Are pediatricians familiar with hereditary angioedema?

Background: Hereditary angioedema (HAE) is an autosomal dominant disease characterized by recurrent episodes of subcutaneous or mucosal edema caused by excess bradykinin. The aim of the present study was to assess the knowledge of pediatricians about hereditary angioedema. Methods: An online survey with 12 HAE-related and 14 demographics-related questions was e-mailed to all pediatricians who were members of the Brazilian Society of Pediatrics (n = 17 145) once a week during the months of June and July 2021. The electronic questionnaire assessed clinical manifestations, diagnosis, and treatment of hereditary angioedema in children and adolescents. Results: Four hundred and fifty-five pediatricians responded to the questionnaire (2.6%), of whom 55 (12.1%) were board certified in Allergy and Immunology (A/I), while 400 (87.9%) were not (N-A/I). Three hundred and sixty-eight (80.9%) were female, 289 (55.7%) were under 50 years of age, 286 (62.9%) graduated from Medical School more than 10 years previously, 83 (18.2%) held an MSc/PhD degree, and 253 (55.6%) were living in the Southeast Region of Brazil. The median number of correct answers to the questions related to HAE among A/I was 7 out of 12 (58.3%), with median ranging from 4.5 to 8 correct answers, while for N-A/I it was 3 (25%), with median ranging from 2.5 to 4 correct answers (p < 0.001). Conclusion: Knowledge about HAE among Brazilian pediatricians, whether board certified in Allergy and Immunology or not, was unsatisfactory. HAE is a rare disease, largely unknown among physicians; therefore, increasing awareness may lead to improvement in diagnosis and treatment.

Aspectos clínicos e diagnósticos, qualidade de vida, utilidade, adesão terapêutica e custos para angioedema hereditário associado à deficiência de C1-esterase / Clinical and diagnostic aspects, quality of life, usefulness, therapeutic adherence and costs for hereditary angioedema associated with C1-esterase deficiency

Introdução: O angioedema hereditário associado à deficiência de C1 esterase (AEH-C1-INH) é uma doença rara (DR) que se manifesta com a ocorrência de episódios recorrentes de angioedema não pruriginoso subcutâneo ou submucoso, o que gera impactos em todos os aspectos da vida dos indivíduos. Objetivo: Avaliar a qualidade de vida e a jornada clínica e assistencial dos pacientes com AEH-C1-INH. Material e Métodos: Trata-se de um estudo observacional ambispectivo em que foram aplicados questionários relacionados à qualidade de vida e jornada assistencial, além da coleta de dados clínicos dos prontuários nos tempos 0, 6 e 12 meses. Resultados: Foram recrutados 15 indivíduos com AEH-C1-INH e a mediana (I.I.Q) de idade da amostra foi de 38 anos (30-43). O tempo médio entre os primeiros sintomas e o diagnóstico foi de 8 anos. Os dados clínicos demonstraram história familiar positiva expressiva, ocorrência importante de edema de laringe em algum momento da vida e altos índices de recorrência das crises de angioedema durante os 12 meses de estudo. A qualidade de vida apresentou prejuízo importante principalmente em aspectos físicos, emocionais e vitalidade, sem variações significativas no tempo de estudo. Além disso, vale destacar a perda de produtividade expressiva associada a gastos médios de R$3.017,00 para medicamentos e R$598,00 para exames complementares em 12 meses. Conclusão: Observa-se um panorama de perda significativa de qualidade de vida relacionada ao AEH-C1-INH, principalmente por impactos da saúde física e emocional no exercício das atividades rotineiras. Ressaltam-se os impactos econômicos da jornada terapêutica, tanto pela perda de produtividade quanto pela necessidade de financiar medicamentos e exames que deveriam ser responsabilidade do Estado por meio do Sistema Único de Saúde (SUS). Portanto, fica clara a importância de medidas públicas que busquem amenizar os impactos causados pela doença nos indivíduos acometidos.

Introduction: Hereditary Angioedema associated with C1 esterase deficiency (HAE-C1-INH) is a rare disease (RD) that manifests with recurrent episodes of non-pruritic subcutaneous or submucosal angioedema, which impacts on all aspects of the individual's life. Objective: To evaluate the quality of life and the clinical and care journey of patients with HAE-C1-INH. Material and Methods: This is an ambispective observational study in which questionnaires related to quality of life and care journey were applied, in addition to the clinical data collection from medical records at 0, 6 and 12 months. Results: 15 subjects with HAE-C1-INH were recruited and the median (IQR) age of the sample was 38 years (30-43). The average time between the first symptoms and diagnosis was 8 years. The clinical data showed a substantial positive family history, considerable occurrence of laryngeal edema at some point in life and high rates of recurring angioedema crises during the 12 months of the study. Quality of life was significantly impaired, especially in terms of physical and emotional aspects and vitality, with no significant variations over the study period. It is also worth noting the major loss of productivity associated with average costs of R$3,017.00 for medication and R$598.00 for complementary tests over 12 months. Conclusion: There is a noticeable loss of quality of life related to HAE-C1-INH, mainly due to the impact on physical and emotional health when carrying out routine activities. The economic impacts of the therapeutic journey stand out, both due to the loss of productivity and the need to finance medicines and tests that should be the responsibility of the State through the Unified Health System (SUS). Therefore, the importance of public measures that seek to mitigate the impacts caused by the disease on affected individuals is evident.

Reações adversas aos anticorpos monoclonais para doenças alérgicas / Adverse reactions to monoclonal antibodies in allergic diseases

A utilização de agentes imunobiológicos em alergia e imunologia tem sido cada vez mais frequente nos últimos anos, emergindo como potencialmente eficazes para o tratamento de doenças alérgicas e de hipersensibilidade. O uso de imunobiológicos em doenças alérgicas está recomendado nas formas graves onde a eficácia, segurança e custo-efetividade estão comprovados. O objetivo deste artigo é sintetizar os efeitos adversos mais comuns ou significativos, incluindo as reações de hipersensibilidade aos principais anticorpos monoclonais aprovados para o tratamento de doenças alérgicas licenciados e comercializados no Brasil até o momento.

The use of immunobiological agents in allergy and immunology has increased in recent years, emerging as potentially effective strategies to treat allergic and hypersensitivity diseases. The use of immunobiological agents is recommended in the severe forms of allergic diseases, for which their efficacy, safety, and cost-effectiveness have been established. The purpose of this study was to summarize the most common or significant adverse effects, including hypersensitivity reactions to the main monoclonal antibodies approved for the treatment of allergic diseases that are currently licensed and marketed in Brazil.

Guia prático de urticária para grupos especiais de pacientes / Practical guide to urticaria for special patient groups

A urticária crônica é uma condição que afeta mais de um milhão de brasileiros, com grande impacto na qualidade de vida. Mesmo com diretrizes bem difundidas para o seu diagnóstico e tratamento, seu manejo pode ser desafiador em pacientes pediátricos, idosos e gestantes. Para auxiliar o médico especialista nestes casos, o Departamento Científico de Urticária da Associação Brasileira de Alergia e Imunologia elaborou esta revisão com as principais dúvidas e dificuldades referentes ao tema nestes grupos de pacientes.

Chronic urticaria is a condition that affects more than a million Brazilians with a significant impact on quality of life. Although there are well-established guidelines for diagnosis and treatment, the management of chronic urticaria may be challenging in pediatric, older, and pregnant patients. With the purpose of helping specialists manage these cases, the Urticaria Scientific Department of the Brazilian Association of Allergy and Immunology prepared this review with the most common doubts and difficulties about this topic in those patient groups.

Guia prático de urticária aguda / Practical guide to acute urticaria

A urticária aguda é uma causa frequente de consulta com alergistas, caracterizada por urticas e/ou angioedema. Embora autolimitada e benigna, pode causar desconforto significativo e raramente representar uma doença sistêmica grave ou reação alérgica com risco de vida. Nesta revisão, elaborada pelo Departamento Científico de Urticária da Associação Brasileira de Alergia e Imunologia, foram abordadas as principais questões referentes ao tema para auxiliar o médico especialista e generalista.

Acute urticaria is a frequent cause of consultations with allergists, being characterized by wheals and/or angioedema. Although self-limited and benign, it may cause significant discomfort and uncommonly represent a serious systemic disease or life-threatening allergic reaction. In this review prepared by the Urticaria Scientific Department of the Brazilian Association of Allergy and Immunology, the main questions about this topic are addressed to help specialists and general practitioners.

Vacinas COVID-19 e imunobiológicos / COVID-19 vaccines and immunobiological drugs

Os medicamentos imunobiológicos têm sido frequentemente utilizados no tratamento das doenças alérgicas e de natureza imunológica. Esses agentes regulam a resposta imunológica do tipo 2 nas doenças alérgicas ou atuam em diversas vias de ativação alteradas nos erros inatos da imunidade. Com o surgimento da pandemia COVID-19 um crescente número de pacientes em uso de imunobiológicos para essas condições deverão ser vacinados contra o vírus SARS-CoV-2. Dessa forma, existe a necessidade de avaliar a segurança e eficácia destas vacinas nos pacientes em uso de imunobiológicos para asma, dermatite atópica, rinossinusite crônica com pólipos nasais, urticária crônica e erros inatos da imunidade. Foi realizada uma busca de literatura recente relevante sobre imunobiológicos e vacinas COVID-19 no PubMed. Existe um consenso de manutenção desses agentes durante a pandemia COVID-19, embora nas doenças alérgicas os mesmos devam ser suspensos durante a infecção ativa. Por outro lado, dados disponíveis em relação à segurança e eficácia das vacinas contra a COVID-19 nesse grupo de pacientes são escassos. Existem relatos do uso de outras vacinas inativadas em associação com alguns imunobiológicos demonstrando serem eficazes e seguras. Portanto, considerando o risco potencial da infecção COVID-19, especialmente nos pacientes portadores de erros inatos da imunidade, recomendamos que as vacinas contra a COVID-19 sejam utilizadas nos pacientes em uso de imunobiológicos. Desta forma, existe uma necessidade de estudos que avaliem estas questões haja vista que a terapia com diversos imunobiológicos tem sido amplamente utilizada nos pacientes com doenças alérgicas e de natureza imunológica.

Immunobiological drugs have often been used to treat allergic and immunological diseases. These agents regulate the type 2 immune response in allergic diseases or act on different activation pathways altered in inborn errors of immunity. With the emergence of the COVID-19 pandemic, an increasing number of patients with these conditions using these agents should be vaccinated against the SARS-CoV-2 virus. Thus, there is a need to evaluate the safety and efficacy of these vaccines in patients using biologics for asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, chronic urticaria, and inborn errors of immunity. A search for relevant recent literature on biologics and COVID-19 vaccines was conducted on PubMed. There is a consensus on maintaining the use of these agents during the COVID-19 pandemic, although in allergic diseases they must be suspended during active infection. Conversely, the available data regarding the safety and efficacy of the COVID-19 vaccines are scarce. There are reports of the use of other inactivated vaccines with some biologics proving to be effective and safe. Therefore, considering the potential risk of COVID-19 infection, especially in patients with inborn errors of immunity, we recommend that COVID-19 vaccines should be used in patients using biologics. Thus, there is a need for studies to assess these issues, given that therapy with several biologics has been widely used in patients with allergic and immunological diseases.

Vacinação contra COVID-19 em pacientes portadores de angioedema hereditário: recomendações do Grupo de Estudos Brasileiro em Angioedema Hereditário (GEBRAEH) / COVID-19 vaccination in patients with hereditary angioedema: recommendations from the Brazilian Group for the Study on Hereditary Angioedema (GEBRAEH)

No curso da pandemia da COVID-19, o desenvolvimento rápido de vacinas seguras e eficazes é a principal estratégia de saúde pública para conter a propagação da doença. Nesse contexto, esclarecimentos em relação à prioridade e segurança da vacinação contra COVID-19 em pacientes portadores de angioedema hereditário (AEH), assim como de outras doenças, são necessários. Todos os pacientes devem receber a vacina seguindo a estratégia do Ministério da Saúde e manter as medidas de higiene, uso de máscaras e distanciamento social até o controle da pandemia.

During the COVID-19 pandemic, the rapid development of safe and effective vaccines is the main public health strategy to avoid the spread of the disease. In this context, clarifications regarding the priority and safety of vaccination against COVID-19 in patients with hereditary angioedema (HAE), as well as other diseases, are needed. All patients should receive the vaccine according to the Brazilian Ministry of Health strategy and adhere to measures such as maintaining general hygienic measures, wearing masks, and keeping social distance until the pandemic is controlled.

The Challenges in the Follow-Up and Treatment of Brazilian Children with Hereditary Angioedema.

INTRODUCTION: Hereditary angioedema (HAE) with C1 inhibitor (C1-INH) deficiency is a rare autosomal dominant disease. Although the first symptoms can appear in childhood, the diagnosis's delay has a strong impact on the patient's quality of life. We analyzed clinical and laboratory characteristics and the drug therapy of pediatric patients with HAE in Brazil. METHODS: Medical records from 18 reference centers of HAE patients under 18 years of age were evaluated after confirmed diagnosis was performed by quantitative and/or functional C1-INH. RESULTS: A total of 95 participants (51 M:44 F; mean age: 7 years old) out of 17 centers were included; 15 asymptomatic cases were identified through family history and genetic screening. Angioedema attacks affected the extremities (73.5%), gastrointestinal tract (57%), face (50%), lips (42.5%), eyelids (23.7%), genitals (23.7%), upper airways (10%), and tongue (6.3%). Family history was present in 84% of patients, and the mean delay in the diagnosis was 3.9 years. Long-term prophylaxis (51/80) was performed with tranexamic acid (39/80) and androgens (13/80); and short-term prophylaxis (9/80) was performed with tranexamic acid (6/80) and danazol (3/80). On-demand therapy (35/80) was prescribed: icatibant in 7/35, fresh frozen plasma in 16/35, C1-INH plasma-derived in 11/35, and tranexamic acid in 12/35 patients. CONCLUSIONS: This is the first study on HAE pediatric patients in Latin America. Clinical manifestations were similar to adults. Drugs such as androgens and tranexamic acid were indicated off-label, probably due to restricted access to specific drugs. Educational programs should address pediatricians to reduce late diagnosis and tailored child therapy.

Hereditary angioedema: a disease seldom diagnosed by pediatricians.

OBJECTIVES: To describe the hereditary angioedema to improve awareness of this condition and reduce diagnostic delay. DATA SOURCES: Relevant articles in the MEDLINE database through PubMed. DATA SYNTHESIS: Hereditary angioedema is rare and has an autosomal dominant pattern of inheritance. Its onset occurs mainly in childhood, but there is an important delay in the diagnosis. In the most frequent phenotype, there is a quantitative and/or functional deficiency in the C1esterase inhibitor protein, which regulates the activation of the complement, contact and fibrinolysis systems with greater formation of bradykinin, the main mediator of angioedema. There is a third type, the hereditary angioedema with a normal C1 inhibitor level, which is rare in children. Clinical manifestations are characterized by recurrent angioedema attacks, mainly in the extremities, abdomen and upper airways, which can progress to asphyxia and death. The main triggers are mechanical trauma, infections and stress. The diagnosis is attained by patient clinical picture and decreased serum levels of C4 and C1esterase inhibitor or its function. In hereditary angioedema with a normal C1 inhibitor, there is no change in these parameters, thus requiring a genetic study. Treatment is based on the use of attack medications and long and short-term prophylaxis. CONCLUSIONS: Hereditary angioedema is little known by pediatricians due to the significant delay in diagnosis of this condition, whose onset usually begins in childhood. The presence of recurrent angioedema that does not respond to treatment with antihistamines, corticosteroids and adrenaline should increase the diagnostic suspicion.

Guia prático do tratamento com omalizumabe para urticária crônica espontânea / Practical guide to omalizumab treatment for chronic spontaneous urticaria

A urticária crônica é uma doença com grande impacto socioeconômico e na qualidade de vida do indivíduo. O adequado conhecimento de formas de tratamento eficazes e com perfil de segurança satisfatório, assim como dos mecanismos preditores de resposta ao tratamento, são essenciais para que se alcance um controle adequado da doença. O omalizumabe é um anticorpo monoclonal anti-IgE com eficácia reconhecida e bom perfil de segurança no tratamento da urticária crônica. Objetivamos elucidar questões envolvidas no manejo desta medicação, através da revisão em literatura de estudos atuais e com relevância clínica. Foi realizado levantamento de questões importantes e pouco elucidadas, buscando respostas baseadas nestes estudos. Com isso, foram abordados aspectos práticos do tratamento com o omalizumabe, esclarecendo desde os fenótipos dos pacientes e conduta adequada para estas diferentes situações, trazendo possíveis fatores preditores de resposta ao tratamento e contemplando também um novo anticorpo monoclonal anti-IgE no manejo destes pacientes.

Chronic urticaria is a disease with great socioeconomic impact on people's quality of life. Adequate knowledge of effective treatments with a satisfactory safety profile as well as of the predictive mechanisms of response to treatment are essential for achieving adequate disease control. Omalizumab is an anti-IgE monoclonal antibody with recognized efficacy and a good safety profile in the treatment of chronic urticaria. We aim to elucidate issues involving the management of this medication through a literature review of current studies with clinical relevance. A survey of important and unclear questions was conducted, and the answers were sought in the studies. Thus, practical aspects of omalizumab treatment were addressed, including the phenotypes of patients and appropriate approaches for different situations. Possible predictive factors of response to treatment and a new anti-IgE monoclonal antibody for the management of these patients were also reported.

Perfil dos portadores de urticária crônica do hospital universitário de Salvador-BA / Profile of patients with chronic urticaria at the University Hospital of Salvador-BA

Introdução: A urticária crônica é caracterizada pela presença de placas eritematosas cutâneas com prurido por mais de 6 semanas, com ou sem angioedema. Estudos indicam que essa afecção afeta cerca de 1% da população mundial, sendo que a maior parte desses casos de causas idiopáticas. A qualidade de vida em pacientes com urticária pode ser gravemente prejudicada. Os objetivos desse estudo são caracterizar o perfil epidemiológico da urticária crônica dentro de um serviço especializado público no estado da Bahia, bem como avaliar a influência dessa disfunção na qualidade de vida desses pacientes. Métodos: Trata-se de um estudo descritivo observacional a partir de informações extraídas dos prontuários de 135 pacientes atendidos no serviço de Alergia e Imunologia do Ambulatório Magalhães Neto, pertencente ao Complexo do Hospital Universitário Edgard Santos da Universidade Federal da Bahia. Resultados: Indivíduos do sexo feminino representam 80,0% do número total de participantes desse estudo; 71 indivíduos (52,6%) têm mais de 45 anos de idade; foi verificada a presença de angioedema associado à urticária em 52,0% dos participantes. O tempo médio do início dos sintomas associados à doença foi de 7,3 anos, e o tempo médio de diagnóstico da doença foi de 4,4 anos. Com relação à presença de comorbidades, a mais prevalente foi a rinite alérgica (27,0%). O fármaco mais utilizado no tratamento desses participantes foi a Cetirizina, que foi prescrita em 36,0% dos casos. Para 31% a urticária crônica espontânea afeta muito a sua qualidade de vida. Conclusões: O perfil dos participantes desse estudo se assemelha ao de outros em estudos realizados no mundo. A urticária crônica impacta predominantemente de forma moderada a qualidade de vida, e mais fortemente as dimensões sono/estado mental e alimentação.

Introduction: Chronic urticaria is characterized by the presence of erythematous skin plaques with pruritus for more than 6 weeks, with or without angioedema. Studies indicate that this condition affects about 1% of the world population, with idiopathic causes accounting for most cases. Quality of life in patients with urticaria can be severely impaired. The objectives of this study were to characterize the epidemiological profile of chronic urticaria within a specialized public service in the state of Bahia and to evaluate the influence of this disorder on the quality of life of these patients. Methods: This was an observational descriptive study based on information extracted from the medical records of 135 patients seen at the Department of Allergy and Immunology of the Magalhaes Neto Outpatient Clinic, which belongs to the Edgard Santos University Hospital Complex of the Federal University of Bahia. Results: Women accounted for 80.0% of the sample; 71 individuals (52.6%) were over 45 years of age. Presence of angioedema was associated with urticaria in 52.0% of participants. The mean time to the onset of disease-associated symptoms was 7.3 years, and the mean time to disease diagnosis was 4.4 years. Regarding the presence of comorbidities, allergic rhinitis was the most prevalent disorder (27.0%). Cetirizine was the most commonly used drug for treatment, being prescribed in 36.0% of cases. Chronic spontaneous urticaria was reported to greatly affect quality of life by 31% of participants. Conclusions: The profile of the participants in this study resembles that of participants in studies conducted worldwide. Overall, chronic urticaria has a moderate impact on quality of life and a stronger impact on the dimensions of sleep / mental state and diet.

Ferramentas para avaliação e acompanhamento da urticária crônica / Patient-reported outcomes for the evaluation and follow-up of chronic urticaria

Urticária é uma doença pruriginosa da pele na qual ocorrem urticas e/ou angioedema. A urticária é definida como crônica quando persiste por 6 semanas ou mais. A urticária crônica tem um grande impacto na vida diária do paciente. Atualmente, não há biomarcadores confiáveis para identificar e medir a atividade da doença na urticária crônica espontânea. Consequentemente, o uso de ferramentas conhecidas por patient-reported outcomes (PROs) é crucial ao avaliar e monitorar diferentes aspectos da urticária crônica, como atividade/gravidade da doença, controle da doença e qualidade de vida. Apresentamos uma visão geral de cinco PROs usados na avaliação da urticária crônica, e destacamos suas vantagens, limitações e uso na prática clínica e pesquisa.

Urticaria is an itching skin disease characterized by the presence of wheals and/or angioedema. Urticaria is defined as chronic when it persists for 6 weeks or more. Chronic urticaria has great impact on the daily lives of patients. Currently, there are no reliable biomarkers to identify and measure disease activity in chronic spontaneous urticaria. Consequently, the use of tools known as patient-reported outcomes (PROs) is crucial when evaluating and monitoring different aspects of chronic urticaria such as disease activity/severity, disease control, and quality of life. We present an overview of the five PROs used in the evaluation of chronic urticaria, highlighting their advantages, limitations, and use in clinical practice and research.

Influence of upper airway abnormalities on the control of severe asthma: a cross-sectional study.

BACKGROUND: A better understanding of severe uncontrolled asthma (UA) in the upper airways is needed. The aims of this study were to assess the prevalence of upper airway abnormalities and their associations with UA. METHODS: An observational study enrolled individuals with severe asthma. Sociodemographic and clinical questionnaires regarding asthma, rhinosinusitis, and laryngopharyngeal reflux (LPR) were administered. Skin-prick tests and fiber optic nasolaryngoscopies were also performed. Descriptive statistical analysis was performed, using a multiple Poisson regression model to obtain adjusted prevalence ratios (PRs) and to identify the clinical profiles associated with the highest and lowest percentages of the dependent variable, lack of asthma control. RESULTS: The sample consisted of 64 participants who were divided into 2 groups according to asthma control. Thus, group I comprised 27 individuals with severe controlled asthma (CA), and group II consisted of 37 individuals with UA. Women represented 87.5% of the study population. The median age was 54 years, and 86% of the sample had rhinosinusitis. Relevant associations were detected between UA and hyposmia (PR = 2.04), hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) (PR = 1.45), arytenoids hyperemia (PR = 1.45), LPR (PR = 1.37), a positive family history of asthma (PR = 1.35), onset of asthma at age 10 years or older (PR = 0.59), and swelling of the vocal cords (PR = 0.54). CONCLUSION: This study found a very high prevalence of rhinosinusitis in patients with severe asthma as well as associations between UA and hyposmia, hypersensitivity to NSAIDs, arytenoids hyperemia, and LPR. Clinical profiles prone to UA were identified.