. Bivariate analyses were carried out between vitamin D levels and prevalence of active asthma (AA), as well as other variables in study, using the chi-square test. Generalized linear models were configured to analyze potential confounding factors (p < 0.20). RESULTS: Between 2013 and 2014, 1,053 adolescents were evaluated. The prevalences of AA and insufficient/deficient levels of calcifediol were 15.4% and 21%, respectively. There were no statistically significant associations between AA and hypovitaminosis D. The prevalences of AA and vitamin D insufficiency were, respectively, 2.34 (95% CI, 1,28-4.30) and 3.22 (95% CI, 1.75-5.95) times higher in Porto Alegre than in Rio de Janeiro, regardless of possible confounding factors. However, no significant associations were found between the prevalence of AA and vitamin-D-related variables in any of the cities. CONCLUSIONS: No association was found between AA and low levels of vitamin D in adolescents living at different latitudes in Brazil.

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.

Resposta ao dupilumabe na dermatite atópica grave sem uso prévio de imunossupressor sistêmico durante a pandemia de COVID-19 / Response to dupilumab in severe atopic dermatitis without prior use of systemic immunosuppressive agents during the COVID-19 pandemic

A dermatite atópica (DA) é uma doença inflamatória crônica da pele, caracterizada por intenso prurido e eczema recorrente. Acomete principalmente a infância, mas tem se tornado bastante prevalente em adolescentes e até em adultos. Apesar de ser geralmente não fatal, apresenta uma carga psicossocial importante para os pacientes e seus familiares. O tratamento da DA envolve a hidratação cutânea e medicações anti-inflamatórias. Em casos graves, pode haver necessidade de terapia sistêmica com imunossupressores como ciclosporina, metotrexato e azatioprina. Mais recentemente, alguns imunobiológicos estão em desenvolvimento para controle da DA. O dupilumabe é um anticorpo monoclonal com ação dupla anti-IL-4/IL-13, liberado para tratamento de crianças a partir de 6 anos com DA grave e adolescentes/adultos com DA moderada a grave. O objetivo deste artigo foi relatar uma série de casos de pacientes adolescentes e adultos com DA grave e sua resposta ao dupilumabe durante a pandemia do COVID-19. Trata-se de quatro pacientes (três do sexo feminino), com piora significativa da DA durante o ano de 2020. Todos tinham história de DA desde a infância, com exames complementares evidenciando sensibilização IgE-mediada para ácaros. Já haviam sido submetidos a diversos tratamentos tópicos e sistêmicos, inclusive a cursos de corticosteroides orais. Nenhum deles havia recebido imunossupressor sistêmico, porém estavam recusando este tipo de tratamento devido ao medo da pandemia. Todos apresentaram boa resposta ao dupilumabe, evidenciada pela redução do número de lesões cutâneas e prurido, com poucos efeitos colaterais. Dois pacientes apresentaram sintomas sugestivos de COVID-19 durante o tratamento com dupilumabe (um com confirmação por PCR), com boa evolução. Concluindo, os pacientes com DA grave possuem grande impacto na qualidade de vida e, durante a pandemia de COVID-19, muitos apresentaram piora significativa do seu quadro dermatológico. Nesse contexto, o dupilumabe se mostrou uma opção terapêutica eficaz e segura para tratamento destes pacientes.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by intense itching and recurrent eczema. It mainly affects childhood but has become quite prevalent in adolescents and even adults. Despite being generally nonfatal, it has an important psychosocial burden for patients and their families. AD treatment involves skin hydration and antiinflammatory medications. In severe cases, systemic therapy with immunosuppressive agents such as cyclosporine, methotrexate, and azathioprine may be necessary. More recently, some biologicals are being developed to control AD. Dupilumab is a monoclonal antibody with anti-IL-4/IL-13 dual-action, approved for the treatment of children from 6 years of age with severe AD and adolescents/adults with moderate to severe AD. This article aimed to report a case series of adolescent and adult patients with severe AD and their response to dupilumab during the COVID-19 pandemic. These are four patients (three female), with a significant worsening of AD during the year 2020. All had a history of AD since childhood, with complementary exams showing IgE-mediated sensitization to mites. They had already undergone several topical and systemic treatments, including courses on oral corticosteroids. None of them had received systemic immunosuppressive agents, but they were refusing this type of treatment due to fear of the pandemic. All had a good response to dupilumab, evidenced by a reduction in the number of skin lesions and pruritus, with few side effects. Two patients had symptoms suggestive of COVID-19 during treatment with dupilumab (one confirmed by PCR) with a good outcome. In conclusion, patients with severe AD have a great impact on quality of life and, during the COVID-19 pandemic, many had a significant worsening of their dermatological condition. In this context, dupilumab proved to be an effective and safe therapeutic option for the treatment of these patients.

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.

Erupção fixa bolhosa generalizada após reexposição à dipirona: relato de caso e revisão da literatura / Generalized bullous fixed drug eruption after reexposure to dipyrone: a case report and literature review

A erupção fixa à droga (EFD) é uma reação de hipersensibilidade tardia a medicamentos caracterizada por máculas ou pápulas eritematosas, violáceas ou acastanhadas, bem demarcadas, que aparecem após uso de uma medicação, e reaparecem na mesma localização após exposições repetidas. A erupção fixa à droga bolhosa generalizada (EFDBG) é uma variante rara da EFD que foi recentemente incluída pelo RegiSCAR no grupo das farmacodermias graves. Apresenta-se através de lesões cutâneas generalizadas características de EFD, com formação de bolhas, geralmente em pacientes com história prévia de EFD. Os principais medicamentos envolvidos na EFDBG são antibióticos e anti-inflamatórios não esteroidais. O diagnóstico é clínico, entretanto, a biópsia cutânea na fase aguda e o teste de contato após a recuperação do paciente, podem auxiliar a investigação. O tratamento requer geralmente apenas a suspensão do fármaco suspeito e medidas de suporte. Relatamos um caso de EFDBG em adolescente após reexposição à dipirona (metamizol) apesar da história prévia de hipersensibilidade a esta medicação. O objetivo deste relato é alertar sobre a importância do diagnóstico da EFDBG e ressaltar os principais pontos para o diagnóstico diferencial com a síndrome de Stevens-Johnson (SSJ)/necrólise epidérmica tóxica (NET).

Fixed drug eruption (FDE) is a delayed drug hypersensitivity reaction characterized by erythematous, violaceous or brownish well-demarcated macules or papules that appear after use of a medication and reappear at the same site after repeated exposures. Generalized bullous fixed drug eruption (GBFDE) is a rare FDE variant that has been recently included by RegiSCAR in the group of severe cutaneous adverse reactions to drugs. GBFDE presents as generalized cutaneous lesions characteristic of FDE, with blistering, usually in patients with a previous history of FDE. The main drugs involved in GBFDE are antibiotics and nonsteroidal anti-inflammatory drugs. The diagnosis is clinical, but some tests can help the investigation, such as skin biopsy in the acute phase and patch testing after patient recovery. Treatment usually requires suspension of the suspected drug and some supportive measures. We report a case of GBFDE after reexposure to dipyrone (metamizole) in an adolescent with a previous history of hypersensitivity to this drug. The aim of this report is to warn about the importance of diagnosing GBFDE and to highlight the main points for differential diagnosis with Stevens- Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN).

ERICA: smoking is associated with more severe asthma in Brazilian adolescents / ERICA: tabagismo está associado a asma mais grave em adolescentes brasileiros

Abstract Objective: To investigate the association between smoking and asthma, and possible associated factors in Brazilian adolescents. Methods: A cross-sectional, national, school-based study with adolescents aged 12-17 years, participants in the Study of Cardiovascular Risks in Adolescents (Estudo de Riscos Cardiovasculares em Adolescentes - ERICA). A total of 66,394 participants answered a self-administered questionnaire with questions about asthma, smoking, lifestyle and sociodemographic variables. Bivariate analysis between Current Asthma (CA) and Severe Asthma (SA) and the other study variables were performed using Chi-squared. Then, the crude and adjusted Prevalence Ratios (PR), and respective 95% Confidence Intervals (95% CI) of current asthma/severe asthma and smoking variables, corrected for sociodemographic and lifestyle variables, were estimated using generalized linear models with Poisson regression, logit link, and robust variance. Results: The prevalence of current asthma and severe asthma were significantly higher in adolescents who were exposed to: experimentation (current asthma: PR = 1.78, 95% CI: 1.51-2.09; severe asthma: PR = 2.01; 95% CI: 1.35-2.98); current smoking (current asthma: PR = 2.08, 95% CI: 1.65-2.64; severe asthma: PR = 2.29; 95% CI: 1.38-3.82); regular smoking (current asthma: PR = 2.25, 95% CI: 1.64-3.07; severe asthma: PR: 2.41; 95% CI: 1.23-4.73); and passive smoking (current asthma: PR = 1.47, 95% CI: 1.27-1.67; severe asthma: PR = 1.66; 95% CI: 1.19-2.32); these associations remained significant after adjustment. Conclusions: Asthma and smoking were significantly associated in Brazilian adolescents, regardless of the sociodemographic and lifestyle factors, notably in those with more severe disease.

Resumo: Objetivo: Investigar a associação entre asma, tabagismo e possíveis fatores associados em adolescentes brasileiros. Métodos: Estudo transversal, nacional, de base escolar, envolveu adolescentes com 12 a 17 anos, participantes do Estudo de Riscos Cardiovasculares em Adolescentes (ERICA). Os 66.394 participantes responderam questionários autopreenchíveis com questões sobre asma, tabagismo, estilo de vida e dados sociodemográficos. Foram realizadas análises bivariadas entre asma ativa e asma grave e demais variáveis do estudo, com o uso de χ2. Em seguida, foram estimadas as razões de prevalência (RP) brutas e ajustadas e seus respectivos intervalos de confiança de 95% (IC 95%), entre asma ativa/asma grave e variáveis de tabagismo, corrigidas pelas variáveis sociodemográficas e de estilo de vida, através de modelos lineares generalizados com regressão de Poisson, função de ligação logarítmica e variância robusta. Resultados: A prevalência de asma ativa e asma grave foi significativamente mais elevada naqueles expostos a experimentação (asma ativa: RP = 1,78; IC 95%: 1,51-2,09; asma grave: RP = 2,01; IC 95%: 1,35-2,98); tabagismo atual (asma ativa: RP = 2,08; IC 95%: 1,65-2,64; asma grave: RP = 2,29; IC 95%: 1,38-3,82); tabagismo frequente (asma ativa: RP = 2,25; IC 95%: 1,64-3,07; AG = 2,41; IC 95%: 1,23-4,73) e tabagismo passivo (asma ativa: RP = 1,47; IC 95%: 1,27-1,67; asma grave: RP = 1,66; IC 95%: 1,19-2,32). As associações permaneceram significativas após ajuste. Conclusão: A asma e o tabagismo se associaram de modo significativo em adolescentes brasileiros independente de fatores sociodemográficos e estilo de vida, especialmente naqueles com doença mais grave.

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.

ERICA: smoking is associated with more severe asthma in Brazilian adolescents.

OBJECTIVE: To investigate the association between smoking and asthma, and possible associated factors in Brazilian adolescents. METHODS: A cross-sectional, national, school-based study with adolescents aged 12-17 years, participants in the Study of Cardiovascular Risks in Adolescents (Estudo de Riscos Cardiovasculares em Adolescentes - ERICA). A total of 66,394 participants answered a self-administered questionnaire with questions about asthma, smoking, lifestyle and sociodemographic variables. Bivariate analysis between Current Asthma (CA) and Severe Asthma (SA) and the other study variables were performed using Chi-squared. Then, the crude and adjusted Prevalence Ratios (PR), and respective 95% Confidence Intervals (95% CI) of current asthma/severe asthma and smoking variables, corrected for sociodemographic and lifestyle variables, were estimated using generalized linear models with Poisson regression, logit link, and robust variance. RESULTS: The prevalence of current asthma and severe asthma were significantly higher in adolescents who were exposed to: experimentation (current asthma: PR=1.78, 95% CI: 1.51-2.09; severe asthma: PR=2.01; 95% CI: 1.35-2.98); current smoking (current asthma: PR=2.08, 95% CI: 1.65-2.64; severe asthma: PR=2.29; 95% CI: 1.38-3.82); regular smoking (current asthma: PR=2.25, 95% CI: 1.64-3.07; severe asthma: PR: 2.41; 95% CI: 1.23-4.73); and passive smoking (current asthma: PR=1.47, 95% CI: 1.27-1.67; severe asthma: PR=1.66; 95% CI: 1.19-2.32); these associations remained significant after adjustment. CONCLUSIONS: Asthma and smoking were significantly associated in Brazilian adolescents, regardless of the sociodemographic and lifestyle factors, notably in those with more severe disease.

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.