Clinical features of hereditary angioedema and warning signs (H4AE) for its identification.

OBJECTIVES: The study describes a case series of hereditary angioedema with C1 Inhibitor Deficiency (C1INH-HAE) in order to corroborate six clinical warning signs "HAAAAE (H4AE)" to enable early identification of this disease. METHODS: The authors analyzed the C1INH-HAE cohort to analyze the clinical aspects of the present study's patients and corroborate the six clinical warning signs of the Hereditary Angioedema Brazilian Guidelines. Data regarding demographics, the onset of disease, time to diagnosis, frequency of attacks per year, organs involved, triggers, crisis duration and their outcomes, and disease treatment were collected. Then the authors developed an acronym, H4AE, to help healthcare professionals remember the warning signs. RESULTS: The authors included 98 patients in the study, with a mean age of 38.1 years, 67.3% being female, and 75.3% with a family history of HAE. HAE diagnosis was delayed, on average, 13.7 years after its initial manifestation. Exploratory laparotomy was reported by 26.9%, and orotracheal intubation by 21.3% of the present study's patients; 61.3% and 30.3% of them were admitted at least once in the hospital and in the intensive care unit, respectively. The authors constructed an acronym "H4AE" with the six warning signs of HAE: Hereditary, recurrent Angioedema, Abdominal pain, Absence of urticaria, Absence of response to antihistamines, Estrogen association. CONCLUSION: C1INH-HAE is still underdiagnosed and associated with high morbidity. The study showed clinical features of this disease, corroborating the warning signs, which may be useful in raising awareness and improving the diagnosis of C1INH-HAE. The authors suggest the acronym "H4AE" to remind the warning signs.

Clinical features of hereditary angioedema and warning signs (H4AE) for its identification

Abstract Objectives The study describes a case series of hereditary angioedema with C1 Inhibitor Deficiency (C1INH-HAE) in order to corroborate six clinical warning signs "HAAAAE (H4AE)" to enable early identification of this disease. Methods The authors analyzed the C1INH-HAE cohort to analyze the clinical aspects of the present study's patients and corroborate the six clinical warning signs of the Hereditary Angioedema Brazilian Guidelines. Data regarding demographics, the onset of disease, time to diagnosis, frequency of attacks per year, organs involved, triggers, crisis duration and their outcomes, and disease treatment were collected. Then the authors developed an acronym, H4AE, to help healthcare professionals remember the warning signs. Results The authors included 98 patients in the study, with a mean age of 38.1 years, 67.3% being female, and 75.3% with a family history of HAE. HAE diagnosis was delayed, on average, 13.7 years after its initial manifestation. Exploratory laparotomy was reported by 26.9%, and orotracheal intubation by 21.3% of the present study's patients; 61.3% and 30.3% of them were admitted at least once in the hospital and in the intensive care unit, respectively. The authors constructed an acronym "H4AE" with the six warning signs of HAE: Hereditary, recurrent Angioedema, Abdominal pain, Absence of urticaria, Absence of response to antihistamines, Estrogen association. Conclusion C1INH-HAE is still underdiagnosed and associated with high morbidity. The study showed clinical features of this disease, corroborating the warning signs, which may be useful in raising awareness and improving the diagnosis of C1INH-HAE. The authors suggest the acronym "H4AE" to remind the warning signs.

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.

Rinite em pré-escolares / Rhinitis in preschool children

A rinite no pré-escolar configura um grande desafio diagnóstico e terapêutico, tanto para pediatras, como para especialistas. Os poucos dados existentes nesta faixa etária, além da sobreposição dos sintomas também comuns às doenças respiratórias virais, tornam o diagnóstico de rinite extremamente raro e/ou frequentemente ignorado. A melhor compreensão e identificação da rinite nos pré-escolares pode ajudar a melhorar a qualidade de vida destes pacientes, através da instituição do diagnóstico e tratamento corretos. Além disso, o diagnóstico mais precoce, possivelmente possibilitará caracterizar melhor a história natural da rinite, comorbidades, fatores de risco e o acompanhamento do desenvolvimento dos diferentes fenótipos da rinite ao longo da vida.

Rhinitis in preschool children is a major diagnostic and therapeutic challenge for both pediatricians and specialists. The diagnosis of rhinitis is extremely rare and/or often ignored in this specific age group, due to the few data available and the overlapping of symptoms common to viral respiratory diseases. A better understanding and identification of rhinitis in preschool children could improve the quality of life of these patients by making diagnosis more accurate and delivering appropriate treatment. In addition, an earlier diagnosis may help better understand the natural history of rhinitis, comorbidities, risk factors and follow-up of different phenotypes throughout life.

Avaliação do fenótipo atópico nos pacientes com DREA / Evaluation of atopic phenotype in patients with DREA

Introdução: A doença respiratória exacerbada por anti-inflamatórios (DREA) é uma síndrome bem caracterizada, composta por asma, polipose nasal e intolerância a aspirina e anti-inflamatórios não esteroidais (AINEs). Apesar de já bem definida, há uma heterogeneidade entre a população de pacientes com diagnóstico de DREA. O objetivo desse trabalho foi avaliar o fenótipo atópico nos pacientes com DREA. Métodos: Foi realizado um estudo retrospectivo com pacientes com DREA acompanhados em um serviço terciário. Esses pacientes foram classificados em dois grupos: atópicos e não atópicos. Foram avaliados também dados como gravidade da asma, AINEs envolvidos na reação, e IgE sérica total. Resultados: Foram analisados 70 pacientes, destes 55 (78,6%) eram mulheres. A média de idade era de 54 anos. Do total de pacientes, 32 (45,7%) eram atópicos. Os pacientes atópicos apresentavam média de início de asma mais precoce (22 anos) e maior tempo de doença (31 anos) do que os não atópicos. A média de IgE sérica total era maior nos atópicos (742,1 UI/mL). No grupo dos pacientes com DREA e atopia, a pesquisa de IgE sérica específica mostrou-se positiva para os ácaros em 90,6% dos pacientes. A maioria dos pacientes atópicos (71%) relatava reação a múltiplos AINEs. Os principais medicamentos relacionados às exacerbações respiratórias nos pacientes com DREA foram: AAS em 72,1% dos casos; dipirona em 61,8%; diclofenaco em 45,6%; e cetoprofeno e ibuprofeno em 27,9% dos casos cada um. Conclusões: Existem diferenças entre os pacientes com DREA conforme a presença ou não de atopia. Os atópicos apresentam início de sintomas mais precoce, maior tempo de duração de asma, necessitam de mais medicação para controle e apresentam hipersensibilidade a um número maior de AINEs, sendo que o principal medicamento causador de sintomas também varia entre os dois grupos.

Introduction: Aspirin-exacerbated respiratory disease (AERD) is a well characterized syndrome in which asthma, nasal polyposis, and intolerance to aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) coexist. Even though it is well defined, the population of patients diagnosed with AERD is very heterogeneous. The aim of this study was to evaluate atopic phenotype in patients with AERD. Methods: A retrospective study was performed with patients with AERD followed at a tertiary hospital. These patients were classified into two groups: atopic and non-atopic. Clinical characteristics and data such as asthma severity, NSAIDs involved in the reaction and total serum IgE were also evaluated. Results: Seventy patients were analyzed, of which 55 (78.6%) were women. Mean age was 54 years. Of the total sample, 32 (45.7%) were atopic. Atopic patients had a lower mean age at the onset of asthma (22 years) and presented a longer mean disease duration (31 years) than non-atopic patients. Mean total serum IgE was higher in atopic patients (742.1 IU/ mL). In the group with AERD and atopy, the specific serum IgE test was positive for mites in 90.6% of the patients. Most atopic patients (71%) reported reaction to multiple NSAIDs. The main drugs related to respiratory exacerbations in patients with AERD were: aspirin in 72.1% of cases; dipyrone in 61.8%; diclofenac in 45.6%; ketoprofen and ibuprofen in 27.9% each. Conclusions: There are differences between patients with AERD according to the presence or absence of atopy. Atopic patients have an earlier onset of symptoms and a longer duration of asthma, they require more medication to control the condition and are hypersensitive to a greater number of NSAIDs; the drug that most commonly triggered symptoms also differed between the two groups.

Brazilian Guidelines for Hereditary Angioedema Management - 2017 Update Part 1: Definition, Classification and Diagnosis.

Hereditary angioedema is an autosomal dominant disease characterized by recurrent angioedema attacks with the involvement of multiple organs. The disease is unknown to many health professionals and is therefore underdiagnosed. Patients who are not adequately diagnosed and treated have an estimated mortality rate ranging from 25% to 40% due to asphyxiation by laryngeal angioedema. Intestinal angioedema is another important and incapacitating presentation that may be the main or only manifestation during an attack. In this article, a group of experts from the "Associação Brasileira de Alergia e Imunologia (ASBAI)" and the "Grupo de Estudos Brasileiro em Angioedema Hereditário (GEBRAEH)" has updated the Brazilian guidelines for the diagnosis and treatment of hereditary angioedema.

Atopy Is Associated with Age at Asthma Onset in Elderly Patients.

BACKGROUND: Asthma in the elderly population (60 years of age and older) is frequently underdiagnosed, as well as atopy. Atopy, although more prevalent in younger patients, can be a major cause of asthma in the elderly. Chronic obstructive pulmonary disease (COPD) and cardiovascular disease are common differential diagnoses, especially in elderly smokers. OBJECTIVE: The objective of this study was to assess atopy and comorbidities in elderly patients with asthma. METHODS: This was an observational and retrospective study involving elderly asthmatic patients followed up at a tertiary center. Patients were assessed for severity of asthma, frequency of atopy, and frequency of comorbidities concomitant with asthma. Then, they were classified according to their age at asthma onset and the groups compared with each other for atopy, spirometric parameters, and comorbidities. RESULTS: This study included 243 elderly asthmatic patients, 71.8% of them presenting severe disease and 82.3% forced expiratory volume in 1 second (FEV1) < 80%. Gastroesophageal reflux disease, obesity, and asthma-COPD overlap syndrome were observed, respectively, in 64%, 37%, and 13% of these patients. Atopy was observed in 63%, mainly in those with early onset disease, and its frequency decreased as the age of asthma onset increased (P < .05). Total serum IgE was higher for allergic patients and FEV1 values were lower for patients with long-term asthma. Aspirin-exacerbated respiratory disease was more frequent in patients with nonallergic asthma. CONCLUSIONS: Most elderly asthmatic patients followed up in our tertiary center were atopic and higher values of total serum IgE suggest atopy. Atopy was inversely correlated with age of asthma onset. The diagnosis of allergic asthma in the elderly population is essential to treat patients more properly, improving their quality of life and decreasing asthma morbidity and mortality.

Brazilian Guidelines for Hereditary Angioedema Management - 2017 Update Part 1: Definition, Classification and Diagnosis

Hereditary angioedema is an autosomal dominant disease characterized by recurrent angioedema attacks with the involvement of multiple organs. The disease is unknown to many health professionals and is therefore underdiagnosed. Patients who are not adequately diagnosed and treated have an estimated mortality rate ranging from 25% to 40% due to asphyxiation by laryngeal angioedema. Intestinal angioedema is another important and incapacitating presentation that may be the main or only manifestation during an attack. In this article, a group of experts from the "Associação Brasileira de Alergia e Imunologia (ASBAI)" and the "Grupo de Estudos Brasileiro em Angioedema Hereditário (GEBRAEH)" has updated the Brazilian guidelines for the diagnosis and treatment of hereditary angioedema.

Allergic and Nonallergic Asthma Have Distinct Phenotypic and Genotypic Features.

BACKGROUND: Identification of asthma phenotypes enables a better understanding and management of this heterogeneous disease. Studies have reported associations between human leukocyte antigens (HLA) and asthma in different populations, but the results have been inconclusive and they have rarely considered the distinct disease phenotypes. Our objective was to characterize allergic and nonallergic asthma phenotypes and evaluate possible associations with the HLA system. METHODS: A total of 109 patients with asthma were prospectively followed during 2 years. They were divided into 2 groups, i.e., allergic and nonallergic asthma, according to their clinical history and skin prick test and serum-specific immunoglobulin E (IgE) results. The control group comprised 297 deceased donors of solid organs. Patients' features and HLA class I and II genotypes were assessed and compared. RESULTS: This study showed different features between asthma phenotypes. Nonallergic patients were older at the onset of asthma symptoms and had a higher rate of intolerance to nonsteroidal anti-inflammatory drugs. Allergic patients had higher total serum IgE levels, reported atopic dermatitis and rhinoconjunctivitis more frequently, and, unexpectedly, had a greater disease severity. New associations between the HLA genotypes and allergic and nonallergic asthma were identified. The HLA-B*42, HLA-C*17, HLA-DPA1*03, and HLA-DPB1*105 genotypes were associated with allergic asthma and the HLA-B*48 genotype with the nonallergic phenotype. The presence of the haplotype HLA-DPA1*03 DQA*05 was associated with allergic asthma, and the presence of HLA-DPA1*03 and the absence of HLA-DQA*05 with nonallergic asthma. CONCLUSIONS: Allergic and nonallergic asthma have distinct phenotypic and genotypic features. New associations between asthma phenotypes and HLA class I and II were identified.

Asma alérgica e não alérgica apresentam diferentes características fenotípicas e genotípicas / Allergic and non-allergic asthma have different phenotypic and genotypic characteristics

Objetivo: A identificação dos fenótipos da asma permite uma melhor compreensão e abordagem desta doença heterogênea. Muitos estudos têm demonstrado associação entre os antígenos leucocitários humanos (HLA) e asma em diversas populações, porém os resultados são inconclusivos e raramente consideram uma doença com diferentes fenótipos. O objetivo deste estudo foi caracterizar os fenótipos alérgico e não alérgico da asma e avaliar possíveis associações com o sistema HLA. Métodos: Um total de 190 pacientes com asma foram prospectivamente acompanhados durante dois anos. Foram divididos em dois grupos, asma alérgica e não alérgica, de acordo com a história clínica e os resultados do teste cutâneo de puntura e da pesquisa da IgE sérica específica. O grupo controle foi composto por 297 doadores falecidos de órgãos sólidos. As características de cada grupo e a tipificação dos HLA classe I e II foram avaliadas e comparadas. Resultados: O estudo mostrou diferentes características entre os fenótipos estudados. Os pacientes com asma não alérgica relataram uma idade mais tardia de início dos sintomas da doença e maior frequência de história sugestiva de intolerância aos anti-inflamatórios não esteroidais. O grupo asma alérgica apresentaram IgE sérica total elevada, presença de dermatite atópica e rinoconjuntivite mais frequente e, inesperadamente, maior gravidade da doença. Novas associações entre os genótipos HLA e os fenótipos alérgico e não alérgico da asma foram identificados. Os genótipos HLA-B*42, HLA-C*17, HLA-DPA1*03 e HLA-DPB1*105 foram associados com a asma alérgica, e o HLA-B*48 com o fenótipo não alérgico. A presença do haplótipo HLA-DPA1*03 DQA*05 foi associado com asma alérgica, e a presença do HLA-DPA1*03 e ausência do HLA-DQA*05 com a asma não alérgica. Conclusões: A asma alérgica e não alérgica apresentaram diferentes características fenotípicas e genotípicas. Novas associações entre os fenótipos e o sistema HLA classe I e II foram identificadas.

Objective: The identification of asthma phenotypes allows a better understanding and management of this heterogeneous disease. Studies have reported associations between human leukocyte antigens (HLA) and asthma in different populations, but results have been inconclusive and rarely take into consideration the distinct disease phenotypes. The objectives of this study were to characterize allergic and non-allergic asthma phenotypes and to evaluate possible associations with the HLA system. Methods: A total of 190 patients with asthma were prospectively followed during two years. They were divided into two groups, allergic and non-allergic asthma, according to clinical history and the results of skin prick testing and serum-specific IgE measurement. The control group comprised 297 deceased donors of solid organs. The characteristics of each group and HLA class I and II genotypes were assessed and compared. Results: The study revealed different characteristics between the phenotypes studied. Nonallergic patients were older at the onset of asthma symptoms and had a higher rate of history of intolerance to non-steroidal antiinflammatory drugs. Allergic patients showed higher total serum IgE levels, reported atopic dermatitis and rhinoconjunctivitis more frequently, and, unexpectedly, showed greater disease severity. New associations between HLA genotypes and the allergic/non-allergic asthma phenotypes were identified. HLA-B*42, HLA-C*17, HLADPA1* 03, and HLA-DPB1*105 genotypes were associated with allergic asthma, and HLA-B*48, with the non-allergic phenotype. The presence of haplotype HLA-DPA1*03 DQA*05 was associated with allergic asthma, and the presence of HLA-DPA1*03 and absence of HLA-DQA*05, with non-allergic asthma. Conclusion: Allergic and non-allergic asthma have distinct phenotypic and genotypic characteristics. New associations between asthma phenotypes and HLA class I and II were identified.

United airway disease: current perspectives.

Upper and lower airways are considered a unified morphological and functional unit, and the connection existing between them has been observed for many years, both in health and in disease. There is strong epidemiologic, pathophysiologic, and clinical evidence supporting an integrated view of rhinitis and asthma: united airway disease in the present review. The term "united airway disease" is opportune, because rhinitis and asthma are chronic inflammatory diseases of the upper and lower airways, which can be induced by allergic or nonallergic reproducible mechanisms, and present several phenotypes. Management of rhinitis and asthma must be jointly carried out, leading to better control of both diseases, and the lessons of the Allergic Rhinitis and Its Impact on Asthma initiative cannot be forgotten.