Definition, acronyms, nomenclature, and classification of angioedema (DANCE): AAAAI, ACAAI, ACARE, and APAAACI DANCE consensus.

BACKGROUND: Angioedema (AE) manifests with intermittent, localized, self-limiting swelling of the subcutaneous and/or submucosal tissue. AE is heterogeneous, can be hereditary or acquired, may occur only once or be recurrent, may exhibit wheals or not, and may be due to mast cell mediators, bradykinin, or other mechanisms. Several different taxonomic systems are currently used, making it difficult to compare the results of studies, develop multicenter collaboration, and harmonize AE treatment. OBJECTIVE: We developed a consensus on the definition, acronyms, nomenclature, and classification of AE (DANCE). METHODS: The initiative involved 91 experts from 35 countries and was endorsed by 53 scientific and medical societies, and patient organizations. A consensus was reached by online discussion and voting using the Delphi process over a period of 16 months (June 2021 to November 2022). RESULTS: The DANCE initiative resulted in an international consensus on the definition, classification, and terminology of AE. The new consensus classification features 5 types and endotypes of AE and a harmonized vocabulary of abbreviations/acronyms. CONCLUSION: The DANCE classification complements current clinical guidelines and expert consensus recommendations on the diagnostic assessment and treatment of AE. DANCE does not replace current clinical guidelines, and expert consensus algorithms and should not be misconstrued in a way that affects reimbursement of medicines prescribed by physicians using sound clinical judgment. We anticipate that this new AE taxonomy and nomenclature will harmonize and facilitate AE research and clinical studies, thereby improving patient care.

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.

Diretrizes brasileiras do angioedema hereditário 2022 ­ Parte 1: definição, classificação e diagnóstico / 2022 Brazilian guidelines for hereditary angioedema ­ Part 1: definition, classification, and diagnosis

O angioedema hereditário é uma doença autossômica dominante caracterizada por crises recorrentes de edema que acometem o tecido subcutâneo e o submucoso, com envolvimento de diversos órgãos. Os principais locais afetados são face, membros superiores e inferiores, as alças intestinais e as vias respiratórias superiores. Em decorrência da falta de conhecimento dessa condição por profissionais de saúde, ocorre atraso importante no seu diagnóstico, comprometendo a qualidade de vida dos indivíduos afetados. Além disso, o retardo no diagnóstico pode resultar em aumento da mortalidade por asfixia devido ao edema de laringe. A natureza errática das crises com variação do quadro clínico e gravidade dos sintomas entre diferentes pacientes, e no mesmo paciente ao longo da vida, se constitui em desafio no cuidado dos doentes que têm angioedema hereditário. O principal tipo de angioedema hereditário é resultante de mais de 700 variantes patogênicas do gene SERPING1 com deficiência funcional ou quantitativa da proteína inibidor de C1, porém nos últimos anos outras mutações foram descritas em seis outros genes. Ocorreram avanços importantes na fisiopatologia da doença e novas drogas para o tratamento do angioedema hereditário foram desenvolvidas. Nesse contexto, o Grupo de Estudos Brasileiro em Angioedema Hereditário (GEBRAEH) em conjunto com a Associação Brasileira de Alergia e Imunologia (ASBAI) atualizou as diretrizes brasileiras do angioedema hereditário. O maior conhecimento dos diversos aspectos resultou na divisão das diretrizes em duas partes, sendo nessa primeira parte abordados a definição, a classificação e o diagnóstico.

Hereditary angioedema is an autosomal dominant disease characterized by recurrent attacks of edema that affect the subcutaneous tissue and the submucosa, involving several organs. The main affected sites are the face, upper and lower limbs, gastrointestinal tract, and upper airways. Because health professionals lack knowledge about this condition, there is a significant delay in diagnosis, compromising the quality of life of affected individuals. Furthermore, delayed diagnosis may result in increased mortality from asphyxia due to laryngeal edema. The erratic nature of the attacks with variations in clinical course and severity of symptoms among different patients and in one patient throughout life constitutes a challenge in the care of patients with hereditary angioedema. The main type of hereditary angioedema results from more than 700 pathogenic variants of the SERPING1 gene with functional or quantitative deficiency of the C1 inhibitor protein, but in recent years other mutations have been described in six other genes. Important advances have been made in the pathophysiology of the disease, and new drugs for the treatment of hereditary angioedema have been developed. In this context, the Brazilian Study Group on Hereditary Angioedema (GEBRAEH) in conjunction with the Brazilian Association of Allergy and Immunology (ASBAI) updated the Brazilian guidelines on hereditary angioedema. Greater knowledge of different aspects resulted in the division of the guidelines into two parts, with definition, classification, and diagnosis being addressed in this first part.

Diretrizes brasileiras de angioedema hereditário 2022 ­ Parte 2: terapêutica / 2022 Brazilian guidelines for hereditary angioedema ­ Part 2: therapy

O tratamento do angioedema hereditário tem início com a educação dos pacientes e familiares sobre a doença, pois é fundamental o conhecimento da imprevisibilidade das crises, assim como os seus fatores desencadeantes. O tratamento medicamentoso se divide em terapia das crises e profilaxia das manifestações clínicas. As crises devem ser tratadas o mais precocemente possível com o uso do antagonista do receptor de bradicinina, o icatibanto ou o concentrado de C1-inibidor. É necessário estabeler um plano de ação em caso de crises para todos os pacientes. A profilaxia de longo prazo dos sintomas deve ser realizada preferencialmente com medicamentos de primeira linha, como concentrado do C1-inibidor ou o anticorpo monoclonal anti-calicreína, lanadelumabe. Como segunda linha de tratamento temos os andrógenos atenuados. Na profilaxia de curto prazo, antes de procedimentos que podem desencadear crises, o uso do concentrado de C1-inibidor é preconizado. Existem algumas restrições para uso desses tratamentos em crianças e gestantes que devem ser consideradas. Novos medicamentos baseados nos avanços do conhecimento da fisiopatologia do angioedema hereditário estão em desenvolvimento, devendo melhorar a qualidade de vida dos pacientes. O uso de ferramentas padronizadas para monitorização da qualidade de vida, do controle e da atividade da doença são fundamentais no acompanhamento destes pacientes. A criação de associações de pacientes e familiares de pacientes com angioedema hereditário tem desempenhado um papel muito importante no cuidado destes pacientes no nosso país.

The treatment of hereditary angioedema begins with the education of patients and their families about the disease, as it is essential to know the unpredictability of attacks as well as their triggering factors. Drug treatment is divided into attack therapy and prophylaxis of clinical manifestations. Attacks should be treated as early as possible with the bradykinin receptor antagonist icatibant or C1-inhibitor concentrate. An action plan needs to be established for all patients with attacks. Long-term prophylaxis of symptoms should preferably be performed with first-line drugs such as C1-inhibitor concentrate or the anti-kallikrein monoclonal antibody lanadelumab. Attenuated androgens are the second line of treatment. In short-term prophylaxis, before procedures that can trigger attacks, the use of C1-inhibitor concentrate is recommended. There are some restrictions for the use of these treatments in children and pregnant women that should be considered. New drugs based on advances in knowledge of the pathophysiology of hereditary angioedema are under development and are expected to improve patient quality of life. The use of standardized tools for monitoring quality of life and controlling disease activity is essential in the follow-up of these patients. The creation of associations of patients and families of patients with hereditary angioedema has played a very important role in the care of these patients 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.

Pregnancy in Patients With Hereditary Angioedema and Normal C1 Inhibitor.

Background: HAE with normal C1 inhibitor (HAE-nC1-INH) has been identified as a bradykinin mediated angioedema. Estrogens are one of the main trigger factors. Pregnancy in HAE with C1 inhibitor deficiency showed variable course, however, few reports are available for HAE-nC1-INH. We evaluated the course of pregnancies in women diagnosed with HAE-nC1-INH. Methods: Women with diagnosis of HAE-nC1-INH according to the following criteria: clinical manifestations similar to HAE-C1-INH, normal biochemical evaluation and family history were included. A questionnaire about pregnancies was applied after consent. Genetic evaluation for known mutations was performed in all patients. Results: A total of 45 pregnancies occurring in 26 HAE-nC1-INH patients were evaluated (7/26 patients with F12 variant). Spontaneous abortion was reported in 8/45 (17.8%) pregnancies. Onset of attacks started before the pregnancy in 18/26 patients; during the pregnancy in 2/26; and after the pregnancy in 6/26. HAE attacks occurred in 24/37 pregnancies (64,7%): during the 1st trimester in 41.7%; 2nd trimester in 12.5%; 3rd trimester in 20.8%; 1st and 3rd trimesters in 4.2% and during the whole pregnancy in 20.8%. Among 15/18 patients who had attacks before pregnancy, symptoms persisted with worsening in 9/15; improvement in 4/15; no change in 1/15, and no response in 1/15. Conclusions: The occurrence of abortion in HAE-nC1-INH was similar to the expected for not affected women. The 1st trimester of the pregnancy was more symptomatic for HAE-nC1-INH women. Considering the strong relevance of estrogens in HAE-nC1-INH, pregnancy could worsen the course of disease.

Vacina COVID-19 em pacientes com urticária ­ Posicionamento do Departamento Científico de Urticária da Associação Brasileira de Alergia e Imunologia (ASBAI) / COVID-19 vaccine in patients with urticaria ­ Position statement of the Scientific Department of Urticaria of the Brazilian Association of Allergy and Immunology (ASBAI)

Com o início do programa de vacinação contra a COVID-19 no Brasil, surgiu uma série de questionamentos relacionados ao uso dos imunizantes em pacientes com doenças imunoalérgicas. Neste documento, o Departamento Científico de Urticária da Associação Brasileira de Alergia e Imunologia (ASBAI) se posiciona revisando as principais dúvidas relacionadas à imunização para COVID-19 em pacientes com urticária.

As the COVID-19 vaccination program started in Brazil, many questions have arisen regarding the use of vaccines in patients with immune-allergic diseases. In this document, the Scientific Department of Urticaria of the Brazilian Association of Allergy and Immunology takes a stand by reviewing the main queries regarding COVID-19 immunization in patients with urticaria.

Urticária e a COVID-19 / Urticaria and COVID-19

A pandemia de COVID-19 afetou drasticamente a vida de todos ao redor do planeta, interferindo também na forma de atuarmos como médicos e especialistas. Neste artigo revisamos aspectos importantes da infecção pelo novo coronavírus e sua relação com a urticária.

The COVID-19 pandemic has dramatically affected people's lives around the world and has interfered with how we act as physicians and specialists. In this paper, we review important aspects of the new coronavirus infection and its connection with urticaria.

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.

Hereditary angioedema: how to approach it at the emergency department?

Angioedema attacks are common causes of emergency care, and due to the potential for severity, it is important that professionals who work in these services know their causes and management. The mechanisms involved in angioedema without urticaria may be histamine- or bradykinin-mediated. The most common causes of histamine-mediated angioedema are foods, medications, insect sting and idiopathic. When the mediator is bradykinin, the triggers are angiotensin-converting enzyme inhibitors and factors related to acquired angioedema with deficiency of C1-inhibitor or hereditary angioedema, which are less common, but very important because of the possibility of fatal outcome. Hereditary angioedema is a rare disease characterized by attacks of edema that affect the subcutaneous tissue and mucous membranes of various organs, manifesting mainly by angioedema and abdominal pain. This type of angioedema does not respond to the usual treatment with epinephrine, antihistamines and corticosteroids. Thus, if not identified and treated appropriately, these patients have an estimated risk of mortality from laryngeal edema of 25% to 40%. Hereditary angioedema treatment has changed dramatically in recent years with the development of new and efficient drugs for attack management: plasma-derived C1 inhibitor, recombinant human C1-inhibitor, bradykinin B2 receptor antagonist (icatibant), and the kallikrein inhibitor (ecallantide). In Brazil, plasma-derived C1 inhibitor and icatibant have already been approved for use. Proper management of these patients in the emergency department avoids unnecessary surgery and, especially, fatal outcomes.

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.

The global impact of the COVID-19 pandemic on the management and course of chronic urticaria.

INTRODUCTION: The COVID-19 pandemic dramatically disrupts health care around the globe. The impact of the pandemic on chronic urticaria (CU) and its management are largely unknown. AIM: To understand how CU patients are affected by the COVID-19 pandemic; how specialists alter CU patient management; and the course of CU in patients with COVID-19. MATERIALS AND METHODS: Our cross-sectional, international, questionnaire-based, multicenter UCARE COVID-CU study assessed the impact of the pandemic on patient consultations, remote treatment, changes in medications, and clinical consequences. RESULTS: The COVID-19 pandemic severely impairs CU patient care, with less than 50% of the weekly numbers of patients treated as compared to before the pandemic. Reduced patient referrals and clinic hours were the major reasons. Almost half of responding UCARE physicians were involved in COVID-19 patient care, which negatively impacted on the care of urticaria patients. The rate of face-to-face consultations decreased by 62%, from 90% to less than half, whereas the rate of remote consultations increased by more than 600%, from one in 10 to more than two thirds. Cyclosporine and systemic corticosteroids, but not antihistamines or omalizumab, are used less during the pandemic. CU does not affect the course of COVID-19, but COVID-19 results in CU exacerbation in one of three patients, with higher rates in patients with severe COVID-19. CONCLUSIONS: The COVID-19 pandemic brings major changes and challenges for CU patients and their physicians. The long-term consequences of these changes, especially the increased use of remote consultations, require careful evaluation.

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.

Hereditary angioedema: how to approach it at the emergency department? / Angioedema hereditário: como abordar na emergência?

ABSTRACT Angioedema attacks are common causes of emergency care, and due to the potential for severity, it is important that professionals who work in these services know their causes and management. The mechanisms involved in angioedema without urticaria may be histamine- or bradykinin-mediated. The most common causes of histamine-mediated angioedema are foods, medications, insect sting and idiopathic. When the mediator is bradykinin, the triggers are angiotensin-converting enzyme inhibitors and factors related to acquired angioedema with deficiency of C1-inhibitor or hereditary angioedema, which are less common, but very important because of the possibility of fatal outcome. Hereditary angioedema is a rare disease characterized by attacks of edema that affect the subcutaneous tissue and mucous membranes of various organs, manifesting mainly by angioedema and abdominal pain. This type of angioedema does not respond to the usual treatment with epinephrine, antihistamines and corticosteroids. Thus, if not identified and treated appropriately, these patients have an estimated risk of mortality from laryngeal edema of 25% to 40%. Hereditary angioedema treatment has changed dramatically in recent years with the development of new and efficient drugs for attack management: plasma-derived C1 inhibitor, recombinant human C1-inhibitor, bradykinin B2 receptor antagonist (icatibant), and the kallikrein inhibitor (ecallantide). In Brazil, plasma-derived C1 inhibitor and icatibant have already been approved for use. Proper management of these patients in the emergency department avoids unnecessary surgery and, especially, fatal outcomes.

RESUMO As crises de angioedema são causas comuns de atendimentos nas emergências, e devido ao potencial de gravidade, é importante que os profissionais que atuam nesses serviços conheçam suas causas e abordagem. Os mecanismos envolvidos no angioedema sem urticas podem ser histaminérgicos ou mediados por bradicinina. As causas mais comuns de angioedema mediado por histamina são alimentos, medicamentos, ferroada de insetos e idiopática. Quando o mediador é a bradicinina, os desencadeantes são os inibidores da enzima conversora de angiotensina e fatores relacionados ao angioedema adquirido com deficiência do inibidor de C1 ou angioedema hereditário que são menos comuns, mas muito importantes pela possibilidade de desfecho fatal. O angioedema hereditário é uma doença rara, caracterizada por crises de edema que acometem o tecido subcutâneo e mucosas de vários órgãos, manifestando-se principalmente por crises de angioedema e dor abdominal. Esse tipo de angioedema não responde ao tratamento usual com adrenalina, anti-histamínicos e corticosteroides. Assim, se não identificados e tratados adequadamente, esses pacientes têm risco de morte por edema de laringe estimado em 25% a 40%. O tratamento do angioedema hereditário mudou drasticamente nos últimos anos, com o desenvolvimento de novos e eficientes fármacos para as crises: inibidor de C1 derivado de plasma, inibidor de C1 recombinante humano, antagonista do receptor B2 da bradicinina (icatibanto) e o inibidor da calicreína (ecalantide). No Brasil, até o momento, estão liberados para uso o inibidor de C1 derivado de plasma e o icatibanto. O manejo correto desses pacientes na emergência evita cirurgias desnecessárias e, principalmente, desfechos fatais.

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.